03.22.22

Targeting Cancer-Associated Fibroblasts in Multiple Myeloma

Sakemura R, Hefazi M, Siegler EL, et al. Targeting Cancer-Associated Fibroblasts in the Bone Marrow Prevents Resistance to CART-Cell Therapy in Multiple Myeloma. Blood. 2022; (doi: 10.1182/blood.2021012811).

Researchers report a novel strategy to block resistance to chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM) by targeting both malignant plasma cells and the cancer-associated fibroblasts (CAFs) in the tumor microenvironment. They used MM models to evaluate the effects of CAFs on CAR T-cell efficacy and create ways to overcome CAR-T cell inhibition. Their studies found that CAFs — which express molecules such as fibroblast activation protein and SLAMF7 — inhibit CAR-T cell anti-tumor activity while also promoting MM progression. In an effort to counter the CAR-T cell inhibition from the CAFs, the researchers produced CAR-T cells that target both CAFs and MM cells — a strategy that substantially increased the CAR-T cells' effector functions.

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