T-cell engager bispecific antibodies enable T cells to eliminate Multiple Myeloma by targeting tumor CD38 in combination with PD-L1

Abstract Bispecific antibodies have gradually been applied in the treatment of multiple myeloma(MM). The combination of bispecific antibodies targeting CD3 and CD28 mimics the dual-signaling system (antigen signaling and co-stimulatory signaling) of natural T cell activation, thereby significantly enhancing the anti-tumor response of T cells. CD38, a transmembrane glycoprotein, is highly expressed on MM cells and serves as an important surface marker. Meanwhile, PD-L1, an immunosuppressive molecule, is associated with poor prognosis in MM patients. Leveraging these biological insights, this study systematically evaluated the capacity of bispecific antibodies to eliminate MM cells via T-cell activation, employing comprehensive in vitro functional assays and in vivo murine models. Notably, in vitro data revealed that a bispecific antibody simultaneously engaging PD-L1 (to counteract immune suppression) and CD38 (to direct T-cell cytotoxicity) exhibited markedly enhanced antitumor efficacy—even under conditions of reduced CD38 surface expression on MM cells. Nevertheless, the translational relevance of this combinatorial mechanism requires further validation in preclinical in vivo settings.