Strategy for Constructing Prodrug-Type Bispecific Antibodies Activated by Matrix Metalloproteinases

School of Pharmacy, Hebei Medical University, 050000, Shijiazhuang, Hebei, China

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Abstract

Given the high specific expression of matrix metalloproteinases in the solid tumor microenvironment, they serve as an ideal endogenous triggering mechanism for the tumor-selective activation of antibody drugs This paper systematically summarizes the construction strategies of pro-drug bispecific antibodies (Pro-BsAb) based on the MMP activation mechanism, with a focus on their molecular design paradigms and therapeutic progress in preclinical solid tumor models The results indicate that Pro-BsAb restores antibody function through tumor microenvironment-specific cleavage, significantly enhancing tumor enrichment and reducing systemic toxicity. Among these, linker optimization, masking peptide screening, and bispecific antibody configuration selection are core factors affecting therapeutic efficacy. Currently, some candidate molecules have demonstrated good control rates in models such as breast cancer and colorectal cancer. This strategy possesses unique advantages in expanding the therapeutic window, overcoming drug resistance, and combining immunotherapy. Future research should focus on optimizing the in vivo stability of linkers and exploring the synergistic mechanisms of combination therapies to facilitate their clinical translation.