Protein and peptide letters · 2026
CD44v6- and VEGFR2-targeting antibody-drug conjugates: Enhancing precision and safety in cancer therapy through a dual-targeting strategy.
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Wu Menghuai, Feng Xuezhe, Huang Wenqiang, Wu Ye, Cui Juanjuan
Аннотация
BACKGROUND: Bispecific antibody-drug conjugates (BsADCs) represent a promising therapeutic strategy to overcome single-target resistance. Here, we developed a dual-targeting BsADC that simultaneously recognizes CD44v6 and VEGFR2.
METHODS: Spatial configurations were optimized in CHO expression systems. In vitro binding affinities and cytotoxicity were evaluated alongside in vivo anti-tumor efficacy and systemic toxicity in xenograft models.
RESULTS: The variant BIWA8-(G4S)2-DC101-scFv exhibited high stability and an SEC purity of 84.6%. The construct retained antigen-binding affinity and mediated dose-dependent cytotoxicity in vitro. In mouse xenograft models, the dual-targeting BsADC showed potential anti-tumor activity compared to single-target controls, with no overt body weight loss or observable physical toxicity detected during treatment.
CONCLUSION: These findings suggest that the CD44v6/VEGFR2-targeting BsADC represents a potential candidate for targeted cancer therapy.
LIMITATIONS: High-resolution LC-MS characterization for absolute DAR distribution and long-term toxicity evaluations in non-human primates were not performed in this preliminary work.
METHODS: Spatial configurations were optimized in CHO expression systems. In vitro binding affinities and cytotoxicity were evaluated alongside in vivo anti-tumor efficacy and systemic toxicity in xenograft models.
RESULTS: The variant BIWA8-(G4S)2-DC101-scFv exhibited high stability and an SEC purity of 84.6%. The construct retained antigen-binding affinity and mediated dose-dependent cytotoxicity in vitro. In mouse xenograft models, the dual-targeting BsADC showed potential anti-tumor activity compared to single-target controls, with no overt body weight loss or observable physical toxicity detected during treatment.
CONCLUSION: These findings suggest that the CD44v6/VEGFR2-targeting BsADC represents a potential candidate for targeted cancer therapy.
LIMITATIONS: High-resolution LC-MS characterization for absolute DAR distribution and long-term toxicity evaluations in non-human primates were not performed in this preliminary work.