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Synergistic effect of a granulocyte-macrophage colony-stimulating factor-transduced tumor vaccine and systemic interleukin-2 in the treatment of murine colorectal cancer hepatic metastases.
Ajay Jain; Jill E Slansky; Laurel C Matey; Heather E Allen; Drew M Pardoll; Richard D Schulick (Profiled Author: Ajay Jain)
Department of Surgery, Division of Immunology and Hematapoiesis, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Annals of surgical oncology 2003;10(7):810-20.
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-gamma 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.
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