Limiting Antigen Escape in Patients With Relapsed Multiple Myeloma
Researchers from Harvard Medical School and the University of Southern Denmark set out to uncover a way to prevent relapse of multiple myeloma due to antigen escape by dual targeting of multiple surface antigens. The results of their research (Abstract P191), which showed some antigen-specific cytotoxicity, were presented at the 2017 Society for Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, Maryland.
Marcela V. Maus, MD, PhD, Director of Cellular Immunotherapy, Cancer Center, Massachusetts General Hospital, and colleagues utilized the natural ligand for B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a proliferation-inducing ligand (APRIL), as a chimeric antigen receptor (CAR)-binding moiety. They generated CAR constructs with scFv‐based anti‐BCMA and APRIL‐based CARs bearing different hinge and transmembrane domains (CD8 or 4‐1BB), all fused to 4‐1BB and CD3 zeta. Human primary T cells were lentivirally transduced with anti–BCMA-CAR or APRIL‐based CARs.
Activation in response to BCMA-positive or TACI-positive target cells was observed in APRIL‐based CARs. Anti–BCMA-CAR was only activated in response to BCMA-positive target cells. Both BCMA and APRIL‐CD8 hinge/transmembrane CARs displayed antigen-specific cytotoxicity. Interestingly, the investigators found lower levels in cytokine production for APRIL‐based CARs compared with anti–BCMA‐CAR.