biostudies-literatureStrazza MNCRR NIH HHSNIAID NIH HHSNCI NIH HHSNIH HHS380-390https://www.ebi.ac.uk/biostudies/studies/S-EPMC9664140biostudies-literatureUnknown27The transmembrane adaptor phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG) is phosphorylated in T cells downstream of PD-1 signaling and contributes to the resulting functional inhibition of multiple cellular processes. Furthermore, PAG expression is negatively correlated with survival in multiple human tumors and is a driver of murine tumor growth and immune evasion. Here we develop an antibody that targets the extracellular domain of human PAG, with cross-reactivity to murine PAG. We demonstrate that this antibody binds to extracellular PAG on intact cells and affects T cell activation. Finally, we show that administration of anti-PAG monoclonal antibody in combination with anti-PD-1 antibody to mice bearing MC38 tumors limited tumor growth and enhanced T ceMolecular therapy. Methods & clinical developmentNeutralization of the adaptor protein PAG by monoclonal antibody limits murine tumor growth.PMC9664140S10 RR027050S10 OD020056R21 CA231277R01 AI150597R01 AI125640F30 CA271624Mor AAdam KAzoulay-Alfaguter IStrazza MMoore EKfalseNeutralization of the adaptor protein PAG by monoclonal antibody limits murine tumor growth.The transmembrane adaptor phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG) is phosphorylated in T cells downstream of PD-1 signaling and contributes to the resulting functional inhibition of multiple cellular processes. Furthermore, PAG expression is negatively correlated with survival in multiple human tumors and is a driver of murine tumor growth and immune evasion. Here we develop an antibody that targets the extracellular domain of human PAG, with cross-reactivity to murine PAG. We demonstrate that this antibody binds to extracellular PAG on intact cells and affects T cell activation. Finally, we show that administration of anti-PAG monoclonal antibody in combination with anti-PD-1 antibody to mice bearing MC38 tumors limited tumor growth and enhanced T ce2022-01-01T00:00:00Z2022 Dec2025-07-13T03:04:52.092Z2025-04-05T11:36:03.442ZS-EPMC96641403641947110.1016/j.omtm.2022.10.012