Humanized mouse models for preclinical evaluation of novel immune therapies, checkpoint inhibitors and immune cell engagers

Background: The preclinical evaluation of novel immune therapies demands humanized mouse models with functional human cells. In previous studies we have established a system T- B- and NK cells, as well monocytes in immunodeficient mice by transfer hematopoietic stem cells (HSCs) or peripheral blood mononuclear (PBMC). By transplantation cell-line-derived (CDX) patient-derived (PDX) tumor xenografts on mice, successfully generated full tumor-immune-cell model for different entities. Finally, validated the functionality these using checkpoint inhibitors cell engagers. Methods: HSC-humanized were single i.v. CD34+ to NOG mice. Engraftment was monitored FACS analysis samples. CDX PDX from entities transplanted PBMC isolated NK-cell preparations used humanize multiple injections into tumor-bearing simultaneous transplantation. These evaluate inhibitors. Blood samples analysed immunohistochemistry infiltration activation. Results: HSCs engrafted differentiated proliferating Up 20% T characterized high PD-1 expression 14 weeks after HSC inoculation. Selected tumors without significant differences growth compared non-humanized Checkpoint inhibitor treatments induced delay selected models. xenograft revealed an increased percentage tumor-infiltrating addition, identified set interference parallel injection PBMC, engagers other therapeutics. Conclusions: We combination donor derived subsets effector demonstrated successful engraftment strains generating hematopoiesis. been employed Our allow preclinical, translational biology new therapies, drug combinations biomarker identification validation. No conflict interest.