Enhanced in vivo therapy of pulmonary metastases with interferon and interleukin-2.
Interleukin-2 (IL-2) can mediate in vivo tumor regression at high doses. To enhance this efficacy, we studied the effect of adding a human hybrid recombinant interferon alpha A/D (rHuIFN-alpha-A/D) because of its known in vitro augmentation of immune-mediated tumoricidal activity. C56BL/6 mice bearing established pulmonary metastases induced by the iv injection of the methylcholanthrene-induced fibrosarcoma MCA 106 were treated for 12 days with intraperitoneal injections of (1) Hanks' balanced salt solution, (2) recombinant IL-2, (3) rHuIFN-alpha-A/D, and (4) a combination of IL-2 and HuIFN-alpha-A/D. IL-2 and interferon each had some antitumor activity. However, maximal reduction of pulmonary metastases consistently resulted from combining IL-2 with interferon. In two of four experiments, this combination was significantly better compared to either IL-2 or interferon treatment alone. The most potent regimen was 12 days of IL-2 (50,000 units bid) together with rHuIFN-alpha-A/D (50,000 units ip qd). No consistent pattern of proliferative or cytotoxic activity was found against a panel of stimulator and target cells. These results demonstrate enhanced antitumor efficacy of combining recombinant interferon alpha and IL-2 against established pulmonary metastases. Potential clinical applications are suggested by these data.
Kim
B
B
Department of Surgery, Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Ohio 44109.
Stein
S
S
Warnaka
P
P
Franceschi
D
D
D000818:Animals; D002455:Cell Division; D004357:Drug Synergism; D007372:Interferons / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D007376:Interleukin-2; D007372:Interferons