Cancer Immunology Research current issue

Cancer Immunology Research current issue

Research Articles XCL1 / Glypican-3 Fusion Gene Immunization Generates Potent Antitumor Cellular Immunity and Enhances Anti–PD-1 Efficacy Kun Chen , Zhiyuan Wu , Hong Zhao , Yanmei Wang , Yutong Ge , Dongmei Wang , Zhengjiang Li , Changming An , Yuying Liu , Feifei Wang , Xinyu Bi , Hongying Wang , Jianqiang Cai , Chunhong Ma and Chunfeng Qu Kun Chen State Key Lab of Molecular Oncology & Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. ORCID record for Kun Chen Zhiyuan Wu State Key Lab of Molecular Oncology & Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Hong Zhao Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Yanmei Wang State Key Lab of Molecular Oncology & Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Yutong Ge Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong University School of Basic Medicine, Jinan, China. ORCID record for Yutong Ge Dongmei Wang State Key Lab of Molecular Oncology & Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Zhengjiang Li Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Changming An Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Yuying Liu Department of Immunology and National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China. Search for this author on this site Feifei Wang State Key Lab of Molecular Oncology & Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Xinyu Bi Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Hongying Wang State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Jianqiang Cai Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for this author on this site Chunhong Ma Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong University School of Basic Medicine, Jinan, China. ORCID record for Chunhong Ma Chunfeng Qu State Key Lab of Molecular Oncology & Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below. Abstract Cancer vaccines can amplify existing antitumor responses or prime naïve T cells to elicit effector T-cell functions in patients through immunization. Antigen-specific CD8 + T cells are crucial for the rejection of established tumors. We constructed XCL1-GPC3 fusion molecules as a liver cancer vaccine by linking the XCL1 chemokine to glypican-3 (GPC3), which is overexpressed in hepatocellular carcinoma (HCC). Cells expressing XCL1-GPC3 chemoattracted murine XCR1 + CD8α + dendritic cells (DC) and human XCR1 + CD141 + DCs in vitro and promoted their IL12 production. After subcutaneous mXcl1-GPC3 plasmid injection, mXCL1-GPC3 was mainly detected in CD8α + DCs of mouse draining lymph nodes. XCL1-GPC3–targeted DCs enhanced antigen-specific CD8 + T-cell proliferation and induced the de novo generation of GPC3-specific CD8 + T cells, which abolished GPC3-expressing tumor cells in mouse and human systems. We immunized a murine autochthonous liver cancer model, with a hepatitis B background, with the mXcl1-GPC3 plasmid starting at 6 weeks, when malignant hepatocyte clusters formed, or at 14 weeks, when liver tumor nodules developed, after diethylnitrosamine administration. mXcl1-GPC3 –immunized mice displayed significantly inhibited tumor formation and growth compared with GPC3 -immunized mice. After mXcl1-GPC3 immunization, mouse livers showed elevated production of IFNγ, granzyme B, IL18, CCL5, CXCL19, and Xcl1 and increased infiltration of GPC3-specific CD8 + T cells, activated natural killer (NK) cells, and NKT cells. The antitumor effects of these immune cells were further enhanced by the administration of anti–PD-1. Anti-HCC effects induced by hXCL1-GPC3 were confirmed in an HCC-PDX model from 3 patients. Thus, XCL1-GPC3 might be a promising cancer vaccine to compensate for the deficiency of the checkpoint blockades in HCC immunotherapy. Footnotes Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/). Cancer Immunol Res 2020;8:81–93 Received March 21, 2019. Revision received August 14, 2019. Accepted October 24, 2019. Published first October 30, 2019. ©2019 American Association for Cancer Research. Log in using your username and password Username * Forgot your user name or password? Purchase access You may purchase access to this article. This will require you to create an account if you don't.



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