Miles Piper, Maureen Hoen, Laurel B Darragh, Michael W Knitz, Diemmy Nguyen, Jacob Gadwa, Greta Durini, Idil Karakoc, Abby Grier, Brooke Neupert, Benjamin Van Court, Khalid N M Abdelazeem, Justin Yu, Nicholas A Olimpo, Sophia Corbo, Richard Blake Ross, Tiffany T Pham, Molishree Joshi, Ross M Kedl, Anthony J Saviola, Maria Amann, Pablo Umaña, Laura Codarri Deak, Christian Klein, Angelo D'Alessandro, Sana D Karam
In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL-2Rβ and IL-2Rγ along with decreased IL-2Rα expression. The bispecific PD1-IL2v is a PD-1-targeted IL-2 variant (IL-2v) immunocytokine with engineered IL-2 cis targeted to PD-1 and abolished IL-2Rα binding, which enhances tumor-antigen-specific T cell activation while reducing regulatory T cell (Treg) suppression. Using PD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival, along with a profound increase in tumor-infiltrating CD8+ T cell subsets with a transcriptionally and metabolically active phenotype and preferential activation of antigen-specific CD8+ T cells...
May 8, 2023: Cancer Cell