Fig. 1

The schematic diagram of BCMA mediated signal conduction and immunotherapeutic strategies targeting BCMA in MM. BCMA is one of the most specific antigens in MM, which is closely related to transmembrane protein BAFF-R and TACI. BAFF binds to BCMA, BAFF-R and TACI, while APRIL binds to BCMA and TACI depending on CD138 (syndecan-1). BCMA delivers critical signal via APRIL, which regulates MEK/ERK, PI3K/AKT and NFκB pathway, to induce B-cell maturation and differentiation into plasma cells. BCMA is a natural substrate for γ-secretase that forms sBCMA, which may neutralize anti-BCMA immune drug. Immune therapeutic strategies targeting BCMA include BCMA-targeted vaccines, anti-BCMA antibodies (such as ADCs, RITs and BsAbs) and BCMA-targeted CAR cells including autologous or allogeneic BCMA CAR T cells, dual-antigen targeting CAR T-cell strategies and BCMA CAR on other cells. Representative therapies discussed in the review are listed. BCMA: B cell maturation antigen; APRIL: A proliferation-inducing ligand; BAFF: B-cell activating factor; BAFF-R: B-cell activating factor receptor; TACI: Transmembrane activator and calcium modulator and cyclophilin ligand interactor; sBCMA: Soluble BCMA; mAbs: Monoclonal antibodies; ADCs: Monoclonal antibodies bound to toxic drug; RITs: Recombinant immunotoxins; BsAbs: Bispecific antibodies; CAR: Chimeric antigen receptor; CTL: Cytotoxic T-cell