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

Research output: Contribution to journalArticlepeer-review

Abstract

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-γ 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.

Original languageEnglish (US)
Pages (from-to)810-820
Number of pages11
JournalAnnals of surgical oncology
Volume10
Issue number7
DOIs
StatePublished - 2003

Keywords

  • Colorectal
  • GM-CSF
  • IL-2
  • Metastases
  • Tumor vaccine

ASJC Scopus subject areas

  • Surgery
  • Oncology

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