Induction of antitumor immunity and treatment of preestablished tumor by interleukin-6-gene-transfected melanoma cells combined with low-dose interleukin-2.
Transfer of cytokine genes into tumor cells has proven a valuable approach for cancer treatment. In order to generate a more effective cancer 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 assay. 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 vaccine, the murine cytotoxic T lymphocyte activity, natural killer activity and lymphokine-activated killer activity increased markedly. After treatment with the vaccine, the tumor-bearing mice showed significant growth inhibition of subcutaneous tumor, reduction in pulmonary metastases and extension of survival time. The above therapeutic effect was better when low-dose IL-2 was administered simultaneously, although this dosage of IL-2 had no in vivo antitumor effect. These data demonstrated that IL-6-gene-transfected cancer vaccine has a potent antitumor effect via efficient induction of antitumor immunity, and a better therapeutic effect could be achieved when the vaccine is combined with low-dose IL-2 as adjuvant.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D016233:Immunotherapy, Active; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014612:Vaccines / Q000235:genetics / Q000494:pharmacology
D007376:Interleukin-2; D015850:Interleukin-6; D014612:Vaccines