“Built‐in” PD‐1 blocker to rescue NK‐92 activity from PD‐L1–mediated tumor escape mechanisms

Success of adoptive cell therapy mainly depends on the ability immune cells to persist and function optimally in immunosuppressive tumor microenvironment. Although present at cancer site, become exhausted and/or inhibited, due presence inhibitory receptors such as PD-L1 malignant cells. Novel genetic strategies manipulate PD1/PD-L1 axis comprise (i) PD-1 reversion where receptor intracellular domain is replaced with an activating unit, (ii) use anti-PD-L1 CAR or (iii) disruption gene. We here alternative strategy equip therapeutic a truncated (tPD-1) abrogate PD-1/PD-L1 inhibition. show that engagement tPD-1 PD-L1-positive unleashes NK-92 activity vitro. Furthermore, this binding was sufficiently strong induce killing targets otherwise not recognized by NK-92, thus increasing range targets. In vivo treatment led reduced growth improved survival. Importantly, did interfere recognition negative conditions. Thus, represents straightforward method for improving antitumor immunity revealing new through positivity.