Abstract NG11: Autologous humanized PDX modeling for immuno-oncology recapitulates the human tumor microenvironment

• Published in: Cancer research (Chicago, Ill.) Ill.), 2023-04, Vol.83 (7_Supplement), p.NG11-NG11
• Main Authors: Chiorazzi, Michael, Martinek, Jan, Krasnick, Bradley, Zheng, Yunjiang, Robbins, Keenan, Qu, Rihao, Kaufmann, Gabriel, Skidmore, Zachary, Henze, Laura, Brösecke, Frederic, Adonyi, Adam, Zhao, Jun, Shan, Liang, Sefik, Esen, Mudd, Jacqueline, Bi, Ye, Goedegebuure, S Peter, Griffith, Malachi, Griffith, Obi, Oyedeji, Abimbola, Fertuzinhos, Sofia, Garcia-Milian, Roland, Boffa, Daniel, Detterbeck, Frank, Dhanasopon, Andrew, Blasberg, Justin, Judson, Benjamin, Gettinger, Scott, Politi, Katerina, Kluger, Yuval, Palucka, A Karolina, Fields, Ryan, Flavell, Richard A.
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-NG11

The immune milieu within tumors, consisting of diverse cell types including adaptive immune cells as well as macrophages, dendritic cells, natural killer and other innate immune cells, is critical to determining cancer outcome. However, the immune tumor microenvironment (TME) has been challenging to model, owing to inherent inter-species differences. While humanized mice can support human immune cells, the hematopoietic stem and progenitor cells (HSPCs) used for transplantation have been largely limited to fetal or neonatal stem cell sources, necessitating allogeneic experiments with limited applicability. We sought to develop a method to pre-clinically model an individual adult cancer patient, capturing the unique features of an individual such as germline genetic determinants of immune function and somatic tumor heterogeneity, and creating an autologous system. MISTRG6 may be engrafted with low numbers of HSPCs. When engrafted with equivalent numbers of CD34+ cells from human fetal liver (FL), neonatal cord blood (CB), adult mobilized peripheral blood (MPB), or adult bone marrow (BM), MISTRG6 mice harbored greatly increased human hematopoietic cells as a proportion of total hematopoietic cells in peripheral blood compared with NOD-scid-gamma (NSG) and MISTRG mice (p