Chimeric antigen receptor T cells secreting IL-12 and anti-IL-6 to enhance responses in multiple myeloma

Description

The study aims to enhance the efficacy of chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma (MM) by engineering CAR-T cells to secrete interleukin-12 (IL-12) and an anti-IL-6 single domain antibody (sdAb). While current CAR-T therapies targeting BCMA show promising response rates, median progression-free survival remains short, indicating the need for improved strategies. The hypothesis is that the engineered CAR-T cells will repolarize microenvironment macrophages and myeloid-derived suppressor cells, thereby enhancing efficacy against MM. The study plans to engineer these modified CAR-T cells and assess their function in vitro, evaluate their efficacy using myeloma cell line/macrophage co-culture systems, and characterize their efficacy and toxicity in an immunocompetent murine model of MM. This approach aims to address challenges in CAR-T cell therapy failure and improve treatment outcomes for MM patients.