Structural Foundation of CTLA-4 antibodies: Emerging Platforms for Next-generation Cancer Immunotherapy. (PubMed, Int Immunopharmacol) - Sep 18, 2026 - "Therapeutic antibodies targeting CTLA-4, including the FDA-approved agents ipilimumab and tremelimumab, achieve checkpoint blockade through steric occlusion of the B7-binding interface, inhibition of transendocytosis, and Fc-mediated regulatory T-cell depletion...Other antibodies, including JS007, have entered clinical evaluation, while structurally characterized agents such as mipi.4 and KN044 provide preclinical and translational insights. Emerging engineering strategies, Fc-optimized variants, tumor-activated prodrug formats, bispecific antibodies, and alternative scaffolds such as nanobodies and DARPins are now translating these structural insights into next-generation therapeutics with improved selectivity and reduced immune-related adverse events. By connecting atomic-level receptor recognition to clinical outcome, this review provides a mechanistic foundation for the rational design of next-generation CTLA-4 therapeutics with improved efficacy and reduced..."
Journal • Review • Immunology • Oncology
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Dongjin Gu; Enat Mengistu Leta; Feng Wang; Geleta Negasa Binegde; Jialong Xiong; Suaad Syed
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