title: The Efficacy of Oncolytic Adenovirus Is Mediated by T-cell Responses against Virus and Tumor in Syrian Hamster Model.
abstract: OBJECTIVE
  Oncolytic adenoviruses (Ad) represent an innovative approach to cancer therapy. Its efficacy depends on multiple actions, including direct tumor lysis and stimulation of antiviral and antitumor immune responses. In this study, we investigated the roles of T-cell responses in oncolytic adenoviral therapy.
  
  
  METHODS
  An immunocompetent and viral replication-permissive Syrian hamster tumor model was used. The therapeutic mechanisms of oncolytic Ad were investigated by T-cell deletion, immunohistochemical staining, and CTL assay.
  
  
  RESULTS
  Deletion of T cells with an anti-CD3 antibody completely demolished the antitumor efficacy of oncolytic Ad. Intratumoral injection of Ad induced strong virus- and tumor-specific T-cell responses, as well as antiviral antibody response. Both antiviral and antitumor T-cell responses contributed to the efficacy of oncolytic Ad. Deletion of T cells increased viral replication and extended the persistence of infectious virus within tumors but almost abrogated the antitumor efficacy. Preexisting antiviral immunity promoted the clearance of injected oncolytic Ad from tumors but had no effect on antitumor efficacy. Strikingly, the repeated treatment with oncolytic Ad has strong therapeutic effect on relapsed tumors or tumors insensitive to the primary viral therapy.
  
  
  CONCLUSIONS
  These results demonstrate that T cell-mediated immune responses outweigh the direct oncolysis in mediating antitumor efficacy of oncolytic Ad. Our data have a high impact on redesigning the regimen of oncolytic Ad for cancer treatment. Clin Cancer Res; 23(1); 239-49. ©2016 AACR.
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Li
authors.affiliation: National Centre for International Research in Cell and Gene Therapy, Sino-British Research Center for Molecular Oncology, Zhengzhou University, Zhengzhou, China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xuexiang
authors.initials: X
authors.lastname: Du
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Huang
authors.affiliation: National Centre for International Research in Cell and Gene Therapy, Sino-British Research Center for Molecular Oncology, Zhengzhou University, Zhengzhou, China.|Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
authors.forename: Yaohe
authors.initials: Y
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. sdwang@moon.ibp.ac.cn.
authors.forename: Shengdian
authors.initials: S
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D045744:Cell Line, Tumor; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008212:Lymphocyte Depletion; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*; D014780:Viruses / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000914:Antibodies, Viral