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  • Neutralization of the adaptor protein PAG by monoclonal antibody limits murine tumor growth.

Neutralization of the adaptor protein PAG by monoclonal antibody limits murine tumor growth.

Molecular therapy. Methods & clinical development (2022-11-25)
Marianne Strazza, Emily K Moore, Kieran Adam, Inbar Azoulay-Alfaguter, Adam Mor
ABSTRACT

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 cell infiltration to tumors.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Collagenase from Clostridium histolyticum, Sigma Blend Type H, ≥1.0 FALGPA units/mg solid
Roche
DNase I, grade II, from bovine pancreas