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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.

2025-09-06 molecular biology
10.1101/2025.09.04.673944 bioRxiv
Show 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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