Enhanced survival of IFN-alpha augmented IL-2 therapy of pulmonary metastases: efficacy comparable to interleukin-2 and lymphokine activated killer cells.
Recently, we reported enhanced tumor reduction using recombinant interferon-alpha A/D (IFN) combined with interleukin-2 (IL-2). Similar synergism affecting survival was assessed in treatment of both early and advanced pulmonary metastases. This combination was compared with the current "standard" IL-2 and lymphokine activated killer (LAK) therapy in the treatment of early and advanced pulmonary metastases. C57BL/6 mice injected via tail vein with the weakly immunogenic methylcholanthrene-induced murine fibrosarcoma MCA-106 were treated intraperitoneally with IL-2 (50,000 units b.i.d.), IFN (50,000 units q.d.), LAK (2.5-10 x 10(7)), or various combinations of above. Treatment of both early Day 3 and advanced Day 10 metastases using IL-2/IFN reduced metastases and prolonged survival over both controls and IL-2 alone. It was superior to IFN, LAK, and IFN/LAK. Addition of LAK to IL-2/IFN demonstrated no added benefit. Although no mortality was observed during treatment of Day 3 metastases, treatment of Day 10 advanced pulmonary metastases for 9 days with IL-2/IFN resulted in early deaths (33%) without visible tumor, indicating possible toxicity of treatment. These results show survival benefit of IL-2/IFN over IL-2, IFN, or LAK treatment in the therapy of early and advanced pulmonary metastases, albeit with added toxicity. Its relative simplicity and comparable efficacy to the more complex and costly IL-2/LAK provide important advantages for potential clinical applications.
Kim
B
B
Department of Surgery, University of Utah, Salt Lake City 84132.
Warnaka
P
P
D000818:Animals; D004357:Drug Synergism; D005260:Female; D016219:Immunotherapy, Adoptive; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins
D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins