Basic studies of IL-2 gene therapy for head and neck cancer

Transduction of the human interleukin-2 gene into tumor cells was carried out in order todevelop a new immunotherapy for advanced head and neck carcinomas with poor outcome. We transducedthe IL-2 gene into KB cells, a head and neck squamous cell carcinoma cell lineusing defective herpes simplex viral (HSV) amplicon vector as a gene transfer vehicle. a high levelIL-2 was secreted by IL-2 gene-transduced KB cells (KB/IL-2). The IL-2产品irradiated KB/IL-2 cells有时也作为非irradiated cells. In the tumorestablishment model in nude mice. IL-2 and interferon-γ (IFN-γ) at high concentrations were detectedin the sera of mice transplanted with KB/IL-2 cells. the spleen cells of nude mice transplantedwith KB/IL-2 cells exhibited high cytotoxic activity，compared to those from mice transplanted with KB cells and from untreated mice. Three of five micetransplanted with KB/IL-2 cells rejected tumors. In treatment of established tumors，therapeutic effects due to irradiated KB/IL-2 were dose-dependent. The suppressive effects on tumorgrowth were blocked by anti-asialo GM1anti-human IL-2 and anti-IFN-γ antibodies. Immunohistochemical observation revealed the presence ofasialo GM1 - 1 - 1 cells among the KB/IL-2 cells in tumors transplanted into nude mice.furthermore,combination treatment of IL-2 gene therapy and exogenous murine IL-12 administration showed asynergistic anti-tumor effect. Based on these resultsIL-2 gene therapy with or without IL-12 will be one of treatment strategies for advanced head andneck cancer cases with poor outcome。

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 poor outcome. We transduced the IL-2 gene into KB cells, a head and neck squamous cell carcinoma cell line, using 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-γ (IFN-γ) 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 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-γ antibodies. Immunohistochemical observation revealed the presence of asialo GM1ィイD1+ィエD1 cells among the KB/IL-2 cells in tumors transplanted into nude mice. Furthermore, the combination treatment of IL-2 gene therapy and exogenous murine IL-12 administration showed a synergistic anti-tumor effect. Based on these results, IL-2 gene therapy with or without IL-12 will be one of treatment strategies for advanced head and neck cancer cases with poor outcome.