Anti-tumor immunity against CT26 colon tumor in mice immunized with plasmid DNA encoding beta-galactosidase fused to an envelope protein of endogenous retrovirus.
Endogenous retroviral gene products have been recognized as being expressed in human cancerous tissues. However, these products have not been shown to be antigenic targets for T-cells, possibly due to immune tolerance. Since carcinogen-induced colon tumor CT26 expresses an envelope protein, gp70, of an endogenous ecotropic murine leukemia virus that is comparable to human tumor-associated antigens, we examined whether a DNA vaccine containing the gp70 gene induces protective immunity against CT26 cells. Injection of mice with plasmid DNA (pDNA) encoding gp70 alone failed to induce anti-gp70 antibody (Ab) or anti-CT26 cytotoxic T lymphocyte (CTL) responses. However, immunization with pDNA encoding the beta-galactosidase (beta-gal)/gp70 fusion protein induced anti-gp70 Ab and anti-CT26 CTL responses and conferred protective immunity against CT26 cells. These results indicate that beta-gal acts as an immunogenic carrier protein that helps in the induction of immune responses against the poorly immunogenic gp70. Considering these results, it is possible that potential tolerance to the endogenous retroviral gene products expressed by human tumors may be overcome by DNA vaccines that contain an endogenous retroviral gene fused to genes encoding immunogenic carrier proteins.
Takeda
J
J
Department of Internal Medicine II, Fukushina Medical University School of Medicine, Fukushima 960-1295, Japan. j-takeda@fmu.ac.jp
Sato
Y
Y
Kiyosawa
H
H
Mori
T
T
Yokoya
S
S
Irisawa
A
A
Miyata
M
M
Obara
K
K
Fujita
T
T
Suzuki
T
T
Kasukawa
R
R
Wanaka
A
A
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000401:mortality / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D005260:Female; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009363:Neoplasm Proteins / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D001616:beta-Galactosidase