(Reaction Biology) Humanized PD-1 knock-in mice as a model system for combination therapies with human specific PD-1 therapeutics

Introduction

Checkpoint inhibitor treatment has become a common therapy for various cancer types. As an escape mechanism, tumor cells expressPD-L1 on their surface, as a ligand for PD-1 with players of the immune system (such as T cells), aimed at preventing the immune system from exerting its anti-tumour activities. Antibodies blocking the PD-L1/PD-1 interaction have emerged as front-line treatments for various oncological indications. Several anti-PD-L1 and anti-PD-1 therapeutics are already approved and in clinical use. For preclinical testing of such human specific antibodies, syngeneic tumour models are of limited use due to the limited cross-specificity of such antibodies, giving rise to the development of humanized mouse models in which combination therapies testing new drugs with already clinically approved human checkpoint inhibitors addressing human specific targets can be evaluated.