Basic studies on IL-2 gene therapy for head and neck carcinoma

Abstract

Basic studies on transduction of the interleukin-2 (IL-2) gene into tumor cells were carried out in order to develop a new immunotherapy for head and neck carcinomas. We transduced the IL-2 gene into KB cells using defective herpes simplex viral (HSV) amplicon vector as the gene transfer vehicle. A high level of IL-2 was produced by IL-2 gene transduced KB cells (KB/IL-2). Human peripheral blood mononuclear cells (PBMC) cultured in medium containing the culture supernatant of KB/IL-2 cells showed stronger cytotoxic activity against KB cells than the control. In in vivo studies, high levels of IL-2 and interferon-gamma (IFN-gamma) were detected in the serum of nude mice transplanted with KB/IL-2 cells. The spleen cells of KB/IL-2 cell-transplanted nude mice exhibited high cytotoxic activity. Three of 5 nude mice transplanted with KB/IL-2 cells were completely cured of their tumor, and all 3 mice survived for over 120 days. All 5 nude mice transplanted with KB/lacZ cells, and all 5 nude mice transplanted with KB cells died within 120 days as a result of tumor progression. In conclusion, transduction of IL-2 gene tumor cells was corroborated by the high level of IL-2 produced by KB/IL-2 cells. The mechanisms of tumor rejection on KB/IL-2 transplanted nude mice were thought to be that effector cells stimulated by IL-2 derived from transplanted KB/IL-2 cells killed tumor cells, and IFN-gamma produced by activated NK cells showed a synergistic effect on tumor cells-killing.