Therapeutic potential of tumor necrosis factor-alpha and gamma-interferon in experimental human ovarian cancer.

We have studied the activity of recombinant human gamma-interferon and recombinant human tumor necrosis factor alpha against four human ovarian cancer i.p. xenografts OS, LA, HN, and DO derived from primary tumor material. In the OS xenograft all control mice died by 42 days and therapy starting 7 days after tumor cell injection with 5 X 10(4) units recombinant human gamma-interferon or 1 microgram recombinant human tumor necrosis factor alpha alone had no significant effect on cumulative survival in three separate experiments. However, a combination of the two agents resulted in 85% cumulative survival at 150 days. This combination therapy also significantly increased survival of mice treated as late as 21 days after tumor cell injection. In the LA xenograft (where control mice were all dead by 23 days) therapy with either agent alone, or a combination, more than doubled survival time of mice. In the HN xenograft all control mice were dead at 22 days whereas either therapy alone or in combination gave +85% cumulative survival at 100 days. In a fourth xenograft, DO, survival of mice in the combination therapy group was significantly increased. Thus these two biological therapies, alone or in combination, show significant activity against human ovarian cancer cells.