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

Abstract

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. 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. 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. 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.