Induction of antibody response to human tumor antigens by gene therapy using a fusigenic viral liposome vaccine.
Development of effective cancer vaccines would help prevent and control tumor progression. A novel approach of immunizing against tumor antigens is in vivo gene vaccination. We have developed a fusigenic viral liposome vector using HVJ (hemagglutinating virus of Japan) and liposome to deliver human tumor antigen genes effectively to cells in vivo. Plasmids containing the human tumor antigen genes MAGE-1 and MAGE-3 were encapsulated in fusigenic viral liposomes and injected into mice intramuscularly. MAGE-1 and -3 recombinant proteins were used in Western blotting and affinity ELISA for assessment of antibody responses. Mice immunized with MAGE-1 and -3 gene vaccine individually were shown to produce anti-MAGE-1 and -3 IgG antibody responses respectively. Animals immunized with plasmid alone did not induce anti-MAGE-1 or -3 IgG responses. Antibody responses could be enhanced on reimmunization with the gene vaccines. Muscle biopsies taken after vaccine injection were verified to express gene-specific mRNA transcripts. Mice immunized with MAGE-1 or -3 gene vaccines were shown to induce antibodies that could cross-react with the respective recombinant proteins. This study demonstrates that in vivo immunization using HVJ-liposome containing human tumor antigen genes can effectively deliver and induce immune responses to the respective whole proteins.
Okamoto
T
T
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica 90404, USA.
Kaneda
Y
Y
Yuzuki
D
D
Huang
S K
SK
Chi
D D
DD
Hoon
D S
DS
D000818:Animals; D000912:Antibodies, Neoplasm; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D015153:Blotting, Western; D019496:Cancer Vaccines; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes; D008297:Male; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D018108:Respirovirus
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D008081:Liposomes; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; C489518:Mageb1 protein, mouse; C489519:Mageb3 protein, mouse; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins