Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy

The PD-1/PD-L1 signaling pathway plays a crucial role in cancer immune evasion, and the use of anti-PD-1/PD-L1 antibodies represents significant milestone immunotherapy. However, low response rate observed unselected patients development therapeutic resistance remain major obstacles to their clinical application. Accumulating studies showed that overexpressed TGF-β is another immunosuppressive factor apart from traditional checkpoints. Actually, effects PD-1 pathways are independent interactive, which work together contributing evasion cell. It has been verified blocking PD-L1 simultaneously could enhance efficacy monoclonal antibody overcome its treatment resistance. Based on bispecific or fusion protein technology, multiple bifunctional have developed. In preclinical studies, these updated exhibited potent anti-tumor activity, superior monotherapies. review, we summarized advances targeting We believe next-generation checkpoint inhibitors would substantially alter paradigm, especially anti-PD-1/PD-L1-resistant patients.