Action of recombinant alpha interferon against experimental and spontaneous metastases in a murine model.
The therapeutic potential of rHuIFN-alpha A/D, a hybrid human IFN molecule with equal activity on murine cells, was studied in experimental and spontaneous metastatic models of a murine colon carcinoma COLON 26. rHuIFN-alpha A/D inhibited experimental pulmonary metastases of COLON 26 and prolonged the survival of BALB/c mice. Dose scheduling, survival and tumour-cell clearance studies showed that the first 5 days were critical in the inhibition of pulmonary metastases. However, it is unlikely that lung NK cells were involved in the anti-metastatic effect of rHuIFN-alpha A/D because inhibition of pulmonary metastases and a decrease in radio-labelled tumour-cell survival was seen in BALB/c mice depleted selectively of their NK cells by prior treatment with rabbit antiasialoGMI serum. Although rHuIFN-alpha A/D stimulated NK-cell activity in BALB/c mice, it was ineffective in abrogating the NK suppressant action of rabbit anti-asialoGMI serum on murine lung NK cells. Thus, IFN may mediate its early antimetastatic effect via a mechanism independent of NK-cell stimulation. IFN also inhibited the development of lung metastases from s.c. COLON 26 tumors in normal, NK-depleted and T-cell-deficient mice.
Ramani
P
P
Imperial Cancer Research Fund, London, UK.
Balkwill
F R
FR
D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D007370:Interferon Type I / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000032:analysis; D008168:Lung / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D011994:Recombinant Proteins
D007370:Interferon Type I; D011994:Recombinant Proteins