Abstract PHB02: Impact of genetic diversity on the growth of human-derived xenografts

Abstract

Abstract The generation of human patient-derived xenograft (hPDX) models, and efficacy testing on human cell-derived xenografts (hCDX) or hPDX, are usually performed on a single mouse genetic background. Emerging evidence suggests that host genetic background underlies the variability in xenograft establishment as well as tumor response to drugs. Here we show two approaches, a genetic and a chemical one, on human-derived xenografts as proof of concept to show that xenografting can be done in genetic diverse mice and growth kinetics is different depending on the strain of the mice. The genetic approach is to use Rag1-/- mice for xenografts—Rag1-/- mice are immunodeficient and accept human cells. We found that the growth kinetics of a well-characterized hCDX is unequivocally distinct in three genetically diverse strains. The chemical approach is to use 2-deoxy glucose (2DG) to dampen the immune system in order to reduce graft rejection. We found that the growth kinetics and engraftment acceptability rates of a well-characterized hPDX were highly unique in eight genetically distinct outbred mice treated with 2DG. These findings provide proof of concept that xenografting can be conducted in genetically diverse mice. Development of these novel platforms will provide the genetic diversity necessary for the growth of any type of tumor, expanding the PDX platform to sustain cancers that have previously failed to xenograft. This abstract is also being presented as Poster B33. Citation Format: Jennifer Sargent, Roberto Cartagena, Stephanie Trowbridge, Steven Munger, Muneer Hasham. Impact of genetic diversity on the growth of human-derived xenografts [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr PHB02.