Efficacy of an osmotic pump delivered, GM-CSF-based tumor vaccine in the treatment of upper aerodigestive squamous cell carcinoma in rats.
OBJECTIVE
Upper aerodigestive tract (UADT) cancer has not experienced significant overall survival improvement for over 20 years, and no successful treatments for systemic disease exist. Most patients with UADT cancer experience immune suppression, therefore immune restorative therapies may offer promise for these patients. We presently tested the efficacy of granulocyte macrophage-colony stimulating factor (GM-CSF) delivered via 28-day continuous infusion pump, in combination with irradiated tumor cells, in a flank model of UADT cancer.


METHODS
Five groups of rats were inoculated with syngeneic mucosally derived squamous carcinoma cells (FAT-7). Osmotic minipumps were implanted in the contralateral flank to deliver GM-CSF at 0 (PBS), 0.1, 1, 10, or 100 ng/day (n = 6 per group) for 28 days; 10(6) irradiated FAT-7 cells (ITC) were injected at the site of the GM-CSF infusion on days 0, 3, 7, 14, and 21 immune infiltrates in tumors were analyzed.


RESULTS
Rats that received 10 or 100 ng/day GM-CSF/ITC had a significantly slower tumor growth rate compared to those who received 0, 0.1, or 1 ng/day (ANOVA, P < 0.01). There were increased CD 4+, CD 8+, and CD 68+ cells in tumors of GM-CSF/ITC treated animals over controls.


CONCLUSIONS
GM-CSF (10 or 100 ng/day) delivered locally via osmotic pump with ITC slows the growth rate of mucosally derived squamous cell carcinoma in rats while improving immune cell infiltrates. The efficacy of locally delivered GM-CSF immunotherapy in this model may be a first step toward this immunotherapy strategy for humans.
Djalilian
Hamid R
HR
Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA.
Caicedo
Emiro
E
Lessan
Khashayar
K
Grami
Vahid
V
Le
Chap T
CT
Spellman
Stephen R
SR
Pambuccian
Stephan
S
Hall
Walter A
WA
Low
Walter C
WC
Ondrey
Frank G
FG
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor / Q000528:radiation effects / Q000637:transplantation; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005240:Feasibility Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D016233:Immunotherapy, Active; D007213:Indomethacin / Q000627:therapeutic use; D015918:Infusion Pumps, Implantable; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000627:therapeutic use; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D009368:Neoplasm Transplantation; D009995:Osmosis; D010610:Pharyngeal Neoplasms / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D016037:Single-Blind Method; D047368:Tumor Burden
D019496:Cancer Vaccines; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007213:Indomethacin