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bioRxiv · 10.1101/2025.09.04.673944

Proteome integral solubility alteration assay for monitoring antibody-antigen cell interactions

Zubarev, R. A.·Gaetani, M.·Lundstrom, S. L.·Lu, W.·Hou, Y.·Haeggstrom, J. Z.·Mukherjee, S.
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Abstract

The Proteome Integral Solubility Alteration (PISA) assay is commonly used to identify and characterize interactions between small molecules and the cellular proteome. In this study, a modified PISA approach identified tumor necrosis factor alpha (TNF) as the antigen of the monoclonal antibody infliximab in activated monocytes - uniquely among [~]8,000 cellular proteins. These results highlight the potential of PISA-based analysis not only for monitoring antibody-antigen interactions in therapeutic development, but also for identifying new antigens and characterizing the initial effector functions of antibodies within complex proteome environments. TeaserModified PISA pinpointed TNF- as Infliximabs antigen among 8000 proteins, highlighting broad potential for therapeutic antigen studies.

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Zubarev, R. A., Gaetani, M., Lundstrom, S. L., Lu, W., Hou, Y., Haeggstrom, J. Z., Mukherjee, S.. 2025-09-06. Proteome integral solubility alteration assay for monitoring antibody-antigen cell interactions. https://doi.org/10.1101/2025.09.04.673944

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