Testing BCMA CAR T-cell and B7-H3 bispecific engager combinations in multiple myeloma
Sontayananon N, Yuti P, Sawasdee N, et al. Dual Targeting of BCMA and B7-H3 With CAR T Cells and Bispecific Protein Engagers Enhances Anti-Myeloma Activity. Biomedicine and Pharmacotherapy. 2025; 193 (doi: 10.1016/j.biopha.2025.118820).
Scientists say that aiming chimeric antigen receptor (CAR) T cells at both B7-H3 and B cell maturation antigen (BCMA), which is effective alone but still vulnerable to therapeutic resistance, deepens the immunotherapy's anti-myeloma effect. Immune checkpoint upregulation is one of the primary reasons BCMA-directed CAR T-cell treatment fails, making the immune checkpoint protein B7-H3 a rational target for therapeutic intervention. Heavily expressed in multiple myeloma (MM), the protein is associated with T-cell dysfunction and unfavorable prognosis. However, pairing a recombinant anti-B7-H3/CD3 bispecific protein engager with anti-BCMA CAR T cells produces better anti-myeloma activity than either component could achieve independently, according to researchers. Dual targeting of BCMA and B7-H3 improves T-cell activation and proliferation, effector function, and cytotoxicity against MM, thereby reducing the likelihood of therapeutic resistance not only in MM but potentially in other malignancies expressing BCMA or B7-H3 as well, the researchers report.