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Significance This article describes a fully human therapeutic heavy chain–only antibody for anti-tumor treatment. We show that this anti-CTLA-4 antibody, HCAb 4003-2, has advantageous properties and stimulates anti-tumor T cell… Click to show full abstract
Significance This article describes a fully human therapeutic heavy chain–only antibody for anti-tumor treatment. We show that this anti-CTLA-4 antibody, HCAb 4003-2, has advantageous properties and stimulates anti-tumor T cell activation in several ways: 1) It binds human CTLA4 with high affinity; 2) it effectively depletes tumor-resident regulatory T cells, leading to enhanced antibody-dependent cellular cytotoxicity (ADCC); 3) with its small size, it shows potent tumor penetration, thereby more widely exerting its effect on T cell activation; and 4) the enhanced efficacy combined with the shorter serum half-life and less systemic drug exposure in vivo potentially provides an improved therapeutic window in clinical applications.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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