Induction of antibody response to human tumor antigens by gene therapy using a fusigenic viral liposome vaccine

Abstract

Development of effective cancer vaccines would help pre-MAGE-1 and -3 IgG antibody responses, respectively. Anivent and control tumor progression. A novel approach of mals immunized with plasmid alone did not induce antiimmunizing against tumor antigens is in vivo gene vacci-MAGE-1 or -3 IgG responses. Antibody responses could nation. We have developed a fusigenic viral liposome vecbe enhanced on reimmunization with the gene vaccines. tor using HVJ (hemagglutinating virus of Japan) and lipoMuscle biopsies taken after vaccine injection were verified some to deliver human tumor antigen genes effectively to to express gene-specific mRNA transcripts. Mice immuncells in vivo. Plasmids containing the human tumor antigen ized with MAGE-1 or -3 gene vaccines were shown to genes MAGE-1 and MAGE-3 were encapsulated in fusiinduce antibodies that could cross-react with the respective genic viral liposomes and injected into mice intramusculrecombinant proteins. This study demonstrates that in vivo arly. MAGE-1 and -3 recombinant proteins were used in immunization using HVJ-liposome containing human Western blotting and affinity ELISA for assessment of antitumor antigen genes can effectively deliver and induce body responses. Mice immunized with MAGE-1 and -3 immune responses to the respective whole proteins. gene vaccine individually were shown to produce anti-

Induction of melanoma-associated antigen systemic immunity upon intratumoral delivery of interferon-γ retroviral vector in melanoma patients

“…Previously, we have shown that anti-MAGE-A3 Ab will cross-react with MAGE-A1 protein. 10 Therefore, if the melanoma lesion expresses a MAGE-A protein with significant homology to MAGE-A1, it has a significant potential to produce a crossreacting immune response.…”

“…These modalities include delivery to tumor cells, vaccination with tumorassociated antigen(s) (Ags), and delivery of specific cytokine(s) for immunomodulation or modulation of tumor cell growth and properties. [7][8][9][10][11] The delivery of cytostatic cytokines such as interferon-␥ (IFN-␥) has shown promising results in animal and human studies. IFN-␥ is a type II IFN, whereas IFN-␣ and IFN-␤ are type I.…”

Protective immunization against melanoma by gp100 DNA–HVJ-liposome vaccine

“…11 Recently, we demonstrated that repetitive gene transfer can be achieved by HVJ-liposome vector system without side-effects or neutralization of the delivery system. 12 In our previous studies we demonstrated that when pcDNA3 plasmid containing the human tumor antigen genes MAGE-1 and MAGE-3 were encapsulated in HVJ-liposomes and injected into mice intramuscularly, there were no side-effects and there was highly efficient transfection of muscle cells for several weeks.…”

“…12 In our previous studies we demonstrated that when pcDNA3 plasmid containing the human tumor antigen genes MAGE-1 and MAGE-3 were encapsulated in HVJ-liposomes and injected into mice intramuscularly, there were no side-effects and there was highly efficient transfection of muscle cells for several weeks. 11 Recently, we improved the HVJ-liposome system for more efficient gene delivery by changing the lipid components of the liposomes, and developed a novel HVJ-AVE (artificial viral envelope) liposome which increased gene expression in mouse skeletal muscle and liver five to 10 times higher compared with conventional HVJliposomes. 13 In this study, we assessed the fusigenic HVJ-liposome system to transfer the gene encoding human gp100 antigen into mice intramuscularly.…”

Novel immunotherapy for peritoneal dissemination of murine colon cancer with macrophage inflammatory protein-1β mediated by a tumor-specific vector, HVJ cationic liposomes

“…The hemagglutinating virus of Japan ( HVJ ) -liposome gene transfer method enables delivery of nucleic acids or proteins directly and efficiently into host cells in vivo by means of the virus' cell fusion machinery. 19 We have developed many types of liposomes with the HVJ envelope and found that HVJ anionic liposomes were effective for transfer of genes to solid organs such as liver and muscle, whereas HVJ cationic liposomes were preferable for gene transfer to surface areas of organs such as bronchial epithelium and biliary epithelium. 20 -22 Cationic liposomes appeared to be more effective for cancer gene therapy than the anionic type.…”