Abstract 7291: Advancing cancer immunotherapy: characterizing and leveraging bispecific antibodies targeting immune checkpoints

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Abstract Bispecific antibodies targeting immune checkpoints are transforming cancer immunotherapy by enabling novel mechanisms of action unattainable by monospecific antibodies. These engineered molecules simultaneously engage two distinct epitopes, such as PD-1 and CTLA-4 or TIGIT, to amplify anti-tumor immune responses while minimizing off-target effects. Here we demonstrate the use of cell-based reporter bioassays to provide a robust platform for assessing the functional potency, stability, and specificity of bispecific antibodies. Combination bioassays, such as PD-1 + TIGIT and PD-1 + LAG-3, evaluate synergistic effects on T-cell activation. Additionally, Fc effector function bioassays, including ADCC and ADCP assays, assess the cytotoxic potential and receptor-mediated activity of bispecific formats. These assays ensure precise characterization of mechanisms of action, guiding the refinement of antibody designs. Citation Format: Jun Wang, Denise Garvin, Jonathan Mitchell, Pete Stecha, Michael Beck, Jim Hartnett, Kai Hillman, Gopal Krishnan, Frank Fan, Julia Gilden, Mei Cong, Jamison Grailer. Advancing cancer immunotherapy: characterizing and leveraging bispecific antibodies targeting immune checkpoints [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7291.

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