Therapeutic efficiency of IL-2 gene transduced tumor vaccine for head and neck carcinoma.
Transduction of the human interleukin-2 (IL-2) gene into tumor cells was carried out in order to develop a new immunotherapy for advanced head and neck carcinomas with a poor outcome. We transduced the IL-2 gene into KB cells, a head and neck squamous cell carcinoma cell line, using a defective herpes simplex viral (HSV) amplicon vector as a gene transfer vehicle. A high level of IL-2 was secreted by IL-2 gene-transduced KB cells (KB/IL-2). The IL-2 producibility of irradiated KB/IL-2 cells was almost the same as that of non-irradiated cells. In the tumor establishment model in nude mice, IL-2 and interferon-gamma (IFN-gamma) at high concentrations were detected in the sera of mice transplanted with KB/IL-2 cells. The spleen cells of nude mice transplanted with KB/IL-2 cells exhibited high cytotoxic activity compared to those from mice transplanted with KB cells and from untreated mice. Three of five mice transplanted with KB/IL-2 cells rejected tumors. In the treatment of established tumors, therapeutic effects due to irradiated KB/IL-2 were dose-dependent. The suppressive effects on tumor growth were blocked by anti-asialo GM1, anti-human IL-2 and anti-IFN-gamma antibodies. Immunohistochemical observation revealed the presence of asialo GM1(+) cells among the KB/IL-2 cells in tumors transplanted into nude mice.
Mizuno
H
H
Department of Otolaryngology, Yokohama City University School of Medicine, 3-9 Fukuura Kanazawa-ku, Yokohama, Japan. m_163@med.yokohama-cu.ac.jp
Yanoma
S
S
Nishimura
G
G
Hattori
S
S
Ito
T
T
Okudera
K
K
Tsukuda
M
M
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002522:Chlorocebus aethiops; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010957:Plasmids; D018139:Simplexvirus / Q000378:metabolism; D013154:Spleen / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D019496:Cancer Vaccines; D007376:Interleukin-2; D007371:Interferon-gamma