Synergistic effect of a granulocyte-macrophage colony-stimulating factor–transduced tumor vaccine and systemic interleukin-2 in the treatment of murine colorectal …

A Jain, JE Slansky, LC Matey, HE Allen… - Annals of surgical …, 2003 - Springer
A Jain, JE Slansky, LC Matey, HE Allen, DM Pardoll, RD Schulick
Annals of surgical oncology, 2003Springer
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 …
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.
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