T-cell receptor 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 tumor specific TCRs in combination with their recently developed inducible suicide switch.

Gene therapy makes it possible to engineer tumor-specific T-cells by chimeric antigen receptors (CARs) or TCRs, and those engineered T-cells have demonstrated powerful anti-tumor 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, the consortium has developed an high-throughput strategy to identify high affinity tumor-specific TCRs. With this strategy they did identify such TCRs:  1) TCRs specific for PRAME, recognising a high variety of cancers, and 2) TCRs specific for the B-cell transcription factor BOB1, that exert highly potent reactivity against different B-cell malignancies, including multiple myeloma. Clinical studies with these different tumor-specific TCRs will be initiated in coming years by Bellicum Pharmaceuticals.

This project has identified novel high affinity TCRs directed against different tumor-associated antigens, leading to a broadening of the treatment of cancer patients with TCR gene therapy. Currently, they are exploring the possibility to initiate TCR gene therapy studies with different commercial partners to develop effective medicines for cancer patients leading to a cure for cancer patients or to prevent cancer progression and thereby improving the quality of life of these patients.

Picture: Courtesy of C.P. Ho