Interferon-activated tumor inhibition in vivo. Small amounts of interferon-gamma inhibit tumor growth by eliciting host systemic immunoreactivity.
Ten international units (IU) of recombinant (r) or natural (n) murine interferon (MuIFN)-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-2d class-II antigens, whereas they do increase that of class-I antigens. In vivo, 10 daily injections of 10 IU of r- or n-MuIFN-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-MuIFN-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-MuIFN-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-MuIFN-gamma doses injected daily activated various host immunoreactivity mechanisms.
Giovarelli
M
M
Cofano
F
F
Vecchi
A
A
Forni
M
M
Landolfo
S
S
Forni
G
G
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D014316:Tritium; D007371:Interferon-gamma; D013936:Thymidine