Abstract Recent advances in cancer immunotherapy using monoclonal antibodies have dramatically revolutionized the therapeutic strategy against advanced malignancies, inspiring the exploration of various types of therapeutic antibodies. Bispecific antibodies (BsAbs) are engineered molecules designed to target two different epitopes or antigens. The mechanism of action of BsAbs can be manipulated to create variable and novel functionalities, including linking immune cells with tumor cells or signaling pathway blockade. BsAb-based therapies have demonstrated significant preclinical and clinical potential, as evidenced by the regulatory approval of molecules like blinatumomab (CD19/CD3), amivantamab (EGFR/Her3), ivonescimab (PD-1/VEGF-A), and others. Eurofins DiscoverX® provides a robust portfolio of cell-based assays for oncology targets and offers three primary assay formats to characterize BsAbs: (1) Cytotoxicity assays: To assess functional activity of BsAbs in trans, specifically for characterizing T-cell engagers (BiTEs) and similar molecules, (2) Dimerization assays: To record hetero dimerization of target receptors in cis, and (3) Pathway signaling assays: To evaluate the functional activity of each individual BsAb target arm This presentation highlights case studies illustrating the use of these cell-based assays to monitor key BsAb MOAs targeting critical tumor antigens, including CD19, PD-1, and VEGF-A. Applications will demonstrate the evaluation of BsAb-mediated tumor cell killing, rank-ordering of antibody candidates, and assessment of the function and specificity of individual BsAb arms. These assays provide essential tools for the accelerated discovery and characterization of next-generation BsAb therapeutics. Citation Format: Venkatesh Chari, Surekha Bonasu, Luhan Yang, Jennifer Lin-Jones, Jane Lamerdin, Alpana Prasad, Gaurav Agrawal, . Mechanism-driven cell-based assays to screen Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5543.
Chari et al. (Fri,) studied this question.