Chimeric Antigen Receptor T Cell Therapy and Its Significance in Multiple Myeloma

Abstract

Multiple myeloma (MM) has a five-year prevalence worldwide of 230,000 people and is known as the second most common hematological malignancy within the United States. Extensive research has been conducted to gain a wide range of treatment strategies, providing hope to these patients. Combination therapy using chemotherapy, monoclonal antibodies, and immunomodulatory drugs are the current management of choice. After the introduction of chimeric antigen receptor (CAR) T cell therapy, promising results have been evidenced. In this therapy, T cells are derived from the patient and modified in-vitro to induce receptors that later target specific antigens when they are injected into patients. CAR T cells use three mechanisms to kill tumor cells: cytolytic pathways, cytokine release, and Fas/FasL axis. In this review, we highlight the different tumor markers targeted for therapy against multiple myeloma (MM). Target antigens for CAR T cell therapy include B-cell maturation antigen (BCMA), signaling lymphocyte activation molecule F7 (SLAMF7), CD38, CD138, CD19, immunoglobulin kappa light chain, orphan G protein-coupled receptor class C group 5 member D (GPRC5D). With the benefit of improving survival and prognosis, this therapy does carry a risk of some adverse events such as cytokine release syndrome, encephalopathy, infections, hypogammaglobulinemia, and tumor lysis syndrome.

From spear to trident: Upgrading arsenal of CAR-T cells in the treatment of multiple myeloma

“…Recently, the use of chimeric antigen receptor engineered T-cell therapy (CAR-T) has shown great promise in the treatment of MM, including approaches targeting B-cell maturation antigen (BCMA) [ 52 ], CD138 [ 53 ], CD19 [ 54 ], orphan G protein-coupled receptor, class C group 5 member D (GPRC5D) [ 55 ], which showed significantly improved activity, including a sustained and profound response. For targets currently being investigated in preclinical or clinical trials for MM, see the comprehensive review by previous researchers [ [56] , [57] , [58] ] where the authors provided a comprehensive overview of CAR-T targets for MM, which include CD138, CD38, CS1, CD19, kappa light chain, CD56, CD44v6, Lewis Y, NY-ESO-1, CD229 ( Table 1 ). Therefore, we omit this information here to avoid repeating its already published content.…”