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From the Departments of Surgery (AJ, HEA, RDS), Oncology (LCM, DMP), and Medicine (DMP), Division of Immunology and Hematapoiesis, Johns Hopkins University School of Medicine, Baltimore, Maryland; and the Department of Immunology (JES), University of Colorado Health Sciences Center, Denver, Colorado.
Correspondence: Address correspondence and reprint requests to: Richard D. Schulick, MD, the Johns Hopkins Hospital, 600 North Wolfe Street, Blalock 657, Baltimore, MD 21287; Fax: 410-614-9880; E-mail: rschulick{at}jhmi.edu
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-
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.
Key Words: GM-CSF • IL-2 • Tumor vaccine • Colorectal • Metastases
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