Non-Conventional Allogeneic Anti-BCMA Chimeric Antigen Receptor-Based Immune Cell Therapies for Multiple Myeloma Treatment

Abstract

MM, characterized by the progressive accumulation of clonal plasma cells in bone marrow, remains a severe medical problem globally. Currently, almost all MM patients who have received standard treatments will eventually relapse. Autologous anti-BCMA CAR-T cells are one of the FDA-approved immunotherapy cell-based products for treating adults with relapsed or refractory (r/r) multiple myeloma. However, this type of CAR-T cell product has several limitations, including high costs, long manufacturing times, and possible manufacturing failure, which significantly hinder its wider application for more patients. In this review, we summarized the current development stage of applying other types of immune cells to bring the anti-BCMA CAR-T therapy from autologous to allogeneic. In general, anti-BCMA CAR gene-edited αβ T cells and CAR-Natural Killer (NK) cells are at the forefront, with multiple clinical trials ongoing, while CAR-γδ T cells and CAR-invariant Natural Killer T (iNKT) cells are still in pre-clinical studies. Other immune cells such as macrophages, B cells, and dendritic cells have been mainly developed to target other antigens and have the potential to be used to target BCMA. Nevertheless, additional regulatory requirements might need to be taken into account in developing these non-conventional allogenic anti-BCMA CAR-based cell products.

Keywords: anti-BCMA CAR; clinical regulations; immune cells; multiple myeloma; non-conventional; off-the-shelf.

Figure 1

Allogeneic and autologous adoptive transfer of CAR-based immune cells.

Figure 2

The general cell manufacturing process of gene edited-αβ T cells.

Figure 3

The current development stages of major types of anti-BCMA CAR-based immune cells.