title: Redirecting adaptive immunity against foreign antigens to tumors for cancer therapy.
abstract: Immunotherapy for cancer is often limited by weak immunogenicity of tumor antigens. However, immune systems are usually strong and effective against foreign invading antigens. To test whether the destructive effect of adaptive immunity against foreign antigens can be redirected to tumors for cancer therapy, we immunized mice with adenovector expressing LacZ (Ad/CMV-LacZ). Subcutaneous syngeneic tumors were then established in the immunized animals or in naïve animals. The immune response against adenovirus or LacZ was redirected to tumors by intratumoral injection of Ad/CMV-LacZ. We found that immunization and treatment with the adenovector dramatically reduced the tumor growth rate compared with intratumoral administration of adenovector in naïve mice. Complete tumor regression was observed in about 50% of the immunized animals but not in the naïve animals. Similar effects were observed when oncolytic vaccinia virus was used to immunize and treat tumors. Lymphocyte infiltration in tumors was dramatically increased in the immunized group when compared with other groups. Moreover, immunity against parental tumor cells was induced in the animals cured with immunization and treatment with Ad/CMV-LacZ, as evidenced by the lack of tumor growth when the mice were challenged with parental tumor cells. Taken together, these results suggest that redirecting adaptive immunity against foreign antigens is a potential approach for anticancer therapy and that pre-existing immunity could enhance virotherapy against cancers.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Wenxian
authors.initials: W
authors.lastname: Hu
authors.forename: John J
authors.initials: JJ
authors.lastname: Davis
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhu
authors.forename: Fengqin
authors.initials: F
authors.lastname: Dong
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Jian
authors.initials: J
authors.lastname: Ang
authors.forename: Henry
authors.initials: H
authors.lastname: Peng
authors.forename: Z Sheng
authors.initials: ZS
authors.lastname: Guo
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D005354:Fibrosarcoma / Q000628:therapy; D015316:Genetic Therapy; D007114:Immunization; D007763:Lac Operon; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009163:Mycobacterium bovis / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D050130:Oncolytic Virotherapy
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines