Novel immunotherapy for peritoneal dissemination of murine colon cancer with macrophage inflammatory protein-1beta mediated by a tumor-specific vector, HVJ cationic liposomes.
A critical issue for cancer treatment is control of metastatic or disseminated tumors. Although immune gene therapy has been considered as a possible strategy for treatment of such tumors, successful results have not yet been obtained. To evoke antitumor immunity more efficiently, macrophage inflammatory protein-1beta (MIP-1beta) was used for gene therapy of colon cancer in mice. Injection of hemagglutinating virus of Japan (HVJ) cationic liposomes-MIP-1beta into subcutaneous tumor masses resulted in local expression of MIP-1beta and local accumulation of CD4(+) T lymphocytes. Few studies of cancer gene therapies have targeted peritoneal dissemination. In a mouse model of peritoneal dissemination of colon tumor, we used a luciferase-based assay to demonstrate that HVJ cationic liposomes had high tumor specificity and were effective vectors for transfer of genes in peritoneal dissemination. When mice were treated by intraperitoneal injection of HVJ cationic liposomes containing the MIP-1beta gene, the survival periods of the MIP-1beta-treated mice were significantly longer than those of control mice. Therefore, this HVJ cationic liposome strategy may serve as a powerful tool against peritoneal disseminated cancer.
Miyata
T
T
Division of Gene Therapy Science, Osaka University School of Medicine, Suita, Osaka, Japan.
Yamamoto
S
S
Sakamoto
K
K
Morishita
R
R
Kaneda
Y
Y
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054407:Chemokine CCL4; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D007124:Immunoenzyme Techniques; D007167:Immunotherapy / Q000379:methods*; D008081:Liposomes; D019402:Macrophage Inflammatory Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D029082:Sendai virus / Q000235:genetics*; D014407:Tumor Cells, Cultured
D054407:Chemokine CCL4; D008081:Liposomes; D019402:Macrophage Inflammatory Proteins