Distinct antitumor mechanisms of recombinant murine interferon-gamma against two murine tumor models

The antitumor activity of recombinant murine interferon-gamma (rMuIFN-gamma) against B16 melanoma and EL4 thymoma, which display different sensitivities in in vitro tests, was studied. In antiproliferation tests, B16 cells were highly sensitive to rMuIFN-gamma and growth was markedly inhibited at as low as 10 U/ml, whereas EL4 cells resisted treatment even at concentration as high as 10(4) U/ml. One of these two tumors was inoculated i.d. into C57BL/6 mice and then rMuIFN-gamma (10(4) units) was repeatedly injected s.c. starting 1 day after the tumor inoculation. For the B16-bearing mice, tumor growth was markedly suppressed and the mean survival period was prolonged, but cured mice were not observed. For mice bearing EL4 cells, the therapeutic effects were more pronounced and cured mice were observed. The EL4-cured mice showed in vivo protective immunity against EL4 tumors but not against P815 tumors, indicating tumor specificity. Histologically, a large number of lymphocytes had infiltrated the necrotic tumor mass. These results indicated that rMuIFN-gamma may have not only a direct effect but also an indirect effect in host-mediated murine response on the growth of murine tumor cells under in vivo conditions.