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

SIMPLE SUMMARY: Multiple Myeloma (MM) is the second most common hematological malignancy in the world. The current two US Food and Drug Administration (FDA)-approved anti-BCMA chimeric antigen receptor (CAR)-T cells therapies for MM treatment rely on patients’ own peripheral blood T cells and can only be used for those patients. This type of personalized treatment has several limitations, including high costs, long manufacturing times, and possible manufacturing failure. To solve these problems, in this review, we introduced the possibility of applying other immune cells to equip anti-BCMA CARs to treat MM, which could potentially achieve the goal of “off-the-shelf”. Although many of these therapies are still in early development, some of them have already entered the clinical trial stage and shown promising results in terms of safety and patient survival. 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.