Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids.
Firas HamdanErkko O YlösmäkiJacopo ChiaroYvonne GiannoulaMaeve LongManlio FuscielloSara FeolaBeatriz MartinsMichaela FeodoroffGabriella AntignaniSalvatore RussoOtto KariMoon LeePetrus JärvinenHarry NisenAnna KreutzmanJeanette H W LeusenMohamed El MissiryThomas G McWilliamsMikaela GrönholmVincenzo CerulloPublished in: Journal for immunotherapy of cancer (2022)
Arming PD-L1 checkpoint inhibitors with Fc-effector mechanisms of both an IgA1 and an IgG1 can increase efficacy while maintaining safety by limiting expression to the tumor using oncolytic adenovirus. The increase in tumor killing is mostly attributed to the activation of multiple effector populations rather than activating a single effector population leading to significantly higher tumor killing.