title: Adenoviral transfer of xenogeneic MHC class I gene results in loss of tumorigenicity and inhibition of tumor growth.
abstract: The immune system confers protection against a variety of pathogens and contributes to the destruction of neoplastic cells. Foreign major histocompatibility complex (MHC) protein serves as a potent stimulus to the immune system. In this report, a mouse H-2Kb gene was introduced into two poorly immunogenic tumor cell lines, a mouse colonic carcinoma cell line, MCA-26 (H-2Kd), and a rat mammalian carcinoma cell line, LN-4, in an effort to stimulate tumor rejection. Our results showed that the expression of xenogeneic MHC class I antigen completely abolished the LN-4 tumorigenicity in rats, whereas the expression of allogeneic MHC class I antigen only partially reduced the MCA-26 tumorigenicity in mice. Rats with tumor regression of LN-4/H-2Kb developed a T helper type 1-dominant response, whereas rats with LN-4 tumor growth developed a T helper type 2-dominant response. The immunized rats that experienced LN-4/H-2Kb tumor regression further developed protective immunity against a subsequent challenge of LN-4 cells. This protective immunity was mediated by the LN-4 tumor-specific cellular immune response against both the transduced and the parental LN-4 cells. Recombinant adenoviral vectors are highly efficient at in vitro and in vivo gene delivery. The LN4 cells transfected with the recombinant adenovirus AdV-H-2Kb in vitro expressed the cell surface H-2Kb molecule by fluorescence-activated cell sorter analysis. Adenovirus-mediated H-2Kb gene transfer in vivo can further significantly inhibit pre-established LN-4 tumors. Those rats with complete tumor regression further developed protective immunity against the subsequent challenge of a parental LN-4 tumor. Therefore, our study indicates that the adenovirus-mediated transfer of xenogeneic MHC class I gene may be an effective alternative to the current protocol of cancer gene therapy in which the allogeneic MHC class I gene is used.
authors.affiliation: Department of Microbiology, College of Medicine, Saskatoon Cancer Center, University of Saskatchewan, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Campbell
authors.forename: T
authors.initials: T
authors.lastname: Moyana
authors.forename: S
authors.initials: S
authors.lastname: Carlsen
authors.forename: C
authors.initials: C
authors.lastname: Zheng
authors.forename: J
authors.initials: J
authors.lastname: Xiang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006183:H-2 Antigens / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse