Abstract 1650: MPSA-AB5000: A high-throughput cell-based membrane protein screening array for accurate early-stage off-target assessment to accelerate safer antibody therapeutic development

Abstract Antibody drug development is a lengthy and complex process, often hindered by off-target binding that affects approximately 25-30% of preclinical candidates. With the growing importance of advanced modalities such as CD3 bispecific antibodies, antibody-drug conjugates (ADCs), and CAR-T therapies, early and accurate off-target assessment has become essential. However, conventional assays—including immunohistochemistry (IHC), ELISA, and flow cytometry (FACS)—remain limited in sensitivity, specificity, and throughput.To address these limitations, we developed the Membrane Protein Screening Array (MPSA-AB5000), a high-throughput, cell-based platform for comprehensive identification of antibody targets and off-targets. The MPSA-AB5000 expresses a broad spectrum of human membrane proteins in live cells, maintaining native conformation and post-translational modifications to ensure physiologically relevant binding analysis. MPSA-AB5000 is a high-throughput, cell-based platform for identifying antibody targets and off-targets, enhancing antibody specificity screening and reducing development risks. To provide the highest level of sensitivity, MPSA-AB5000 uses luciferase reporter cell line detection. The wash-free strategy reduces false negatives, and signal amplification makes remarkable discrimination. Furthermore, the platform integrates a Protein A-based reporter system, leveraging Protein A’s strong Fc-binding affinity—particularly for human IgG1, IgG2, and IgG4—to immobilize antibodies on reporter cells. This allows detection of off-target-induced signaling even in Fc-modified formats such as IgG1-LALA or IgG4. Collectively, the MPSA-AB5000 provides a robust, versatile, and physiologically relevant solution for antibody target deconvolution and specificity evaluation, accelerating the discovery and optimization of safer antibody therapeutics. Citation Format: Liping Wang, Guoqian Wang, Yao Peng, Jinying Ning, Feng Hao, . MPSA-AB5000: A high-throughput cell-based membrane protein screening array for accurate early-stage off-target assessment to accelerate safer antibody therapeutic development abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1650.