Fc-null anti-PD-1 monoclonal antibodies deliver optimal checkpoint blockade in diverse immune environments.
Julia Moreno-VicenteJane E WilloughbyMartin C TaylorSteven G BoothVikki L EnglishEmily L WilliamsChristine A PenfoldC Ian MockridgeTatyana InzhelevskayaJinny KimH T Claude ChanMark S CraggJuliet C GrayStephen A BeersPublished in: Journal for immunotherapy of cancer (2022)
Our data collectively support a critical role for Fc:FcγR interactions in inhibiting immune responses to both mouse and human anti-PD-1 mAbs, and highlight the context-dependent effect that anti-PD-1 mAb isotypes can have on T-cell responses. We propose that engineering of Fc-null anti-PD-1 mAbs would prevent FcγR-mediated resistance in vivo and allow maximal T-cell stimulation independent of the immunological environment.