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

作　　者：Pengzhao Shang Liting Yu Shucheng Cao Changying Guo Wanheng Zhang 

机构地区：[1]School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China [2]Department of Pharmacy,the First Affiliated Hospital,and College of Clinical Medicine of Henan University of Science and Technology,Luoyang 471003,China [3]Department of Pharmacy,Binzhou Medical University,Yantai 264003,China [4]School of Engineering,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第10期1497-1506,共10页生物化学与生物物理学报（英文版）

基　　金：supported by the grant from the National Natural Science Foundation of China(No.81773028).

摘　　要：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-Prkdc scidIL2rg tm1Wjl/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 the outcome of immunotherapy mediated by the small molecule BMS202.As a PD-1/PD-L1 blocker,BMS202 shows 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 hIFNγin tumor tissue.Thus,tumor-bearing Hu-NCG mice are a suitable and important in vivo model for preclinical study,particularly in cancer immunotherapy.

关 键 词：BMS202 cancer immunotherapy cell-derived xenograft humanized mouse model PD-1/PD-L1 blocker 

分 类 号：R735.37[医药卫生—肿瘤]