efforts in the Translational and Correlative Studies Laboratory focus on 2
1. The development of comprehensive and quality-driven platforms and assays to evaluate, through hypothesis testing and hypothesis generating studies, the impact of immune-based experimental treatments on patient biology and the tumor, to allow for a rational and data driven iterative cycle of clinical research and biomarker discovery.
Clinical trials where the TCSL is involved include clinical trials of adoptive T cell therapies for leukemias, lymphomas, myeloma, melanoma and other malignancies. Several of these clinical studies involve the genetic engineering of patient T-cells to express chimeric antigen receptors (CARs) specific for target antigens such as CD19. The TCSL analyzes patient biological samples to evaluate the presence, long term persistence, and functionality of the infused cells as well as the patient immunological status and the tumor, using state of the art immunological and molecular techniques including polychromatic flow cytometry, multiplex Luminex assays to measure soluble factors in serum, plasma, cerebrospinal fluid and other biological samples, qPCR to quantify levels of gene-modified T cells, qRT-PCR and Quantigene multiplex assays to examine gene expression, deep sequencing to evaluate diversity of T cell repertoire, and protein arrays to examine antibody repertoires. The objectives of these studies include the identification of biomarkers that track the effectiveness of the therapeutic interventions and can be used to predict clinical outcomes. This information can guide patient management, as well as support the development of improved adoptive cell therapies.
2. Translational research studies focused on the development of novel adoptive T cell-based approaches to enhance patient immunity against cancer to mediate effective anti-tumor immunity. Novel CAR constructs recognizing various tumor antigens are designed and evaluated in cell culture systems and model systems of cancer to enable and facilitate the development of clinical protocols.