Interferon‐activated tumor inhibition in vivo. Small amounts of interferon‐gamma inhibit tumor growth by eliciting host systemic immunoreactivity

Abstract

Ten international units (IU) of recombinant (r) or natural (n) murine interferon (MulFN)-gamma were used for the in vivo immunotherapy of a chemically induced fibrosarcoma (CE-2) of BALB/c mice. In vitro, doses of r-IFN-gamma below 100 units have a marginal antiproliferative effect on CE-2 cells and do not induce expression of H-2^d class-II antigens, whereas they do increase that of class-I antigens. In vivo, 10 daily injections of 10 IU of r- or n-MulFN-gamma at the challenge site provide significant protection against increasing doses of CE-2 tumor cells. This protection was enhanced when non-reactive T-lymphocytes from CE-2 tumor-bearing mice were admixed at a 10:1 ratio with the CE-2 tumor cells. Combined lymphocyte and r-MulFN-gamma treatment also inhibited the growth of already established tumors when it was started before these reached a mean diameter of 5 mm. Tumor inhibition depends upon activation of the host immune system. The antitumor activity of r-MulFN-gamma and T-lymphocytes was null when mice were first irradiated with 450 rads. Moreover, host leukocytes massively infiltrated the area of tumor growth and the small r-MulFN-gamma doses injected daily activated various host immunoreactivity mechanisms.