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Targeted cytokine is highly effective against pancreatic cancer in mice

Douglas Hanahan, Ludwig Cancer Research Lausanne
Douglas Hanahan
Melanie Tichet, Ludwig Cancer Research Lausanne
Mélanie Tichet

A study co-led by Ludwig Lausanne’s Douglas Hanahan and Mélanie Tichet evaluated the effects of an engineered immunocytokine, PD1-IL2v, in a mouse model of pancreatic neuroendocrine cancer that is resistant to immunotherapy. A Roche product composed of an anti-PD1 targeting moiety fused to an immuno-stimulatory IL-2 cytokine variant (IL2v), PD1-IL2v selectively delivers the cytokine—which can otherwise be quite toxic—to PD1-expressing T cells in the tumor microenvironment. The researchers reported in an Immunity paper in January that PD1-IL2v induced high-endothelial venules (vascular structures that promote T cell trafficking) and substantial infiltration of stem-like, tumor-reactive killer T cells into tumors. This resulted in tumor regression and enhanced survival. Combining the immunocytokine with an anti-PD-L1 checkpoint blockade antibody sustained these therapeutic effects. Douglas, Mélanie and colleagues found that the combination reprogrammed both immunosuppressive tumor-associated macrophages and the tumor vasculature to assume antigen-presenting and pro-inflammatory phenotypes and enhanced diversity of the T cell receptor repertoire. The authors suggested these results predict benefits of the combination therapy in clinical trials. Notably, Roche has launched such a trial (NCT04303858).

Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8+ T cells and reprogramming macrophages 
Immunity, 2023 January 10

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