Treatment of liver metastases from colon carcinoma with autologous tumor vaccine expressing granulocyte-macrophage colony-stimulating factor.
OBJECTIVE
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.
Suh
K W
KW
Department of Surgery, Ajou Univeristy School of Medicine, Suwon, Korea.
Piantadosi
S
S
Yazdi
H A
HA
Pardoll
D M
DM
Brem
H
H
Choti
M A
MA
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000473:pathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000276:immunology*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor