Genetically engineered tumor cell vaccine in a head and neck cancer model.
OBJECTIVE
Using a murine model, a novel tumor vaccine for head and neck squamous cell carcinoma expressing the granulocyte-macrophage colony stimulating factor (GM-CSF) gene was evaluated for its ability to protect against tumor challenge.


METHODS
Mice vaccinated in the floor of the mouth with the GM-CSF tumor cell vaccine were challenged with parental tumor cells, and subsequent tumor development was monitored. Specificity of the antitumor response was demonstrated by vaccinating the mice and then challenging them with an unrelated but syngeneic radiation-induced fibrosarcoma tumor cell line, RIF. Irradiated (only) tumor cells were used as a control to see whether an augmented antitumor response was attributable to possible increased immunogenicity that could theoretically be induced by the irradiation.


METHODS
The GM-CSF gene was transduced into tumor cells via a retroviral vector. The tumor cells were irradiated to prevent replication in vivo. GM-CSF concentrations were determined using ELISA, and physiological activity was confirmed using a biological assay with a GM-CSF-dependent cell line.


RESULTS
Vaccination with genetically engineered tumor cells significantly protected against subsequent tumor challenge (5% level) when compared to control groups. Mice were not protected when vaccinated and challenged with the unrelated tumor cell line, RIF. Mice vaccinated with irradiated (only) tumor cells were not protected, either.


CONCLUSIONS
Vaccination with genetically engineered tumor cells offers significant protection from later tumor challenge. The response is systemic and tumor specific, not due to an inflammatory response. Irradiation of the tumor cells does not account for the augmented antitumor response. This work supports the continued investigation of the GM-CSF tumor vaccine for the treatment of head and neck squamous cell carcinoma.
Couch
Marion
M
Department of Otolaryngology-Head and Neck Surgery, Outpatient Center, Johns Hopkins Hospital, Room 624, 601 North Caroline Street, Baltimore, MD 21287-0901, USA. mcouch@jhmi.edu
Saunders
John K
JK
O'Malley
Bert W
BW
Pardoll
Drew
D
Jaffee
Elizabeth
E
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005818:Genetic Engineering / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D014161:Transduction, Genetic / Q000379:methods; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor