PD-1+TCF-1+ stem-like CD8 T cells differentiate into effector T cells with enhanced anti-tumor and viral efficacy upon PD-1 cis-targeted IL-2R-agonism”

Here we show that IL-2Rbg-biased agonists are unable to preferentially expand better effector T cells in cancer models, and describe PD1-IL2v, a novel immunocytokine, that overcomes the need for CD25 binding by docking in cis to PD-1. In cis binding of PD1-IL2v to PD-1 and IL-2Rbg on the same cell recovers the ability to differentiate stem-like CD8 T cells into better effectors in the absence of CD25 binding in both chronic infection and cancer models, and provides superior efficacy. Overall design: RNA-seq