Abstract
Bispecific peptides represent an emerging therapeutic platform in immunotherapy, offering simultaneous engagement of two distinct molecular targets to enhance specificity, functional synergy, and immune modulation. Their compact structure and modular design enable precise interaction with protein-protein interfaces and shallow binding sites that are otherwise difficult to target. This review summarizes current design strategies of bispecific peptides, including fused, linked, and self-assembled architectures, and elucidates their mechanisms in bridging tumor cells with immune effector cells and blocking immune checkpoint pathways. Recent developments highlight their potential applications not only in oncology but also in autoimmune and infectious diseases. Key translational challenges, including proteolytic stability, immunogenicity, delivery barriers, and manufacturing scalability, are discussed, along with emerging peptide engineering and computational design strategies to address these limitations. Bispecific peptides offer a versatile and adaptable platform poised to advance precision immunotherapy and expand therapeutic options across immune-mediated diseases.