SITC 2019 – Development of a peripheral blood mononuclear cells (PBMC) Immunograft® platform to evaluate the pharmacodynamics of immuno-oncology therapeutics

Title:

Development of a peripheral blood mononuclear cells (PBMC) Immunograft® platform to evaluate the pharmacodynamics of immuno-oncology therapeutics

Authors:

BhBhavna Verma1, Bruce Ruggeri1, and Amy Wesa1
1Champions Oncology, Rockville, MD, USA.

Abstract:

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.