PO.ET02.05 · 实验与分子治疗
MPSA-AB5000: A high-throughput cell-based membrane protein screening array for accurate early-stage off-target assessment to accelerate safer antibody therapeutic development
作者与单位
摘要 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.
利益披露 Disclosure
L. Wang,
Kyinno Biotechnology Co., LTD Employment.
G. Wang,
Kyinno Biotechnology Co., LTD Employment.
Y. Peng,
Kyinno Biotechnology Co., LTD Employment.
J. Ning,
Kyinno Biotechnology Co., LTD Employment.
F. Hao,
Kyinno Biotechnology Co., LTD Employment.