Efficacy of an osmotic pump delivered, GM-CSF-based tumor vaccine in the treatment of upper aerodigestive squamous cell carcinoma in rats

Hamid R. Djalilian, Emiro Caicedo, Khashayar Lessan, Vahid Grami, Chap T. Le, Stephen R. Spellman, Stephan Pambuccian, Walter A. Hall, Walter C. Low, Frank G. Ondrey

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Purpose: 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; 106 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1207-1214
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume56
Issue number8
DOIs
StatePublished - Aug 2007

Bibliographical note

Funding Information:
Acknowledgments Supported by the American Academy of Otolaryngology—Head and Neck Surgery Foundation Resident Research Award and the Lion’s 5M hearing center grant.

Keywords

  • Head and neck cancer
  • Immunotherapy
  • Interleukin 12
  • Rat model

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