An improved cell line-derived xenograft humanized mouse model for evaluation of PD-1/PD-L1 blocker BMS202-induced immune responses in colorectal cancer

Abstract

The establishment of an in vivo mouse model mimicking human tumor-immune environments provides a promising platform for immunotherapy assessment, drug discovery and clinical decision guidance. To this end, we construct humanized NCG mice by transplanting human hCD34+ hematopoietic progenitors into non-obese diabetic (NOD) Cg-PrkdcscidIL2rgtm1Wjl/Sz (null; NCG) mice and monitoring the development of human hematopoietic and immune systems (Hu-NCG). The cell line-derived xenograft (CDX) Hu-NCG mouse models are set up to assess theoutcomeofimmunotherapymediatedbythesmallmoleculeBMS202.AsaPD-1/PD-L1blocker,BMS202shows satisfactory antitumour efficacy in the HCT116 and SW480 xenograft Hu-NCG mouse models. Mechanistically, BMS202 exerts antitumour efficacy by improving the tumor microenvironment and enhancing the infiltration of hCD8+ T cells and the release of hIFNγ in tumor tissue. Thus, tumor-bearing Hu-NCG mice are a suitable and important in vivo model for preclinical study, particularly in cancer immunotherapy.