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

Abstract

Objective: The effects of murine interleuken (IL)-12 on the growth of surgical specimen-derived malignant human ovarian tumors engrafted in severe combined immunodeficient (SCID) mice were assessed. The SCID mouse model facilitated the evaluation IL-12's effect on the host innate immune response against human ovarian cancer xenografts.

Methods: Equal portions of specimen-derived human ovarian carcinoma were engrafted subcutaneously into SCID mice. After 7 days, mice were placed into one of two treatment groups: (1) placebo/control or (2) murine IL-12 (0.33 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 measured. On day 21, mice from each group were sacrificed, and tumors and spleens were evaluated. Data analysis included chi2 tests, Student t tests, and analysis of variance when appropriate. The entire experiment was repeated for a total of three times with similar results. A total of 45 mice and two different human tumor specimens were utilized. Representative data were reported.

Results: IL-12 resulted in mean tumor growth delay and regression when compared to controls (P = 0. 02). Among the IL-12 group, 22% (2/9) developed complete remissions. When anti-asialo GM1 was added prior to IL-12, no tumor growth delay was noted. Splenic weights were higher among IL-12-treated mice compared to controls (P < 0.01). Spleen sections demonstrated expanded white pulp among IL-12-treated mice compared to controls. Histologic evaluation of tumor sections revealed central necrosis among tumors from mice treated with IL-12. Immunohistochemical stains identified increased numbers of NK cells in clusters within tumors from mice treated with IL-12 whereas NK cells were found to be sparsely scattered in control tumors.

Conclusions: Murine IL-12 treatment resulted in significant tumor growth delay and tumor regression in SCID mice engrafted with human ovarian cancer. The data support an immunologic basis for the observed anti-tumor effects and suggest a role for NK cells as part of the effector pool. The current data support the clinical evaluation of IL-12 in the treatment of epithelial ovarian cancer.