February 6th 2020: CRISPR-Edited Immune Cells Can Survive and Thrive After Infusion into Cancer Patients

Genetically-edited immune cells can persist, thrive, and function months after a cancer patient receives them, according to new data published by researchers from the Abramson Cancer Center of the University of Pennsylvania. The team showed cells removed from patients and brought back into the lab setting were able to kill cancer months after their original manufacturing and infusion. Further analysis of these cells confirmed they were successfully edited in three specific ways, marking the first-ever sanctioned investigational use of multiple edits to the human genome. This is the first U.S. clinical trial to test the gene editing approach in humans, and the publication of this new data today in Science follows on the initial report last year that researchers were able to use CRISPR/Cas9 technology to successfully edit three cancer patients’ immune cells. The TCSL was integral to this work, reflected in the fact that six members of the TCSL are among the authors, and eleven more members of the laboratory were acknowledged for experimental support. Penn is conducting the ongoing study in cooperation with the Parker Institute for Cancer Immunotherapy and Tmunity Therapeutics. Some of the media coverage is linked below: Penn Medicine News ReleaseReuters Health • WiredGizmodoDaily Mail HealthTimes of London • HealthDay News • Science • New Scientist • The ScientistScience NewsScience Blogs • Genetic Engineering & Biotechnology News • International Business Times • HealthlineNew Atlas • Technology NetworksTechnology Review • AFP via MSN Lifestyle • ClinicalOMICSArchyNewsyChemistry WorldLa Vanguardia (Spain)Diario Medico (Spain)El Pais (Spain) • Publico (Portugal)

November 6th 2019: Crispr Takes Its First Steps in Editing Genes to Fight Cancer

Doctors have for the first time in the United States tested a powerful gene-editing technique in people with cancer. The test, meant to assess only safety, was a step toward the ultimate goal of editing genes to help a patient’s own immune system to attack cancer. The editing was done by the DNA-snipping tool Crispr. The procedure was feasible and safe, early results indicate, but whether it is fighting the disease is unclear. Only three patients have been treated so far, and the longest follow-up is nine months. All three patients are in their 60s, with very advanced cancers that had progressed despite standard treatments like surgery, radiation and chemotherapy. “The good news is that all of them are alive,” said Dr. Edward A. Stadtmauer, the section chief of hematologic malignancies at the University of Pennsylvania Abramson Cancer Center. He added, “The best response we’ve seen so far is stabilization of their disease.” The research was paid for by the Parker Institute for Cancer Immunotherapy and the company Tmunity. Some members of the research team, but not Dr. Stadtmauer, are equity holders in Tmunity, as is the University of Pennsylvania. The findings have not yet been published in a medical journal, but will be presented next month at a meeting of the American Society of Hematology, and posted online on Wednesday. New York Times Article

March 5th 2019: Penn Researchers Receive Three of Ten National Clinical Research Achievement Awards

PHILADELPHIA—Three researchers from the Perelman School of Medicine at the University of Pennsylvania are among the recipients of the 2019 Clinical Research Achievement Awards from the Clinical Research Forum, which recognizes the ten most outstanding clinical research accomplishments in the United States during the preceding twelve months.

Researchers from all ten winning studies will be recognized at a dinner and reception at the National Press Club on March 5th in Washington, D.C. The Penn awardees are Lindsey A. George, MD, an assistant professor of Pediatrics at Penn and an attending physician in the division of Hematology at Children's Hospital of Philadelphia, for the first gene therapy trial to report a clinical cure for hemophilia B patients; Courtney A. Schreiber, MD, an associate professor of Obstetrics and Gynecology, for the only randomized clinical trial to date to test the efficacy of miscarriage management medications; and Joseph A. Fraietta, PhD, an assistant professor of Microbiology, for a study predicting the response of patients with chronic lymphocytic leukemia to chimeric antigen receptor (CAR) T cell therapy.

Penn Medicine Press Release

October 22nd 2018: Abramson Cancer Center Receives $10.7 Million to Study CAR T Cells in Solid Tumors

PHILADELPHIA – A new program project grant from the National Cancer Institute (NCI) will fund research by the Translational Center of Excellence for Lung Cancer Immunology at the Abramson Cancer Center of the University of Pennsylvania to improve the effectiveness of chimeric antigen receptor (CAR) T cell therapy at fighting solid tumors. Specifically, the program will evaluate approaches in lung cancer and mesothelioma. The $10.7 million grant will support the research for the next five years.

“Although CAR T cells have been revolutionized the treatment of leukemia and bone marrow cancers, we have not yet had the same success in treating solid tumors like lung cancer,” said the principal investigator of the grant, Steven M. Albelda, MD, the William Maul Measey Professor of Medicine at Penn and a member of the Center for Cellular Immunotherapies in the Abramson Cancer Center. “The goal of this program project is to solve this problem, and we’re grateful to the NCI for supporting our efforts to expand this approach to more patients around the world.” The overall grant will include three interrelated projects, all of which will focus on exploring the ability of CAR T cells to stimulate other immune cells like dendritic cells and T cells to respond against the tumor – known the “bystander effect” – in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). The first project is a clinical trial with newly designed, highly potent anti-mesothelin CAR T cells. This project will also include a future trial to evaluate the safety and activity of CAR T cells engineered to engage the tumor “support structure” by targeting a protein called fibroblast activation protein (FAP), which is present on the supportive fibroblasts in the tumor. The results of the first two trials will also be used to design a third trial in the future, which will also be supported by this grant. Initial trials were conducted in collaboration with Novartis, but future trials with the anti-mesothelin CAR T cells will be conducted solely by Penn. The second project will involve tracking CAR T cells and their effects in patients. It will attempt to answer the question of how long these CAR T cells persist and where they go, as well as whether they can activate other T cell responses. The third project will study ways to improve the effectiveness of CARs in animal models. Since not all the tumor cells will have the target of the CARs, it will be important to find ways to trigger a patient’s own immune system to also attack the tumor cells the CARs will miss, another facet of the “bystander effect”. This project will also explore ways in which CARs can be combined with other therapies to enhance efficacy. “The stakes of these projects are incredibly high. Achieving the success rates for CAR T therapy in solid tumors that we’ve already seen in leukemia and lymphoma would be a major paradigm shift in the treatment of these cancers,” Albelda said. Other Penn researchers involved in this project include Charu Aggarwal, Beatriz Carreno, Andrew R. Haas, Wei-Ting Hwang, Carl June, Simon Lacey, Corey Langer, Gerald Linette, Leslie Litzky, and Ellen Puré.Penn Medicine Press Release

October 1st 2018: Penn Discovers New, Rare Mechanism for ALL to Relapse after CAR T Cell Therapy

PHILADELPHIA – A single leukemia cell, unknowingly engineered with the leukemia-targeting chimeric antigen receptor (CAR) lentivirus and infused back into a patient, was able to reproduce and cause a deadly recurrence of pediatric B-cell acute lymphoblastic leukemia (ALL).

New research from the Abramson Cancer Center of the University of Pennsylvania found that in one patient, the CAR lentivirus that would usually enter a T cell to teach it to hunt cancer also ended up binding with a leukemic cell. The presence of the CAR on the leukemic cell may have given that cell the ability to hide from the therapy by masking CD19, the protein that CARs target to kill cancer. Leukemic cells without CD19 are resistant to CAR T therapy, so this single cell led to the patient’s relapse. Nature Medicine published the findings today. Penn co-authors of this study include Jun Xu, Joseph A. Fraietta, Tyler J. Reich, David E. Ambrose, Michael Klichinsky, Olga Shestova, Prachi R. Patel, Irina Kulikovskaya, Farzana Nazimuddin, Vijay G. Bhoj, Bruce L. Levine, Christopher L. Nobles, Frederic D. Bushman, Regina M. Young, John Scholler, Saar I. Gill, Carl H. June, and Simon F. Lacey. CHOP co-authors include David M. Barrett, Shannon L. Maude, and Stephan A. Grupp. Novartis co-authors include Elena J. Orlando and Hans Bitter. Nature Medicine Paper

Coverage: Penn Medicine News Release New York Times Article STAT News Article

June 27th 2018: Penn makes third big biotech bet, helping to raise $53M for Carisma

Carisma Therapeutics Inc., a cancer-fighting Philadelphia biotech company formerly known as Carma Therapeutics, said Wednesday that the University of Pennsylvania has joined a list of investors who together have committed $53 million to speed its cancer cell therapies to market.

Penn is joining previously announced private-sector Carisma investors led by Boston-based AbbVie Ventures. This makes Carisma the third small firm juiced by investments of up to $5 million each from the University of Pennsylvania’s new $50 million biotech investment program. The university has also bought into Carl June’s Tmunity and Steven Nichtberger’s Tycho Therapeutics, and is seeking to back at least 10 firms total in a pilot investing program approved by board members in April. Coverage: Endpoints Philly.com FierceBiotech Technical.ly

May 30th 2018: Nature Article from PDCS: Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells

"The receptor, known as a chimaeric antigen receptors (CAR), directs the engineered cell, called a CAR T cell, to the patient’s tumour when the cell is transferred back into the body. This therapy can be highly effective for tumours that express the protein CD19, such as B-cell acute leukaemias and large-cell lymphomas. However, some people do not respond to CAR T cells, and efforts to optimize this therapy are ongoing. In a paper in Nature, Fraietta et al. report the fortuitous identification of a gene that positively affected one person’s response to treatment with CAR T cells."

Link to Nature paper Link to Nature News and Views Commentary on article Penn Medicine News Release Philly Magazine news article

May 1st 2018: Kymriah® (tisagenlecleucel) receives second FDA approval to treat patients with large B-cell lymphoma


Novartis today announced the US Food and Drug Administration (FDA) has approved Kymriah® (tisagenlecleucel) suspension for intravenous infusion for its second indication – the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.


The U.S. Food and Drug Administration (FDA) has expanded approval for a personalized cellular therapy developed at the University of Pennsylvania’s Abramson Cancer Center, this time for the treatment of adult patients with relapsed or refractory large B-Cell lymphoma after two or more lines of systemic therapy. Today’s approval includes treatment of diffuse large B-cell lymphoma (DLBCL) – the most common form of non-Hodgkin’s lymphoma – as well as high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. The approval was granted today to Novartis for the chimeric antigen receptor (CAR) T-cell therapy Kymriah® (tisagenlecleucel, formerly CTL019), making it the second indication for the nation’s first personalized cellular therapy for cancer.

Novartis Press Release FiercePharma article Penn Medicine Press Release


April 30th 2018: T Cell Biomarker Predicts Which CLL Patients Will Respond to CAR T Cell Therapy

Penn study suggests response may depend on quality of patients’ existing T cells before infusion

PHILADELPHIA – Penn Medicine researchers may have found the reason why some patients with advanced chronic lymphocytic leukemia (CLL) don’t respond to chimeric antigen receptor (CAR) T cell therapy, and the answer is tied to how primed patients’ immune systems are before the therapy is administered. While 80 percent of patients with advanced acute lymphoblastic leukemia (ALL) treated with the CAR T cell therapy now known as Kymriah™ have a dramatic response, only 26 percent of CLL patients respond to it in clinical trials. A new study from the Abramson Cancer Center of the University of Pennsylvania, published today in Nature Medicine, shows that CLL patients possessing a subset of vital, healthier T cells prior to CAR T cell therapy had a partial or complete clinical response to the treatment, while those lacking enough of those T cells did not respond. These healthier “early memory” T cells were marked by the expression of CD8 and CD27, as well as the absence of CD45RO. The findings show the potential to improve responses by enhancing a patient’s immune cells with emerging cell manufacturing techniques before CAR T cell therapy.

What’s more, the team – which was led by senior author J. Joseph Melenhorst, PhD and first author Joseph A. Fraietta, PhD, both faculty in the department of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine and of Penn’s Center for Cellular Immunotherapies, and included a multidisciplinary team from Penn and Novartis – also validated this signature in a separate, small group of patients and predicted with 100 percent accuracy who would experience complete remission. Penn Medicine Press Release Nature Medicine Article Philadelphia Inquirer article


April 2018: Carl June named as one of TIME's 100 most influential people of 2018.

Article Penn Medicine Press Release

February 2018: Nicola Mason's group at Penn Vet

Dr. Nicola Mason B.Vet.Med., PhD, DACVIM, associate professor at Penn Vet, runs a translational research laboratory that focuses on ways to train the immune system to recognize and kill cancers in veterinary species. CCI and PDCS have been privileged to collaborate with her group over the last few years. Mason Lab Webpage

A TIAA-sponsored video profiles Dr. Mason and her work: Dog Years


January 23rd 2018: Allied with Penn, Tmunity’s cell therapy pioneers bag $100M mega-round to back a breakthrough quest on CAR-T, CRISPR

Novartis vet Usman “Oz” Azam and Penn researcher Carl June are two of the ultimate insiders in the CAR-T revolution. They each played prominent roles in advancing Novartis’ breakthrough therapy Kymriah to an historic first-ever approval. They are now allied in an attempt to do it all much, much better with next-gen tech which just attracted a $100 million mega-round from an unconventional group of global globiotech investors. And after staying quiet for more than a year, they’re already in the clinic with two open programs, playing a key role co-funding a cutting-edge cell therapy study at Penn using CRISPR to modify immune cells.

ENDPOINTS News FierceBiotech Forbes article Philadelphia Business Journal

January 17th 2018: U.S. doctors plan to treat cancer patients using CRISPR

The first human test in the U.S. involving the gene-editing tool CRISPR could begin at any time and will employ the DNA cutting technique in a bid to battle deadly cancers. Doctors at the University of Pennsylvania say they will use CRISPR to modify human immune cells so that they become expert cancer killers, according to plans posted this week to a directory of ongoing clinical trials. The study will enroll up to 18 patients fighting three different types of cancer—multiple myeloma, sarcoma, and melanoma—in what could become the first medical use of CRISPR outside China, where similar studies have been under way. Coverage at MIT Technology Review and in the Wall Street Journal

November 15th 2017: An interview with Carl June: Dr. Carl June's CAR-T Cell Journey and the Cancer Treatment Revolution

FDA approval of the breakthrough CAR-T cell therapy for cancer brings the first approved gene therapy treatment to the United States. It reprograms the body's own immune system to recognize and kill cancer cells. The therapy initially called CAR-T cell immunotherapy and now named Kymriah by Novartis, is approved to treat children and young adults with a recurrent form of the blood cancer called acute lymphoblastic leukemia (ALL). Dr. Carl June of University of Pennsylvania, is one of the pioneers of CAR-T cell research and leads the team responsible for the historic FDA approval. We are discussing Dr. Junes CAR-T cell journey to understand nuances of the new therapy. The discussion will also bring to focus the opportunity that these engineered immune cells present to cancer treatment and possible use in treatment of other cancers. Link to CureTalks page with audio and transcript of conversation

PHILADELPIA October 21 2017:Carl June: The Cancer Slayer

The FDA just confirmed what we’ve known for years: Penn Medicine’s Carl June might be the most important doctor in the world.

Take a giant leap toward a cure for cancer, and everybody wants a piece of you. On an afternoon in late August, two days before the U.S. Food and Drug Administration approved his laboratory’s game-changing treatment for leukemia, Carl June was being patted with face makeup so he could look his best in a video being shot by the University of Pennsylvania, his employer. Nobody knew exactly when the FDA decision was coming, or whether it would be good news. But the video team had an hour of June’s time, and they wanted to get some footage ready. “Didn’t we say no lab coat?” the video director asked politely as June sat down in front of a window overlooking the Philly skyline. “I was just told ‘coat.’ But I don’t care,” the doctor said. “Are you okay with that?” “Sure,” June said, starting to remove the coat. Pause. “Do you usually wear your coat?” He took off the coat. Philly Magazine

WASHINGTON October 10th 2017:Dr. Carl June, Sens. Blunt and Casey to Receive AACI Awards

The 2017 AACI Distinguished Scientist Award will be presented to Carl H. June, MD, and U.S. Senators Roy Blunt (R-MO) and Bob Casey (D-PA) will receive the 2017 AACI Public Service Award at the Association of American Cancer Institutes’ annual meeting, October 15 – 17, in Washington, D.C.

Distinguished Scientist Award Presentation: Dr. June's talk will revolve around his ongoing work and recent FDA approval of gene transfer therapy to treat cancer. Clinical trials utilizing this approach, in which patients are treated with genetically engineered versions of their own T cells, are now underway for adults with chronic lymphocytic leukemia and adults and children with acute lymphoblastic leukemia. Trials of this approach have also begun for patients with other blood cancers and solid tumors including pancreatic cancer, mesothelioma, and the brain cancer glioblastoma. The implications of the first approval of gene transfer therapy by the US FDA will be discussed. Newswise Article AACI Meeting Program

PHILADELPIA August 30th 2017:FDA Approves Personalized Cellular Therapy for Advanced Leukemia Developed by University of Pennsylvania and Children’s Hospital of Philadelphia

Pioneering CAR T-cell Studies Led to First-ever Cancer Cell and Gene Therapy Approval

In a landmark decision for the field of cancer immunotherapy, the U.S. Food and Drug Administration (FDA) today approved a personalized cellular therapy developed by the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. The approval was granted to Novartis for the chimeric antigen receptor (CAR) T-cell therapy, Kymriah™ (tisagenlecleucel, formerly CTL019). In 2012, Penn and Novartis entered into a global collaboration to further research, develop and commercialize Kymriah and other CAR-T cell therapies for the treatment of cancers. Kymriah is the first therapy based on gene transfer approved by the FDA. PennMedicine Press Release Novartis Press Release

FDA Press Release Fierce Pharma NY Times Washington Post Fortune

PHILADELPHIA July 19th 2017:Human CAR-T Cell Glioblastoma Trial Generates Clues for Improving Treatment

Gene Engineering & Biotechnology News

Newswise article Penn Medicine Press Release


Science Translational Medicine Publication New York Times Perspective article interviewing Dr. Stephan Grupp A chimeric antigen receptor T-cell (CAR-T) therapy for glioblastoma (GBM) successfully crossed the blood–brain barrier to reach tumors in the brain, appeared safe, and reduced levels of its epidermal growth factor variant III (EGFRvIII) tumor target in GBM cells, in a first-in-man trial carried out by researchers at the University of Pennsylvania. The study also found that wide variation in EGFRvIII expression among patients, coupled with active immunosuppressive changes in the tumor in response to CAR T-cell infusion, may represent barriers to the clinical utility of the CAR-T therapy on its own. The autologous EGFRvIII-directed CAR-T therapy has been developed through an ongoing collaboration between researchers at the University of Pennsylvania and Novartis. The partnership has already resulted in the development of Novartis’ CAR-T therapy CTL019 (tisagenlecleucel), which just last week was unanimously recommended for approval by FDA’s Oncologics Drug Advisory Committee for treating relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) in children and young adults.

MARYLAND July 12th 2017:FDA Advisory Panel Votes 10-0 to Approve Tisagenlecleucel / CTL019

NY Times/Reuters

Washington Post Business Insider FiercePharma Novartis Press Release Novartis AG's pioneering cancer drug won the backing of a federal advisory panel on Wednesday, paving the way for the first gene therapy to be approved in the United States. An advisory panel to the Food and Drug Administration voted 10-0 that the drug, tisagenlecleucel, should be approved to treat patients with relapsed B-cell acute lymphoblastic leukemia (ALL), the most common form of U.S. childhood cancer. The FDA is not obliged to follow the recommendations of its advisers but typically does so. The agency is expected to rule on the drug by the end of September.

PHILADELPHIA July 11th 2017:First gene therapy — ‘a true living drug’ — on the cusp of FDA approvalw


An FDA advisory committee will decide Wednesday whether to recommend approval of the approach, which uses patients’ own genetically altered immune cells to fight blood cancers.

When doctors saw the report on Bill Ludwig’s bone-marrow biopsy, they thought it was a mistake and ordered the test repeated. But the results came back the same: His lethal leukemia had been wiped out by an experimental treatment never used in humans. “We were hoping for a little improvement,” remembers the 72-year-old retired New Jersey corrections officer, who had battled the disease for a decade. He and his oncologist both broke down when she delivered the good news in 2010. “Nobody was hoping for zero cancer.” The pioneering therapy with Ludwig and a few other adults at the University of Pennsylvania hospital paved the way for clinical trials with children. Six-year-old Emily Whitehead, who was near death, became the first pediatric recipient in 2012. Like Ludwig, she remains cancer-free. Such results are why the treatment is on track to become the first gene therapy approved by the Food and Drug Administration. An FDA advisory committee will decide Wednesday whether to recommend approval of the approach, which uses patients’ own genetically altered immune cells to fight blood cancers. If the panel gives the nod, the agency probably will follow suit by the end of September. That would open the latest chapter in immunotherapy — “a true living drug,” says Penn scientist Carl June, who led its development. FDA Briefing document (PDF)

PHILADELPHIA May 31th 2017: Personalized Cell Therapy Combined with Ibrutinib Achieves Complete Remission in High Percentage of Chronic Lymphocytic Leukemia Patients


Latest results from University of Pennsylvania trial investigating CAR Therapy to Treat CLL

Combining the kinase inhibitor ibrutinib with an investigational personalized cellular therapy known as CTL119 can lead to complete remission in patients with high-risk chronic lymphocytic leukemia (CLL), according to new research from the Perelman School of Medicine at the University of Pennsylvania and Penn’s Abramson Cancer Center (ACC). The team will present the results from its pilot study of this combination therapy during the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract # 193355). The team will present on the first 10 patients in the trial, each of whom had been taking ibrutinib for at least six months but had not achieved a complete remission. They were then infused with their own engineered “hunter” T cells. Eight of nine patients who are evaluable for response had no evidence of disease in their bone marrow at three months, and all remain in remission after a median follow-up period of six months, with a range from 0.5 to 9 months. One patient was found to have a partial response in their marrow. The research team is led by Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in the ACC, along with David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in the ACC. The data will be presented by the study’s first author, Saar Gill, MD, PhD, an assistant professor of Hematology-Oncology. Novartis Press Release Endpoints Article PharmaPhorum Article

WASHINGTON DC, May 13th 2017: PDCS Abstract Chosen for Clinical Trials Spotlight Symposium at American Society of Gene & Cell Therapy Meeting


TET2 Gene Disruption via Lentiviral Integration Promotes CAR T Cell Expansion and Persistence

“The immune system has a number of ways to fight leukemia, one of which is T cells. A common reason for failure of the immune system to eliminate tumor cells is that it does not recognize and kill “self” cancer cells. Though the T cells may still be fully functional, cancer cells are no longer recognized by the immune system as “unwanted”, causing cancer cells to win the arms race. It is now possible to use gene engineering to introduce molecules, such as chimeric antigen receptors, or “CARs” into T cells allowing them to target and attack a patient’s own cancer. In some cancers, however, war weary T cells even when endowed with new weapons for tumor mass destruction (CARS), cannot expand their numbers to mount a robust response. Researchers at the University of Pennsylvania recently uncovered the linchpin responsible for the elaboration of a strong and effective attack. With their approach, the T-cell genome is modified by integration of the CARs that direct tumor cell recognition and killing. During the genetic engineering process in one patient with chronic lymphocytic leukemia, the CAR landed in a genomic hotspot, disrupting a critical gene, Tet2. This event resulted in remodeling of DNA structure and allowed a single “super soldier” T cell to clone itself into a massive battalion that completely eradicated the patient’s cancer. Upon completion of its mission, the army of immune cells stood down, leaving a troop of sentinels behind in case the invader returns. Over 4-years later, the patient remains cancer-free. Thus, while battling cancer often relies on “strike hard and often” strategies, a careful tempering and appropriate deployment of specific immune cells is needed to win the war.” says J. Joseph Melenhorst, PhD, Director of the Product Development & Correlative Sciences laboratory and Adjunct Associate Professor of Pathology and Laboratory Medicine at the University of Pennsylvania and Joseph A. Fraietta, PhD, Associate Director of Product Development and Assistant Professor of Pathology and Laboratory Medicine at the University of Pennsylvania.

AJMC.com, January 2017: Cytokine Biomarkers Can Predict Response to CAR T-Cell Treatment in CLL

LINK At the 58th American Society of Hematology Annual Meeting & Exposition, held December 3-6, 2016, in San Diego, California, Jan Joseph Melenhorst, PhD, presented results of a study evaluating biomarkers of response to anti-CD19 CAR T-cell treatment in patients diagnosed with chronic lymphocytic leukemia (CLL). For this study, Melenhorst, adjunct associate professor of pathology and laboratory medicine, Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, collaborated with David L. Porter, MD, and Carl June, MD, who are pioneers in CAR T-cell research.


Fraietta JA, Lacey SF, Wilcox NS, et al. Biomarkers of response to anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with chronic lymphocytic leukemia. Presented at: the 58th American Society of Hematology Annual Meeting & Exposition; December 3, 2016; San Diego, CA. Abstract 57.

TIME MAGAZINE, December 2016: The CRISPR Pioneers


Person of the Year Runner-up

Dr. Carl June’s lab at the University of Pennsylvania looks like any other biology research hub. There are tidy rows of black-topped workbenches flanked by shelves bearing boxes of pipettes and test tubes. There’s ad hoc signage marking the different workstations. And there are postdocs buzzing around, calibrating scales, checking incubators and smearing solutions and samples onto small glass slides.

Appearances aside, what June is attempting to do here, on the eighth floor of the glass-encased Smilow Center for Translational Research in Philadelphia, is anything but ordinary. He’s built a career trying to improve the odds for people with intractable end-stage disease, and now, in the university’s brand-new cell-processing lab, he’s preparing to launch his most ambitious study yet: he’s going to try to treat 18 people with stubborn cancers, and he’s going to do it using CRISPR, the most controversial new tool in medicine.

SAN DIEGO, December 3rd to 6th 2016, 58th ASH Annual Meeting & Exposition: Strong Representation of Center for Cellular Immunotherapies Investigators at 2106 ASH Meeting

Twenty abstracts from Center for Cellular Immunotherapies investigators were accepted for presentation at the 58th American Society of Hematology (ASH) Annual Meeting & Exposition. Thirteen abstracts were accepted for oral presentation and seven abstracts for poster presentation. The majority of these abstracts featured PDCS authors and presented data generated by PDCS staff. The table below lists the numbers, titles and presenters of the abstracts. The full text and authors can be found at this link: Link to Abstracts Online The blog post at this link gives a feel for the intense interest in CAR-T therapies at this years's ASH meeting, and highlights some of the main messages.

PHILADELPHIA, Dec. 07, 2016: Tmunity Therapeutics Names Usman “Oz” Azam Chief Executive Officer

Press Release Endpoints News article

Tmunity Therapeutics, Inc. today announced that it has named Usman “Oz” Azam, M.D., to the new post of President and Chief Executive Officer. Dr. Azam will help to deliver the company’s vision to discover, develop, manufacture and market treatments that unleash the immunological potential of T cells to treat a wide variety of diseases. A veteran life sciences executive, Dr. Azam was most recently the Global Head of the Cell & Gene Therapies Unit at Novartis.

“With extensive U.S. and international pharmaceutical industry background, including key roles in science, clinical development, regulatory affairs and commercial activities, Oz brings the ideal skill set and breadth of perspective to Tmunity as we move our first T cell receptor and CAR programs toward the clinic,” said Carl H. June, M.D., co-founder and chief scientific advisor of Tmunity Therapeutics. “Oz shares our vision to make Tmunity the global leader in transforming the latest insights about T cell biology and T cell engineering into potentially curative therapies for patients.”

SAN DIEGO, Dec. 05, 2016: CAR T cell immunotherapy continues to yield complete responses in leukemia


A highly innovative, personalized cell-based treatment for a high-risk form of the most common childhood cancer continues to move through clinical trials. Pediatric oncologists from Children's Hospital of Philadelphia (CHOP) today reported new results using T cell immunotherapy against relapsed or refractory acute lymphoblastic leukemia (ALL).

The physician-scientists presented findings at the annual meeting of the American Society of Hematology today in San Diego. This immunotherapy modifies a patient's own immune T cells, extracted and engineered to potentially seek and destroy the patient's leukemia cells. The CHOP researchers reported on the first global, multicenter clinical trial of these cells and on a separate single-center trial, the first to use a version of these cells carrying a "humanized" protein more similar to human proteins. In both trials, the patients were children and young adults who had relapsed after previous leukemia therapies, and/or had persistent (refractory) disease. CHOP pediatric oncologist Stephan A. Grupp, MD, PhD, director of CHOP's Cancer Immunotherapy Frontier Program, co-moderated the ASH session on advances in immunotherapy for ALL at which these findings were presented. At this session, he reported results from the first global, multicenter trial of chimeric antigen receptor (CAR) T cells, of which he is the lead investigator. This study, sponsored by Novartis, is a global registration trial—one that will provide data to submit to the U.S. Food and Drug Administration (FDA), requesting approval for clinical use. It has enrolled 81 patients at 25 centers in the U.S., Canada, Europe, Japan and Australia. Among the 50 patients who have received a single dose of the T cells, designated CTL019 cells, 41 patients (82 percent) had a complete response (that is, no detectable leukemia cells) within one to three months after treatment.

PHILADELPHIA, November 26, 2016: New tricks in canine cancer research may improve treatments for humans, too

Washington Post Article

“Genetically, you are a lot more like your dog than that mouse running around a cage in the lab,” said Nicola Mason, a veterinarian and immunologist who oversees the vaccine and several other canine trials at Penn’s School of Veterinary Medicine. “Where dogs really stand out is in the way they generate tumors and react to treatments, which is a lot like people.”

Most cancer drugs for dogs were developed first for humans. Take Harley, a striking 4-year-old black boxer with aggressive leukemia. He recently came to Penn for a treatment called CAR T-cell therapy, which has shown some promising results in trials for people with blood cancers. The immunotherapy procedure for dogs is similar to the human one: T cells, a key component of the immune system, are extracted, genetically modified in the lab to bolster their cancer-killing abilities, increased in number and then reinfused. Mason began working on the treatment for dogs when she was a postdoctoral fellow in the lab of Carl June, a prominent researcher at Penn’s Perelman School of Medicine and a CAR T-cell pioneer. She consults with him frequently. Owners of dogs in the Penn Vet trials get much of the care free, including treatments and follow-up visits. But there can be related expenses. In the osteosarcoma trial, owners are required to pay for the amputation and chemo.

PHILADELPHIA, November 17, 2016: Genetically Engineered T Cells Render HIV's Harpoon Powerless

Penn Medicine Press Release

Penn Team to Test "Broader, More Potent" Peptide Approach in HIV Patients

When HIV attacks a T cell, it attaches itself to the cell’s surface and launches a “harpoon” to create an opening to enter and infect the cells. To stop the invasion, researchers from the Penn Center for AIDS Research at the University of Pennsylvania and scientists from Sangamo BioSciences, Inc. have developed genetically engineered T cells armed with a so-called “fusion inhibitor” to disrupt this critical step and prevent a wide range of HIV viruses from entering and infecting the T cells. The findings were reported today online in a preclinical study in PLOS Pathogens.

HIV medicine experienced a breakthrough in the early 2000s with a unique class of drugs known as “fusion inhibitors.” Unlike most drugs that block virus replication inside of T cells, these drugs prevent HIV from entering cells in the first place. The drug, enfuvirtide, modeled after a peptide from the viral envelope and used today in combination with other antiretroviral therapies, has been shown to keep the virus at bay. However, patients need to inject enfuvirtide daily under their skin, limiting its utility and acceptability to patients, especially when compared to many other orally available drugs. HIV can also become resistant to enfuvirtide.

Building on this approach with a powerful genetic technique, researchers developed a novel way to deliver the fusion inhibitor peptide precisely to the spot on the cell surface where the virus attaches and launches its envelope, like a harpoon. The team genetically altered T cells by introducing a so-called C34 peptide, modeled after enfuvirtide, directly onto receptors, CXCR4 and CCR5, which are crucial for HIV entry. By using these molecules to deliver the C34 peptide to the site where the virus enters, these investigators showed that HIV was potently inhibited and that this inhibition extended to genetically diverse HIVs, including those that were resistant to the drug, enfuvirtide.

The most impressive results were seen when the C34 peptide was attached to CXCR4, where the Penn investigators showed that T cells expressing this molecule were protected in a mouse model of HIV infection.

“We believe that our approach to precisely target an inhibitory drug to the site of viral entry creates a new way to engineer human T cells to become resistant to HIV infection,” said senior author James Hoxie, MD, a professor of Medicine in the division of Hematology/Oncology in the Perelman School of Medicine at the University of Pennsylvania. “It’s potent and very broad. Every strain of HIV we tried was sensitive to it, regardless of whether the virus used CCR5 or CXCR4, which is a big advantage, since HIV typically uses CCR5 to establish infection, but can over time, evolve to use a CXCR4 instead. With this approach, it doesn’t matter where the virus came from or what cellular molecule it needs to infect cells.”

The findings set the stage for an upcoming phase I clinical trial in HIV-positive patients to determine the safety and appropriate dosage of a patient’s own T cells engineered to express the C34-CXCR4 molecule, as well as to demonstrate their ability to resist infection when antiretroviral therapy is interrupted. The clinical trial investigating the work with C34 is slated to start in December 2016. The researchers will infuse C34-CXCR4 expressing T cells into well-controlled HIV-infected individuals. It will be a dose-escalation study in which 1, 3, or 10 billion engineered T cells will be infused. After infusion, an “analytical treatment interruption” will occur for about 16 weeks and time to viral rebound and enrichment for the C34-CXCR4 expressing cells will be monitored. At present, patients infected with HIV must continue to take anti-HIV drugs to prevent the virus from replicating and causing disease. Efforts are underway at Penn and throughout the world to develop strategies that will enable drug therapy for HIV to be discontinued safely.

PHILADELPHIA, PA, October 25, 2016: Tech giant Sean Parker launches Penn's cancer immunotherapy center


Billionaire tech guru Sean Parker told an audience at the University of Pennsylvania on Tuesday that he wants to bring hacker culture to the field of immunotherapy.

But he wasn’t talking about computer geeks waging malicious cyberattacks. “The term hacker has a different connotation for me,” said Parker, a self-described “hacker-philanthropist.” “It has to do with finding creative, novel solutions to problems.” Parker’s remarks were part of a panel presentation celebrating the official launch of Penn’s participation in the Sean Parker Institute for Cancer Immunotherapy. The panel, featuring top Penn scientists and leaders, was moderated by pediatrician Richard Besser, who is ABC News’ chief medical editor (and a Penn Medical School graduate).

Parker’s new institute -- announced in April, along with $250 million in funding from his foundation -- aims to accelerate the development of revolutionary cancer therapies by uniting Penn with five other leading research centers: Memorial Sloan-Kettering Cancer Center; Stanford Medicine; the University of California, Los Angeles; the University of California, San Francisco; and the University of Texas MD Anderson Cancer Center. The institute links more than 300 researchers, all devoted to immunotherapy — harnessing the immune system to fight cancer.

WASHINGTON, DC, June 21, 2016: First proposed human test of CRISPR passes initial safety review

Science News Article Fierce Biotech Article Stat News Article

A cancer study that would represent the first use of the red-hot gene-editing tool CRISPR in people passed a key safety review today. The proposed clinical trial, in which researchers would use CRISPR to engineer immune cells to fight cancer, won approval from the Recombinant DNA Advisory Committee (RAC) at the U.S. National Institutes of Health, a panel that has traditionally vetted the safety and ethics of gene therapy trials funded by the U.S. government and others.

Although other forms of gene editing have already been used to treat disease in people, the CRISPR trial would break new ground by modifying three different sites in the genome at once, which has not been easy to do until now. The study has also grabbed attention because—as first reported by the MIT Technology Review—tech entrepreneur Sean Parker’s new $250 million Parker Institute for Cancer Immunotherapy will fund the trial.

The proposed CRISPR trial builds off the pioneering efforts of Carl June and others at University of Pennsylvania (UPenn) to genetically modify a cancer patient’s own immune cells, specifically a class known as T cells, to treat leukemia and other cancers. For the CRISPR trial, a UPenn-led team wants to remove T cells from patients and use a harmless virus to give the cells a receptor for NY-ESO-1, a protein that is often present on certain tumors but not on most healthy cells. The modified T cells are then reinfused back into a patient and, if all goes well, attack the person’s NY-ESO-1–displaying tumors. The UPenn team has already tested this strategy in a small clinical trial for multiple myeloma. But although most patients’ tumors initially shrank, the reintroduced T cells eventually became less effective and stopped proliferating.

To boost the staying power of the engineered T cells, the UPenn group wants to use CRISPR to disrupt the gene for a protein called PD-1. The protein sits on the surface of T cells and helps dampen the activity of the cells after an immune response, but tumors have found ways to hide from T cell attack by flipping on the PD-1 switch themselves. (Drugs that block PD-1 eliminate this immune suppression and have proven to be a promising immunotherapy cancer treatment.) June’s team also wants to knock out two gene segments that encode different portions of the protein that makes up a T cell’s primary receptor so that the engineered NS-ESO-1 receptor will be more effective. To do this, they will introduce into the T cells so-called guide RNAs, which tell CRISPR’s DNA-snipping enzyme, Cas9, where to cut the genome. The 2-year trial will treat 18 people with myeloma, sarcoma, or melanoma who have stopped responding to existing treatments at three sites that are members of the Parker Institute—UPenn; the University of California, San Francisco; and the University of Texas MD Anderson Cancer Center in Houston.

LOS ANGELES, April 13, 2016: University of Pennsylvania to Join First-of-its-Kind Research Collaboration to Fight Cancer with New Immunotherapies

Penn Medicine Press Release Washington Post Article Wired Article NY Times Article WSJ Article

$250 Million Grant to Launch Parker Institute for Cancer Immunotherapy Poised to Accelerate New Discoveries and Treatments

The University of Pennsylvania has joined an unprecedented cancer research effort, the Parker Institute for Cancer Immunotherapy, which unites six of the nation’s top medical schools and cancer centers around a shared aim of accelerating breakthrough immunotherapy research that will turn more cancers into a curable disease. The venture is backed by a $250 million gift from the Parker Foundation, making it the largest single contribution ever made to the field of immunotherapy. The Parker Foundation was founded by Sean Parker in June 2015 with a $600 million gift to spur innovations in the life sciences, global public health, and civic engagement. “We are tremendously excited to join this collaboration, which will allow us to investigate promising new immunotherapy avenues for the treatment of cancer outside of our institutional silos in very unique ways,” said the Parker Institute’s Penn director, Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of Translational Research in the Abramson Cancer Center.“Working together will enable us to make quicker progress as we work to translate our laboratory findings into clinical trials.” Initial funding of $10 to 15 million has been awarded to set up the Parker Institute at Penn. This investment will continue to grow on an annual basis via additional project grants, shared resources and central funding.The funding will support laboratory studies and clinical trials, recruitment of talented new faculty, and support for early-career investigators who will train at Penn. The effort will augment Penn’s longstanding commitment to cancer research. In 2015, more than 10,000 patients participated in Abramson Cancer Center clinical trials. Nearly 1,100 trials are currently underway, 80 of which are immunotherapy studies.

PHILADELPHIA, Jan. 12, 2016: Tmunity Therapeutics, Inc. to Advance IND-Enabling Activities for Personalized Next-Generation Engineered T Cell Therapies with $10 Million Financing

Press Release

Tmunity Therapeutics today announced that it is raising $10 Million in equity financing from Penn Medicine, the academic medical center of the University of Pennsylvania (Penn), and Lilly Asia Ventures, a premier venture capital firm focused on making investments in the life sciences sector.

The financing will represent the first capital investment for Penn Medicine in a company co-founded by Penn faculty and researchers. The proceeds of the financing will be used to develop novel products to unleash the immunological potential of T cells to treat a wide range of diseases. Tmunity is developing novel T Cell Receptor (TCR) engineered T cells, regulatory T cells (Treg), and universal engineered T cell platforms that exhibit best-in-class control over T cell activation and direction in vivo. The company is also developing proprietary technologies to activate, expand, and genetically engineer T cells from peripheral blood, cord blood and tumors. These will rapidly advance toward the clinic personalized next-generation engineered T cell immunotherapies for cancer, infectious diseases and autoimmune disease. Philadelphia Business Journal article

January 15th 2016: Vice President of the United States Joe Biden visits the Abramson Cancer Center

The VPOTUS held discussions with physicians and researchers, including Center for Cellular Immunotherapy staff Carl June, Robert Vonderheide, Bruce Levine, and Stephan Grupp, and toured the Center for Advanced Cellular Therapy. This made the University of Pennsylvania cancer center the formal launching pad for the Obama administration’s cancer “moonshot" following President Obama's State of The Union address on 1/12/2016.

CBS News story USA Today coverage Philly.com STAT perspective article

September 9th 2015: Penn Researchers Report Sustained Remission After Treatment with Investigational Personalized Cellular Therapy In Patient with Multiple Myeloma

New Treatment Combination with CTL019 Targets Precursors of Cancerous White Blood Cells

LINK PHILADELPHIA New Treatment Combination with CTL019 Targets Precursors of Cancerous White Blood Cells – A multiple myeloma patient whose cancer had stopped responding after nine different treatment regimens experienced a complete remission after receiving an investigational personalized cellular therapy known as CTL019 developed by a team at the University of Pennsylvania. The investigational treatment was combined with chemotherapy and an autologous stem cell transplant – a new strategy designed to target and kill the cells that give rise to myeloma cells. The team’s findings are published in a case report today in the New England Journal of Medicine. Prior to receiving the therapy, the patient had already received nine different therapy regimens in the five years since her diagnosis, including a previous autologous stem cell transplant, which had only controlled her disease for a few months. Her bone marrow was almost entirely filled by cancerous cells when she entered the study. By 130 days after receiving the infusion of engineered cells, tests revealed no evidence of disease. The patient – who was the first to be treated as part of this trial – remains in remission more than 12 months after receiving this therapy.

September 2nd 2015: Abramson Cancer Center Researchers Report Long-Term Remissions in First Group of Patients to Receive Personalized Cellular Therapy for Chronic Lymphocytic Leukemia

‘Penn Study Details Emerging Field's Most Mature Findings'

LINK PHILADELPHIA – Eight of 14 patients in the first trial of the University of Pennsylvania’s personalized cellular therapy for chronic lymphocytic leukemia (CLL) responded to the therapy, with some complete remissions continuing past four and a half years. These results, published today in Science Translational Medicine, represent the most mature data from clinical trials of an approach known as CTL019, developed by a team from Penn’s Abramson Cancer Center and the Perelman School of Medicine. In 2011, the research team published initial findings from the first three patients to enroll in the trial. Two of those patients had complete responses, and their leukemia remains in remission today, more than four and a half years after receiving the therapy. The first patient to receive the therapy recently marked five years cancer-free. “The durability of the remissions we have observed in this study are remarkable and have given us great hope that personalized cell therapies are going to be important options for patients whose cancers are no longer treatable with standard approaches,” said lead author David L. Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in Penn’s Abramson Cancer Center. “The patients in this study are pioneers, whose participation has given us a foundation of knowledge and experience on which to build this new approach to help more patients.” The new study details the completed, 14-patient pilot trial of CTL019 for CLL, which began in the summer of 2010. The overall response rate was 57 percent. All patients who received the experimental therapy, which is made from their own immune cells, had cancer that had relapsed or continued to progress after receiving multiple conventional Food and Drug Administration-approved therapies, and few were eligible for bone marrow transplants.

Related news articles:

Fierce biotech NBC News Science Translational Medicine

July 20th 2015: Investigational T-cell Receptor Therapy Achieves Encouraging Clinical Responses in Multiple Myeloma Patients, Penn-led Study Finds

‘NY-ESO T cell receptor therapy found to be safe, with no cytokine release syndrome cases; engineered cells persisted in most patients for up to two years after infusion'

LINK PHILADELPHIA – Results from a clinical trial investigating a new T cell receptor (TCR) therapy that uses a person’s own immune system to recognize and destroy cancer cells demonstrated a clinical response in 80 percent of multiple myeloma patients with advanced disease after undergoing autologous stem cell transplants (ASCT). This time, researchers modified T cells to attack cancer cells expressing NY-ESO-1, an antigen found in nearly 60 percent of multiple myelomas and previously shown to be associated with tumor growth and poor prognosis. The results of the study were published this week in the journal Nature Medicine from researchers at Penn’s Abramson Cancer Center, including senior author Carl H. June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in the ACC, the University of Maryland School of Medicine, and Adaptimmune Therapeutics plc (Adaptimmune). In the phase I/II clinical trial of 20 patients, the engineered cells were deemed safe, trafficked to the site of the tumor (bone marrow), and persisted in 90 percent of the patients who reached two years follow up after infusion, the research team found. Significant anti-tumor activity was observed as well: nearly 70 percent had a near complete or complete response within three months post treatment, which compares favorably with the expected responses (less than 40 percent) in patients without high-risk disease following an ASCT.

This is the first published report of lentiviral vector mediated TCR therapy that has shown persistence beyond one month, June said. “This study shows us that these TCR specific T cells are safe and feasible in patients expressing NY-ESO-1,” he said. “But it also revealed encouraging anti-tumor activity and showed impressive durable T cell persistence.”

Penn co-authors include Bruce L. Levine, Don L. Siegel, Naseem Kerr, Minnal Gupta, Irina Kulikovskaya, Jeffrey Kinklestein, Brendan Weiss, Alfred Garfall, Simon F. Lacey, and Dan T. Vogl.

June 17th 2015: CTL019 Shows Early Promise in Multiple Myeloma

CTL019, a breakthrough CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, demonstrated intriguing antitumor activity in a small study of patients with refractory multiple myeloma, including those with heavily pretreated disease, according to data presented at the 2015 ASCO Annual Meeting and again at the 20th EHA Congress.

LINK LINK In the small 5-patient study, all but 1 patient responded to treatment with CTL019, which included 1 stringent complete response (sCR) with MRD-negativity at a 339-day follow-up. Other responses included a partial response (PR) and a very good PR (VGPR). One patient experienced an unconfirmed CR with MRD-positivity; however, this patient progressed after 6 months. "These early results suggest that CTL019 and autologous transplant in patients with myeloma is safe and feasible," lead author Alfred L. Garfall, MD, from the Abramson Cancer Center at the University of Pennsylvania, said during his presentation. "We saw evidence of clinical benefit in 3 of 4 patients with greater than 100 days of follow-up."

American Society of Clinical Oncology Annual Meeting Abstract 8517 [oral presentation]: Garfall AL, Maus MV, Lacey SF, et al. Safety and efficacy of anti-CD19 chimeric antigen receptor (CAR)-modified autologous T cells (CTL019) in advanced multiple myeloma. J Clin Oncol. 2015;33 (suppl; abstr 8517)

June 2nd 2015: Novartis CTL019 CAR T cell therapy demonstrates potential to treat B-cell lymphomas

Novartis is highlighting data from an ongoing Phase II clinical study of CTL019, an investigational chimeric antigen receptor (CAR) T cell therapy, that indicate its potential in the treatment of specific types of hard-to-treat non-Hodgkin lymphoma.

LINK Findings from the ongoing study conducted by the University of Pennsylvania's Perelman School of Medicine (Penn) in adults with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) found an overall response rate (ORR) of 100% in patients with FL and 50% in patients with DLBCL. Thirteen of 19 evaluable patients responded to the therapy. Eleven achieved a complete response (CR) and two experienced a partial response (PR) to treatment. These results will be presented in an oral session at the 51st American Society of Clinical Oncology (ASCO) Annual Meeting on Monday, June 1 J Clin Oncol. 2015;33 (suppl; abstr 8516)

"The results from this ongoing study of CTL019 are encouraging, as we now have data through six months showing that patients may have achieved durable overall response rates," said lead investigator Stephen Schuster, M.D., associate professor, division of Hematology/Oncology at the University of Pennsylvania, Abramson Cancer Center. "These data support our ongoing efforts to determine the potential role of CTL019 in improving outcomes for patients with certain types of B-cell lymphomas."

April 1st 2015:

LINK Episode Three: Finding the Achilles Heel (Wednesday, April 1, 2015/9-11PM ET) This episode picks up the story at another moment of buoyant optimism in the cancer world: Scientists believe they have cracked the essential mystery of the malignant cell and the first targeted therapies have been developed, with the promise of many more to follow. But very quickly cancer reveals new layers of complexity and a formidable array of unforeseen defenses. In the disappointment that follows, many call for a new focus on prevention and early detection as the most promising fronts in the war on cancer. But other scientists are undeterred, and by the second decade of the 2000s their work pays off. The bewildering complexity of the cancer cell, so recently considered unassailable, yields to a more ordered picture, revealing new vulnerabilities and avenues of attack. Perhaps most exciting of all is the prospect of harnessing the human immune system to defeat cancer. This episode includes patients Doug Rogers, a 60-year-old NASCAR mechanic with melanoma, and Emily Whitehead, a six-year-old child afflicted with leukemia. Each is a pioneer in new immunotherapy treatments, which the documentary follows as their stories unfold. Both see their advanced cancers recede and are able to resume normal lives.

March 2015: VICE Special Report: 'Killing Cancer'

‘My life, like most people's, has been negatively affected by cancer, and the thought of my young children living in an age where this is no longer humanity's No. 1 health fear was simply overpowering. - Shane Smith'

LINK Cancer has been such a scourge of humanity for so long that the very word inspires a deep dread in anyone who hears it—it's a two-syllable gut punch, a hole that suddenly opens up beneath you. Similarly, a "cure for cancer" has been a holy grail of modern medical research the way getting to the moon used to inspire space programs. All told, the world has spent decades and billions of dollars trying to cure cancer, or cure some kinds of it, or simply make some of them less awful and deadly—and VICE is going to give viewers an inside look at the most cutting-edge cancer treatments in the world. The third season of our Emmy-winning HBO show doesn't start until March 6, but you can watch VICE Special Report: Killing Cancer online now. It's an hour-long in-depth documentary that focuses on therapies that go far, far beyond chemo. We'll be taking a look at how doctors use HIV, measles, and genetically-engineered cold viruses to strengthen patients' immune systems and wipe out cancer cells without damaging their bodies the way chemo normally does.

February 18th 2015: Penn Medicine Study Describes Development of Personalized Cellular Therapy for Brain Cancer

‘Preclinical Study Results Pave the Way for Newly Opened Clinical Trial of Immune Cells Engineered to Attack Protein Found on Tumors in 30 Percent of Patients with Glioblastoma '

LINK PHILADELPHIA — Immune cells engineered to seek out and attack a type of deadly brain cancer were found to be both safe and effective at controlling tumor growth in mice that were treated with these modified cells, according to a study published in Science Translational Medicine by a team from the Perelman School of Medicine at the University of Pennsylvania and the Novartis Institutes for BioMedical Research. The results paved the way for a newly opened clinical trial for glioblastoma patients at Penn.

December 2014: Watch A Man Tell How Killer T-Cells Eradicated His Cancer

‘There's probably not a hotter area of biotechnology right now than what's known as CART therapy, in which a patient's own white blood cells are genetically engineered to attack cancer.'

LINK Matthew Herper, staff writer, FORBES– All this excitement is over a complicated and some might say cumbersome therapy. CART stands for chimeric antigen receptor T-cell; these immune cells are removed from the patient’s body, and a genetically engineered receptor is added that teaches the cells to kill cancer cells. Then the cells are infused back in, often causing severe and sometimes deadly side effects as the body’s immune system goes into overdrive. Right now, the positive results are all from CARTs that are designed to kill B cells expressing CD19, which are the cells that go wrong in many types of cancer. Patients can live without B cells, but to take on other cancers, the CARTs are going to need to stop killing at some point, or kill only cancer cells. But none of that gets across the reason that there’s so much excitement. What does? Well the video I’ve put in this post. This is a patient named Douglas Olson, a long-time healthcare industry consultant. I met him while reporting a cover story on CART therapy earlier this year. Doug was the second patient to receive CART cells at the University of Pennsylvania; this was the program later licensed by Novartis. He’s now been cancer-free and healthy for four years. (The eyepatch is temporary, due to a detached retina, and is not related to the CART treatment.) Want to understand why people are crazy excited about this new treatment? Listen to Doug. The video is taken from the third annual Forbes Healthcare Summit, which was held on Dec. 8 and Dec. 9, 2014.

December 2014: American Society of Hematology (ASH) Annual Meeting News

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‘Penn Medicine Researchers Announce Latest Results of Investigational Cellular Therapy CTL019 '

LINK SAN FRANCISCO – The latest results of clinical trials of more than 125 patients testing an investigational personalized cellular therapy known as CTL019 will be presented by a University of Pennsylvania research team at the 56th American Society of Hematology Annual Meeting and Exposition. Highlights of the new trial results will include a response rate of more than 90 percent among pediatric acute lymphoblastic leukemia patients, and results from the first lymphoma trials testing the approach, including a 100 percent response rate among follicular lymphoma patients and 45 percent response rate among those with diffuse large B-cell lymphoma.

Related news Articles:

Fierce BiotechNovartis Press Release

October 16th 2014 Personalized Cellular Therapy Achieves Complete Remission in 90 Percent of Acute Lymphoblastic Leukemia Patients Studied

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‘University of Pennsylvania and Children's Hospital of Philadelphia Studies Reveal Unprecedented Results with Investigational Therapy Made From Patients' Own Immune Cells'

LINK PHILADELPHIA — Ninety percent of children and adults with acute lymphoblastic leukemia (ALL) who had relapsed multiple times or failed to respond to standard therapies went into remission after receiving an investigational personalized cellular therapy, CTL019, developed at the Perelman School of Medicine at the University of Pennsylvania. The results are published this week in The New England Journal of Medicine. The new data, which builds on preliminary findings presented at the American Society of Hematology’s annual meeting in December 2013, include results from the first 25 children and young adults (ages 5 to 22) treated at the Children’s Hospital of Philadelphia and first five adults (ages 26 to 60) treated at the Hospital of the University of Pennsylvania. Twenty-seven of the 30 patients in the studies achieved a complete remission after receiving an infusion of these engineered “hunter” cells, and 78 percent of the patients were alive six months after treatment.

Related news Articles:

New York Times Fierce Biotech

Newsweek Philadelphia Business Journal

September 11th 2014 Center for Advanced Cellular Therapeutics to Rise on Penn Medicine Campus:

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‘New Facility Poised to Accelerate the Research and Development of Personalized Cellular Cancer Therapies'

LINK PHILADELPHIA — A University of The University of Pennsylvania today reached an important milestone in its alliance with Novartis as it unveiled plans for the construction of a first-of-its-kind Center for Advanced Cellular Therapeutics (CACT) on the Penn Medicine campus in Philadelphia. The CACT will become the epicenter for research using Chimeric Antigen Receptor technology (CAR), which enables a patient’s T cells to be reprogrammed outside of the body so when they are re-infused into the patient, the T cells have the ability to “hunt” and destroy the cancer cells. Clinical trials using this approach have made headlines around the world.

Plans for the 30,000-square foot facility cement the Penn-Novartis alliance, a marquee component of Penn's efforts in translational sciences that expedite the development of novel therapies for diseases of all kinds. The collaboration was announced in August 2012, when the two organizations entered an exclusive global research and licensing agreement to further study and commercialize novel CAR therapies.

The CACT, which will be funded in part through a $20 million investment from Novartis, will be devoted to the discovery, development and manufacturing of these personalized cellular cancer therapies, through a joint research and development program led by scientists and clinicians from Penn and Novartis.

July 10th 2014 Marco Ruella Receives 2014 SITC-EMD Serono Cancer Immunotherapy Clinical Fellowship Award:

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‘Dual Chimeric Antigen Receptor T Cell Therapy for Human B-Cell Acute Lymphoblastic Leukemia.'

LINK The Society for Immunotherapy of Cancer (SITC) is pleased to announce that SITC member, Marco Ruella, MD of the University of Pennsylvania, is the recipient of the 2014 SITC-EMD Serono Cancer Immunotherapy Clinical Fellowship Award. This award is the first of its kind offered by the Society. Congratulations Dr. Ruella! Dr. Ruella was selected as the winner of this award for his project, titled, “Dual Chimeric Antigen Receptor T Cell Therapy for Human B-Cell Acute Lymphoblastic Leukemia.”

“I’m very honored to be the first recipient of this fellowship award and I would like to thank the Society and the award committee for choosing my project,” said Dr. Ruella. “The goal of my research project is to treat patients with relapsing or refractory B-cell Leukemia with Chimeric Antigen Receptor T cells targeting multiple antigens, in order to avoid tumor escape. As powerful new therapies are developed that enhance the immune response to malignancy, it will be important for us to stay ahead of cancer’s escape mechanisms. One way to do this is with combination therapies.”

This year’s award was established through the generosity of EMD-Serono and is intended to support the development of the next generation of immunotherapy experts. Through this funding of novel research, the Society intends to cultivate those individuals who have a vested interest in furthering the clinical research and translation of cancer immunotherapy.

July 7th 2014 University of Pennsylvania's Personalized Cellular Therapy for Leukemia Receives FDA's Breakthrough Therapy Designation:

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‘Engineered Cells Known As CTL019 Are the First Therapy of Their Kind to Obtain Designation'

LINK PHILADELPHIA — A University of Pennsylvania-developed personalized immunotherapy has been awarded the U.S. Food and Drug Administration’s Breakthrough Therapy designation for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia (ALL). The investigational therapy, known as CTL019, is the first personalized cellular therapy for the treatment of cancer to receive this important classification.

In early-stage clinical trials at the Hospital of the University of Pennsylvania and the Children’s Hospital of Philadelphia, 89 percent of ALL patients who were not responding to conventional therapies went into complete remission after receiving CTL019. “Our early findings reveal tremendous promise for a desperate group of patients, many of whom have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,” said the Penn research team’s leader, Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of Translational Research in the Abramson Cancer Center of the University of Pennsylvania. “Receiving the FDA’s Breakthrough Designation is an essential step in our work with Novartis to expand this therapy to patients across the world who desperately need new options to help them fight this disease.” The FDA’s Breakthrough Therapy designation, created in 2012, is intended to expedite the development and review of new medicines – both drugs and biologic agents – that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over available therapies. The FDA has previously granted Breakthrough Therapy to only four other biologic agents.

June 2014 Taubman Prize:

‘Leukemia researcher Carl June, M.D. awarded 2014 Taubman Prize'

LINK ANN ARBOR, Mich. — A physician-scientist who developed a personalized immunotherapy for leukemia using patients’ own T cells is the recipient of the 2014 Taubman Prize for Excellence in Translational Medical Science, awarded by the A. Alfred Taubman Medical Research Institute at the University of Michigan Medical School. Carl June, M.D. of the Perelman School of Medicine at the University of Pennsylvania will receive the $100,000 prize in recognition of the treatment he designed that is credited as the first successful and sustained demonstration of the use of gene transfer therapy to turn the body’s own immune cells into weapons aimed at cancerous tumors.

May 26th 2014 Forbes:pbs logo

‘Is This How We'll Cure Cancer?'

LINK Emily Whitehead has become the poster child for a radical new treatment that Novartis, the third-biggest drug company on the Forbes Global 2000, is making one of the top priorities in its $9.9 billion research and development budget.

April 1st 2014 The Scientist:pbs logo

‘Commander of an Immune Flotilla'

LINK With much of his early career dictated by US Navy interests, Carl June drew inspiration from malaria, bone marrow transplantation, and HIV in his roundabout path to a breakthrough in cancer immunotherapy.

March 6th, 2014 The Inquirer:pbs logo

‘Penn researchers 'edit' genes to make cells resist HIV

LINK University of Pennsylvania researchers have snipped out a single gene in patients' immune cells to make them partly resistant to infection with HIV, the virus that causes AIDS. The study, in this week's New England Journal of Medicine, bolsters hope for controlling HIV without daily antiviral drugs - a so-called functional cure.

March 6, 2014 Penn Medicine News Release: ash logo

Personalized Gene Therapy Locks Out HIV, Paving the Way to Control Virus Without Antiretroviral Drugs - Penn Researchers Used Zinc Finger Technology to Safely Build Up Army of Modified T Cells to Repel Virus

LINK PHILADELPHIA — University of Pennsylvania researchers have successfully genetically engineered the immune cells of 12 HIV positive patients to resist infection, and decreased the viral loads of some patients taken off antiretroviral drug therapy (ADT) entirely—including one patient whose levels became undetectable. The study, appearing today in the New England Journal of Medicine, is the first published report of any gene editing approach in humans.

February 2014 Fierce Biotech:

The most influential people in biopharma today: Carl June - University of Pennsylvania

LINK The University of Pennsylvania's Carl June is arguably one of the most well-known researchers in the cancer field right now--and for good reason. June is the director of translational research and a professor of pathology and laboratory medicine in Penn's Abramson Cancer Center and Perelman School of Medicine, and he's designed customized T cells to help give a patient's own immune system the lasting ability to fight cancer.