Objective: To assess immune-based gene therapy in a murine floor of mouth (FOM) squamous cell carcinoma (SCC) model.
Study Design: In vitro and in vivo testing of immune therapy for SCC.
Methods: Multiple SCC lines were infected by using advRSV-interleukin-12 (IL-12) and advCMV-interleukin-12/granulocyte macrophage colony-stimulating factor (IL-12/GM-CSF) and monitored for production of IL-12 and GM-CSF. Intratumoral injections of viral vectors were administered with systemic Ig-4-1BB ligand in an orthotopic murine FOM SCC model and followed for tumor size and survival.
Results: In vitro, all cell lines produced substantial levels of IL-12 and GM-CSF. In vivo, tumors treated with advCMV-IL-12/GM-CSF and Ig-4-1BBL showed a striking reduction in tumor volume (vs control P<0.0001) and improved median survival (38 days vs 19 days for control, P<0.0001).
Conclusion: Combination immune-based therapies effectively improve survival in mice bearing FOM SCC over single-modality therapy.
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http://dx.doi.org/10.1016/j.otohns.2008.05.001 | DOI Listing |
Otolaryngol Head Neck Surg
September 2008
Department of Otolaryngology-Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York 10003-4297, USA.
Objective: To assess immune-based gene therapy in a murine floor of mouth (FOM) squamous cell carcinoma (SCC) model.
Study Design: In vitro and in vivo testing of immune therapy for SCC.
Methods: Multiple SCC lines were infected by using advRSV-interleukin-12 (IL-12) and advCMV-interleukin-12/granulocyte macrophage colony-stimulating factor (IL-12/GM-CSF) and monitored for production of IL-12 and GM-CSF.
Gene Ther
October 2005
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, NY 10029, USA.
We have previously shown that the local-membrane bound 4-1BB ligand and IL-12 gene transfer induced a significant antitumor response in a mouse colon carcinoma model. However, a high viral dose was required in order to achieve the best efficacy. In this study, we hypothesize that the systemic administration of soluble Ig-4-1BB ligand can give rise to better T-cell immune activation than local gene delivery.
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