Immunotherapy: CAR T and TCR applications
CAR T and TCR oncology applications employ genetically modified T cells expressing chimeric antigen receptors (CARs) or engineered T-cell receptors (TCRs). This cellular immunotherapy, also known as adoptive cell therapy, targets specific antigens on the tumor cell surface. CAR-T cell therapy has shown efficacy for hematological malignancies of the B-cell lineages – in 2017 the FDA approved the first CAR-T cell therapy for large B-cell lymphoma. CAR-T cell therapies are showing promise against solid tumors, whereas TCR-engineered T-cell therapy has produced some positive results in treating solid tumors.
TCRs rely on the interaction with peptide-major histocompatibility complex (pMHC) to produce a therapeutic response, and CARs do not – they utilize a single-chain fragment variant (scFv) which recognizes specific antigens on the tumor cell surface.
Another approach is harnessing stem cells to create a supply of CAR-T cells, which could fast-track treatment for patients. Both types of immunotherapy are being extensively researched. This includes exploring new targets such as BCMA, CD123, CD33 (for CAR-T cells) and WT-1, L1CAM, HPV-16 (for TCR T-cells). Human xenograft models representative of both solid and hematological malignacies are extensively utilized in the preclinical development, and our preclinical oncology team has run more than 450 cell therapy based studies between 2015 and 2020.