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.
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.
Jain
Ajay
A
Department of Surgery, Division of Immunology and Hematapoiesis, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Slansky
Jill E
JE
Matey
Laurel C
LC
Allen
Heather E
HE
Pardoll
Drew M
DM
Schulick
Richard D
RD
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology*; D003601:Cytotoxicity Tests, Immunologic; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007376:Interleukin-2 / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D007376:Interleukin-2; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C082598:aldesleukin