Immune reprogramming of cold tumors using TGF-β/PD-L1 bispecific antibody and armed oncolytic virus therapy

Immunotherapy has revolutionized oncology; however, its efficacy remains limited by the immunosuppressive tumor microenvironment (TME). This editorial synthesizes recent advances demonstrating how rationally designed combination strategies - particularly those incorporating the transforming growth factor beta/programmed death-ligand 1 (TGF-β/PD-L1) bispecific antibody platform (YM101/BiTP) and the multi-cytokine-armed oncolytic virus VG161 - can overcome resistance mechanisms. By concurrently dismantling immunosuppressive networks, activating innate immunity and remodeling the TME, these approaches show superior preclinical activity across challenging tumor phenotypes. The integration of mechanistic insights with evolving biomarker-driven strategies heralds a new era of personalized combination immunotherapy.