BCMA-iNKT-CAR for the Treatment of Multiple Myeloma

Description

The goal of this project was to test and characterize a BCMA targeted chimeric antigen receptor (CAR) that we expressed on invariant natural killer T cells (iNKT) for the treatment of multiple myeloma. The advantage of iNKT cells is that they do not cause GvDH, so are a potential “off the shelf” product which means they can be used as an allogeneic product. The advantages of allogeneic products are better cell fitness, reduced time to treatment, lower cost. We showed anti-myeloma efficacy of BCMA CAR-iNKT in vitro and in vivo. In vivo, the efficacy was not as good as BCMA CAR-T so we tested our hypothesis that BCMA CAR-iNKT efficacy would be improved with a long acting IL-7 (NT-I7) and found that BCMA CAR-iNKT plus NT-I7 significantly improved expansion/persistence of BCMA CAR-iNKT and in vivo efficacy. We tested the potential for BCMA CAR-iNKT to induce cytokine release syndrome (CRS) by comparing them to BCMA CART (positive control) and BCMA CAR NK-ML (negative control) and found BCMA CAR-iNKT may have an intermediate/lower propensity to induce CRS in this in vitro model.