Effects of IL-12 on human ovarian tumors engrafted into SCID mice

Objective. The effects oi:murine interleuken (IL)-12 on the growth of surgi cal specimen-derived malignant human ovarian tumors engrafted in severe com bined immunodeficient (SCID) mice were, assessed. The SCID mouse model faci litated the evaluation IL-12's effect on the host innate immune response ag ainst human ovarian cancer xenografts. Methods. Equal portions of specimen-derived human ovarian carcinoma were en grafted subcutaneously into SCID mice. After 7 days, mice were, placed into one of two treatment: groups: (1) placebo/control or (2) murine IL-12 (0.3 3 mcg/day intraperitoneally x 20 days). Anti-asialo GM1 was administered on day 0 to 3 mice from the IL-12-treated group. Serial tumor volumes were me asured, On day 21, mice from each group were sacrificed, and tumors and spl eens were evaluated. Data analysis included chi(2) tests, Student t tests, and analysis of variance when appropriate. The entire experiment was repeat ed for a total of three times with similar results. A total of 45 mice and two different human tumor specimens were, utilized, Representative data wer e reported. Results. IL-12 resulted in mean tumor growth delay and regression when comp ared to controls (P = 0.02). Among the IL-12 group, 22% (2/9) developed com plete remissions. When anti-asialo GM1 was added prior to IL-12, no tumor g rowth delay was noted. Splenic weights were higher among IL-12-treated mice compared to controls (P < 0.01). Spleen sections demonstrated expanded whi te pulp among IL-12-treated mice compared to controls. Histologic evaluatio n of tumor sections revealed central necrosis among tumors from mice treate d with IL-12. Immunohistochemical stains identified increased numbers of NK cells in clusters within tumors from mice treated with IL-12 whereas NK ce lls were found to be sparsely scattered in control tumors. Conclusions. Murine IL-12 treatment resulted in significant tumor growth de lay and tumor regression in SCID mice engrafted with human ovarian cancer. The data support an immunologic basis for the observed anti-tumor effects a nd suggest a role for NK cells as part of the effector pool. The current da ta support the clinical evaluation of IL-12 in the treatment of epithelial ovarian cancer. (C) 1999 Academic Press.