A next-generation anti-CTLA-4 probody mitigates toxicity and enhances anti-tumor immunity in mice.

ABSTRACT: CTLA-4 is a promising target for immune checkpoint inhibition in cancer therapy, with CTLA-4 blockade achieving prolonged overall survival for responding patients. However, the progressively elevated doses of anti-CTLA-4 agents, aimed at achieving better efficacy, result in increased toxicities, limiting their clinical applications. Here, we generate a prodrug design of the anti-CTLA-4 antibody, named ProCTLA-4, by folding the Fab fragment of the antibody in a tumor-associated protease-based manner. In preclinical mouse models, ProCTLA-4 effectively depletes suppressive regulatory T cells within the tumor microenvironment and enhances tumor-associated antigen-specific CD8⁺ T cell responses, while exhibiting reduced toxicity compared to currently available CTLA-4 blockade approac

SUBMITTER: Cao W 

PROVIDER: S-EPMC12514261 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature