Generation and characterization of anti-CD138 chimeric antigen receptor T (CAR-T) cells for the treatment of hematologic malignancies

Chimeric antigen receptor (CAR) immunotherapy is a breakthrough in cancer therapy because it allows for the in vitro re-engineering of specific T cell receptors against different types of cancer. With CARs, glycolipid and carbohydrate tumor antigens can be made recognizable by T-cells. Tumor cells become “visible” because of direct recognition by T-cell receptor and moreover CAR is a targeting mechanism that functions independent of MHC type recognition. A vast number of CARs have been developed against hematological and non-hematological malignancies, but the success rate is higher in hematological cancers. Among hematological malignancies, CAR T cells are already in clinical trials to treat B-cell malignancies. Multiple myeloma (MM) is the second most common blood cancer involving malignancy caused by cancerous plasma cells. Plasma cell myeloma (PCM) is a type of multiple myeloma where abnormal plasma cells build up in the bone marrow and lead to tumor formation in various bones of the body. These cancerous cells crowd out the normal plasma cells that help fight infections leading to impairment of immune function and kidney damage. The SEER (Surveillance, Epidemiology, and End Results) data for multiple myeloma published by the National Cancer Institute shows the average life expectancy at 4 years. Treatment for multiple myeloma is focused on therapies that could decrease the clonal plasma cell population and thus decrease the signs and symptoms of disease. There is a need for more effective therapeutic options for MM. CD138 is a cell surface protein expressed specifically on MM and plasma cells. An antibody targeted against this antigen can be successfully used to engineer CAR-T cells for MM immunotherapy. My hypothesis is that CD138 targeting CAR-T cells may have potent anti-MM activity.