Novel progresses of chimeric antigen receptor (CAR) T cell therapy in multiple myeloma

Abstract

Multiple myeloma (MM) is a malignant proliferative disease of plasma cells, which leads to suppressed hematopoietic and osteolytic diseases. Despite the use of traditional chemotherapy, hematopoietic stem cell transplantation (HSCT) and targeted drugs, MM still cannot be completely cured. In recent years, chimeric antigen receptor (CAR) T cells have revolutionized immunotherapy and cancer treatment. The great success of CAR-T cells in leukemia and lymphoma has promoted its development in MM. The primary requisite for developing clinically effective CAR-T cells suitable for MM is to identify the appropriate targets. In early clinical trials, CAR-T cells targeting B-cell maturation antigen (BCMA) have shown significant anti-MM activity. Currently popular targets in clinical research and preclinical research include CD138, CD38, CS1, CD19, κ light chain, CD56, CD44v6, Lewis Y, NY-ESO-1, CD229, etc.Common toxicities such as cytokine release syndrome (CRS) and neurotoxicity also occur but controllable.MM cells are mainly localized in bone marrow, therefore, the bone marrow microenvironment has a significant effect on the therapeutic effect of CAR-T cells. Targeting both MM cells and the bone marrow microenvironment is currently the most promising treatment. In this review, we provide a comprehensive overview of CAR-T cell therapy in MM, as well as outline potential targets and methods that can overcome local immunosuppression and improve the efficacy of CAR-T cells.

Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective

“…Chimeric antigen receptor T (CAR-T) cells, which are genetically modified T cells harvested from patients to express special CARs, target tumor cells and can produce remissions again for patients who are resistant to standard therapies (1). CAR-T cell therapy has demonstrated inspiring efficacy in the treatment of B-cell original malignancies and its scope of application is broadening to many other malignancies even to solid cancers (2)(3)(4)(5)(6). Nevertheless, despite its promising efficacy, adverse events such as cytokine-release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenia and B-cell aplasia have limited the application of CAR-T cell therapy (7).…”

Study on the Relationship Between the Expression of B Cell Mature Antigen and the Classification, Stage, and Prognostic Factors of Multiple Myeloma

“…And Friedman et al found that the expression level of BCMA on malignant plasma cells of MM patients is heterogeneous (14). Because of its restricted expression pattern and physiological function, BCMA is really an ideal target for MM CAR-T therapy (15,16).…”

Characterization of the Therapeutic Effects of Novel Chimeric Antigen Receptor T Cells Targeting CD38 on Multiple Myeloma

“…Anti-CD38 monoclonal antibodies such as daratumumab, have been approved by the FDA for the treatment of newly diagnosed MM (30) and relapsed/refractory MM (31). Compared with anti-CD38 monoclonal antibodies, CD38 CAR-T cells have substantially improved specificity and can induce a durable and efficient response (32). Although CD38 CAR-T cells targeting MM have been reported, there are still no approved CD38 CAR-T cell products for clinical use; thus, more novel CD38 CAR-T cell clinical treatments are needed to advance the treatment of hematological cancers.…”