Treatment of liver metastases from colon carcinoma with autologous tumor vaccine expressing granulocyte-macrophage colony-stimulating factor.

BACKGROUND AND OBJECTIVES: In preclinical studies, tumor cells genetically altered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) can generate systemic antitumor immunity. Clinically relevant immunotherapeutic approaches for the treatment of colorectal cancer should address efficacy within the liver, a common site of metastatic disease. We investigated the effect of irradiated colon cancer cells engineered to produce GM-CSF on protecting from and treating established liver metastases.
METHODS: Using a model of liver metastasis by intrahepatic injection of CT-26 murine colon carcinoma cells in syngeneic BALB/c mice, GM-CSF-producing irradiated cells were given as an intradermal vaccine either 14 days prior to hepatic challenge or in animals with early established tumor (days 5 and 10). The presence of tumor, tumor volume, and survival were endpoint determinants.
RESULTS: Animals receiving GM-CSF-producing vaccination demonstrated significant protection from subsequent hepatic challenge of viable tumor cells, even at the highest challenge doses. In animals with early established tumors, a significant response was seen with prolongation in survival.
CONCLUSIONS: We conclude that GM-CSF autologous tumor vaccination was effective for the treatment of hepatic colorectal metastases in this murine model. These findings provide support for immunotherapeutic approaches for metastatic liver cancer. Copyright 1999 Wiley-Liss, Inc.