title: A human programmed death-ligand 1-expressing mouse tumor model for evaluating the therapeutic efficacy of anti-human PD-L1 antibodies.
abstract: Huge efforts have been devoted to develop therapeutic monoclonal antibodies targeting human Programmed death-ligand 1 (hPD-L1) for treating various types of human cancers. However, thus far there is no suitable animal model for evaluating the anti-tumor efficacy of such antibodies against hPD-L1. Here we report the generation of a robust and effective system utilizing hPD-L1-expressing mouse tumor cells to study the therapeutic activity and mode of action of anti-human PD-L1 in mice. The model has been validated by using a clinically proven hPD-L1 blocking antibody. The anti-hPD-L1 antibody treatment resulted in potent dose-dependent rejection of the human PD-L1-expressing tumors in mice. Consistent with what have observed in autochthonous mouse tumor models and cancer patients, the hPD-L1 tumor bearing mice treated by anti-hPD-L1 antibody showed rapid activation, proliferation and reinvigoration of the cytolytic effector function of CD8+T cells inside tumor tissues. Moreover, anti-hPD-L1 treatment also led to profound inhibition of Treg expansion and shifting of myeloid cell profiles, showing bona fide induction of multilateral anti-tumor responses by anti-hPD-L1 blockade. Thus, this hPD-L1 mouse model system would facilitate the pre-clinical investigation of therapeutic efficacy and immune modulatory function of various forms of anti-hPD-L1 antibodies.
authors.affiliation: Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 200005, China.|Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
authors.forename: Anfei
authors.initials: A
authors.lastname: Huang
authors.affiliation: Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 200005, China.|Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
authors.forename: Di
authors.initials: D
authors.lastname: Peng
authors.affiliation: Mabspace Biosciences (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 200005, China.|Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Ben
authors.affiliation: Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 200005, China.|Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 200005, China.|Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yang
authors.affiliation: Mabspace Biosciences (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Teng
authors.affiliation: Mabspace Biosciences (Suzhou) Co., Ltd, Suzhou, 215123, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Qian
authors.affiliation: Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, 200005, China.|Suzhou Institute of Systems Medicine, Suzhou, 215123, China.
authors.forename: F Xiao-Feng
authors.initials: FX
authors.lastname: Qin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000074322:Antineoplastic Agents, Immunological; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human