Humanized avian embryo models replicate an immune tumor environment for rapid immunotherapy studies.

Abstract

Re-arming the immune system to fight cancer holds significant promise. However, models enabling the rapid and reliable evaluation of immunotherapies on patient tumors are still lacking. Here, we report a humanized version of the avian model for cell and patient-derived xenograft models, which involves the creation of miniature replicas of patient and cell line-derived tumors in avian embryo tissues. Leveraging this unique technology, we developed two approaches: co-micro-implantation of human PBMCs and cancer cells or implantation of cancer cells followed by the intravenous injection of human PBMCs. By combining whole-embryo light sheet microscopy, analysis of immune cell molecular markers and evaluation of anti-PD-1 therapy in solid tumor models, we demonstrate that the humanized AVI technology recapitulates an immune microenvironment, enables the rapid screening of immune-based therapeutic strategies and supports patient response stratification for biomarker discovery.