ArticleJournal of medicinal chemistry2025
Development of Optimized Exatecan-Based Immunoconjugates with Potent Antitumor Efficacy in HER2-Positive Breast Cancer.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Novel Camptothecin-Based Lipid Conjugated with Steroids and Triterpene Acids: Enhanced Cellular Uptake and Topoismerase I Inhibition.Pharmaceutics · 2026Article
- Precision theranostics in oncology: integrating antibody-drug conjugates, radioimmunotherapy, and immuno‑PET for adaptive cancer care.Discover oncology · 2026Review
- Antibody-Empowered Nanomedicine for Precise Biomedical Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has significantly improved with the advent of anti-HER2 therapies, especially antibody-drug conjugates (ADCs). In this field, ADCs, like trastuzumab deruxtecan (T-DXd), using camptothecin analogs, represent a promising strategy. However, T-DXd can induce resistance and serious adverse effects, potentially driven by a non-specific Fcγ receptor-mediated endocytosis. Here, we report the development of novel HER2-targeting conjugates, using the camptothecin derivative exatecan and a linker optimized to control hydrophobicity. Three formats were evaluated: a high drug-to-antibody ratio (DAR) 8 IgG-based ADC (IgG(8)-EXA), and two DAR 4 Fc-free constructs (Mb(4)-EXA and Db(4)-EXA). Thus, IgG(8)-EXA and Mb(4)-EXA displayed potent, specific cytotoxicity against HER2-positive breast cancer cells and strong antitumor activity in vivo
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