SITC 2019 – Development of a peripheral blood mononuclear cells (PBMC) Immunograft® platform to evaluate the pharmacodynamics of immuno-oncology therapeutics
Development of a peripheral blood mononuclear cells (PBMC) Immunograft® platform to evaluate the pharmacodynamics of immuno-oncology therapeutics
BhBhavna Verma1, Bruce Ruggeri1, and Amy Wesa1
1Champions Oncology, Rockville, MD, USA.
Humanized immune system (HIS) mouse models enable in vivo studies in the context of the human immune cells with a human tumor and are critical for the development of next generation immune-oncology (IO) agents. Humanization of immunodeficient mice through the adoptive transfer of normal adult PBMC leads to rapid engraftment of human T cells to study immune-modulatory agents in the context of human tumor xenografts, but is limited by the development of xenogeneic graft-versus host disease (xGVHD). In this study, we evaluated the engraftment of PBMC in β2microglobulin null super-immunodeficient mice NSG-B2M mice, that lack MHC Class I on host tissues. A cell line-derived xenograft model (CDX) co-engrafted with PBMC (PBMC-ImmunoGraft) was characterized for humanization, tumor infiltrating leukocytes (TIL) phenotype and tumor response to checkpoint inhibitors.