Synergistic Effect of a Granulocyte-macrophage Colony-stimulating Factor-transduced Tumor Vaccine and Systemic Interleukin-2 in the Treatment of Murine Colorectal Cancer Hepatic Metastases

Background: Granulocyte-macrophage colony-stimulating factor-transduced tumor cell vaccines are less effective against cancer as the interval between metastasis and the initial vaccination increases.

Methods: Hepatic metastases were generated in BALB/c mice by using a syngeneic colorectal cancer line (CT26) with a splenic injection model. Irradiated CT26 cells transduced to secrete granulocyte-macrophage colony-stimulating factor were used as vaccine. Treatment groups received vaccine, systemic interleukin (IL-2), or both. Livers were examined for gross metastases 21 days after tumor challenge. Splenocytes were analyzed for in vitro activity against CT26 by using an enzyme-linked immunospot assay and a cytotoxic T lymphocyte assay.

Results: Eighty-eight percent of mice treated with vaccines and IL-2 were tumor free on day 21 (P </=.001 vs. control). Treatment with vaccines or IL-2 alone did not result in a significant treatment effect. Splenocytes from mice treated with both vaccines and IL-2 showed greater CT26 lysis than splenocytes from mice treated with vaccines alone at effector:target ratios of 100, 30, and 10 (P <.05 for all). More splenocytes from these mice released interferon-gamma in response to stimulation with the CT26 tumor antigen AH1 compared with mice treated with vaccines alone (P =.05).

Conclusions: Systemic IL-2 augments tumor vaccine efficacy in the treatment of microscopic murine colorectal hepatic metastases.