T-cell receptor gene therapy of cancer
Discovery of a cancer specific T-cell receptor library for gene therapy of cancer
Potent and safe T-cell receptors (TCRs) specific for cancer antigens and useful for T-cell-receptor gene therapy of cancer patients will be identified by the LUMC in this project. The industrial partner Bellicum Pharmaceuticals will initiate clinical studies in which cancer patients will be treated with these tumour-specific TCRs in combination with their recently developed inducible suicide switch (link).
Gene therapy makes it possible to engineer tumour-specific T-cells by chimeric antigen receptors (CARs) or TCRs, and those engineered T-cells have demonstrated powerful anti-tumour reactivity in cancer therapy. TCRs have the conceptual advantage that both antigens derived from extracellular and intracellular proteins can be recognised in the context of human leukocyte antigen (HLA) molecules at the cell surface of target cells.
Recently, we have developed a high-throughput strategy to identify high-affinity, tumour-specific TCRs. With this strategy we identified such TCRs: 1) TCRs specific for PRAME, recognising a high variety of cancers, and 2) TCRs specific for the B-cell transcription factor BOB1, which exert highly potent reactivity against different B-cell malignancies, including multiple myeloma. Bellicum Pharmaceuticals will now initiate clinical studies with these different tumour-specific TCRs.
In this project, we will explore whether more high-affinity TCRs directed against other tumour-associated antigens can be identified so as to increase the number of cancer patients who can be treated with TCR gene therapy. With the TCR gene therapy studies we hope to develop effective medicines for cancer patients that will either lead to a cure or prevent cancer progression and therefore improve these patients' quality of life.
Pictuer: Courtesy of C.P. Ho