Synergy between dendritic cells and GM-CSF-secreting tumor cells for the treatment of a murine renal cell carcinoma.
Dendritic cell (DC) immunotherapy for cancer certainly holds promises but definitely needs improvements, especially for enhancing tumor-specific responses able to eradicate preexisting tumors. To this end, we investigated here, for the treatment of a preimplanted murine renal cell carcinoma Renca, a new vaccination approach combining injection of DC and granulocyte macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cells. When treatment by either DC or Renca-mGM-CSF cells alone had no therapeutic effect at all, combined vaccines induced therapeutic response in 50% of the tumor-bearing mice, in a GM-CSF dose-dependent manner. Importantly, all these cured mice were protected against a rechallenge with parental Renca cells, indicating the generation of memory immune response. The combined vaccines induced elevated cytotoxic responses in all the cured mice and half of the uncured ones and a stronger systemic CD4+ T-cell-mediated interferon-gamma production in the cured vaccinated mice as compared with uncured ones. In conclusion, vaccines associating DC and GM-CSF-secreting tumor cells induce high therapeutic effect in mice with preexisting renal cell carcinoma that are correlated to the induction of specific CD8 and CD4+ T-cell responses. This original vaccination approach should be further evaluated in a clinical trial for the treatment of metastatic human renal cell carcinoma.
Driessens
Gregory
G
Faculty of Medicine, Laboratory of Cytology and Experimental Cancerology, Université Libre de Bruxelles, Brussels, Belgium.
Hoffmann
Paul
P
Pouwels
Michael
M
Zlotta
Alexandre
A
Schulman
Claude
C
Velu
Thierry
T
Bruyns
Catherine A
CA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007680:Kidney Neoplasms / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D014161:Transduction, Genetic
D019496:Cancer Vaccines; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor