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Treament of liver metastases from colon carcinoma with autologous tumor vaccine expressing granulocyte‐macrophage colony‐stimulating factor
Author(s) -
Suh Kwang Wook,
Piantadosi Steven,
Yazdi Hamid A.,
Pardoll Drew M.,
Brem Henry,
Choti Michael A.
Publication year - 1999
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/(sici)1096-9098(199912)72:4<218::aid-jso7>3.0.co;2-n
Subject(s) - medicine , colorectal cancer , granulocyte macrophage colony stimulating factor , metastasis , immunotherapy , colon carcinoma , cancer research , immunology , vaccination , cancer , immune system , oncology , cytokine
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. J. Surg. Oncol. 1999;72:218–224. © 1999 Wiley‐Liss, Inc.