This study introduces ATOR-1015, a human IgG1 bispecific antibody targeting CTLA-4 and OX40, designed to enhance tumor-directed immune activation. In vitro assays demonstrated that ATOR-1015 effectively activates T cells and depletes regulatory T cells (Tregs). In vivo, using human OX40 transgenic (Knockin) mice with established syngeneic tumors, ATOR-1015 treatment reduced tumor growth, improved survival, and induced long-term immunological memory. The antibody localized to the tumor microenvironment, decreased Treg frequency, and increased the number and activation of CD8+ T cells. Additionally, ATOR-1015 enhanced responses to PD-1 inhibition, suggesting its potential as a next-generation CTLA-4 targeting therapy with improved efficacy and reduced toxicity.
ATOR-1015 induces T-cell activation and Treg depletion, reduces tumor growth, improves survival, and enhances the response to PD-1 inhibition in multiple syngeneic tumor models.
Human OX40 transgenic (Knockin) mice with established syngeneic tumors
Cancer immunotherapy, Bispecific antibody, CTLA-4, OX40, Treg depletion, T-cell activation
Human OX40 transgenic Knockin model, Syngeneic tumor models, Bispecific antibody therapy
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