Immunotherapy of bladder cancer with cytokine gene-modified tumor vaccines.
This study explored the use of cytokine gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology and responds to treatment in a manner similar to that of its human counterpart. In a previous study we have shown that interleukin 2 (IL-2)-secreting, irradiated, MBT-2 cell preparations were capable of curing animals from orthotopically established tumors and engendered protective immunological memory in the cured animals. In this study we have compared the effectiveness of several cytokines and found that while IL-1 alpha, IL-1 beta, and gamma-interferon were only weakly effective in the therapeutic vaccination protocol, granulocyte-macrophage colony-stimulating factor was almost as effective as but not superior to IL-2, as reported previously for another tumor model system. Induction of cytotoxic T-lymphocyte correlated only poorly with the therapeutic benefit of the cytokine gene-modified tumor cell preparations, questioning its prognostic value for the development of improved genetically modified tumor vaccines.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
S
S
Saito
R
R
Bannerji
B
B
Gansbacher
F M
FM
Rosenthal
P
P
Romanenko
W D
WD
Heston
W R
WR
Fair
E
E
Gilboa
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*
D007375:Interleukin-1; D007376:Interleukin-2; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor