Antibody peptide conjugates as multifunctional therapeutics: Mechanisms, challenges, and prospects

Antibody peptide conjugates (APCs) represent a newly emerging class of targeted biotherapeutics that embody a novel structural paradigm by combining the precise targeting capabilities of antibodies with the versatile biological functions of peptides. APCs not only overcome the inherent limitations of conventional peptide therapeutics but also go beyond the cytotoxicity-focused paradigm of traditional antibody drug conjugates (ADCs). By flexibly combining peptide payload activities with antibody functions, APCs have developed into diverse therapeutic strategies, including immunomodulation, targeted antibacterial, and targeted protein degradation, among others. Several APCs have already achieved notable progress and entered clinical studies, underscoring their potential as a next-generation targeted therapeutic platform. In this review, we present the first comprehensive structural framework for APCs, defining seven distinct subtypes and discussing their biological mechanisms, structure-activity relationships, recent advances, and major challenges. Furthermore, we propose guiding principles for the rational design of APCs and highlight future research directions, aiming to accelerate progress in this rapidly developing field of innovative therapeutics.