Abstract
The transmembrane adaptor phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG) is phosphorylated in Tcells 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 humanPAG, with cross-reactivity to murine PAG. We demonstrate that this antibody binds to extracellular PAG on intact cells and affects Tcell 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 Tcell infiltration to tumors.
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