INDUCTION OF ANTITUMOR IMMUNITY AND TREATMENT OF PREESTABLISHED TUMORBY INTERLEUKIN-6-GENE TRANSFECTED MELANOMA-CELLS COMBINED WITH LOW-DOSE INTERLEUKIN-2

Transfer of cytokine genes into tumor cells has proven a valuable appr oach for cancer treatment. In order to generate a more effective cance r vaccine, we transfected the human interleukin-6 (IL-6) gene into B16 melanoma cells. A B16 cell clone secreting the highest level of IL-6 was obtained by G418-resistant selection, limiting dilution and IL-6 a ssay. The IL-6-gene-transfected tumor cells exhibited in vitro growth inhibition, reduced tumorigenicity and decreased metastatic competence . After immunization with the inactivated IL-6-gene-transfected vaccin e, the murine cytotoxic T lymphocyte activity, natural killer activity and lymphokine-activated killer activity increased markedly. After tr eatment with the vaccine, the tumor-bearing mice showed significant gr owth inhibition of subcutaneous tumor, reduction in pulmonary metastas es and extension of survival time. The above therapeutic effect was be tter when low-dose IL-2 was administered simultaneously, although this dosage of IL-2 had no in vivo antitumor effect. These data demonstrat ed that IL-6-gene-transfected cancer vaccine has a potent antitumor ef fect via efficient induction of antitumor immunity, and a better thera peutic effect could be achieved when the vaccine is combined with low- dose IL-2 as adjuvant.