Active immunization with tumor cells transduced by a novel AAV plasmid- based gene delivery system

Bryan M. Clary, Eamonn C. Coveney, Dan G. Blazer, Ramila Philip, Mohan Philip, Michael Morse, Eli Gilboa, H. Kim Lyerly

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Ex vivo genetically engineered cytokine-secreting tumor cell vaccines have been shown to prevent metastatic disease in animal models of lung and breast cancer. Because of the inefficiency of existing modes of gene delivery in transducing primary human tumor cells, it has been difficult to clinically apply this strategy. In this study, liposome-mediated delivery of an adeno- associated virus (AAV)-based plasmid containing the sequence for murine γ- interferon (γ-IFN) (pMP6A-mIFN-γ) was used to generate cytokine-secreting murine tumor cell vaccines. High levels of γ-IFN and elevated class I major histocompatibility complex expression after transfer of pMP6A-mIFN-γ into the murine lung cancer cell line, D122, was demonstrated. The efficiency of gene transfer was determined by two different methods and was estimated to be 10-15%. Irradiated γ-IFN D122 cells generated by this novel gene delivery system (D122/pMP6A-mIFN-γ) and also by standard retroviral methods (DIF2) were administered as weekly vaccinations by intraperitoneal injection to animals bearing 7-day-old intrafootpad D122 tumors. Hindlimb amputation was performed when footpad diameters reached 7 mm, and lungs were harvested 28 days later. Animals vaccinated with γ-IFN-secreting D122 cells produced by AAV-based plasmids delivery demonstrated a significant delay in foot-pad tumor growth when compared with controls and DIF2 cells. Fifty-seven percent of animals vaccinated with D122/pMP6A-mIFN-γ were free of pulmonary metastases 28 days after amputation, significantly improved from the 0, 7, and 15% observed in animals vaccinated with irradiated parental D122 cells, irradiated D122 cells lipofected with an empty-cassette vector (pMP6A), or DIF2 cells, respectively. These results and the ability to transfer genes with this delivery system to a broad range of tumor types support its use in the generation of cytokine-secreting tumor cell vaccinations for use in clinical trials.

Original languageEnglish
Pages (from-to)26-37
Number of pages12
JournalJournal of Immunotherapy
Volume20
Issue number1
DOIs
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

Gene Transfer Techniques
Dependovirus
Vaccination
Plasmids
Neoplasms
Cancer Vaccines
Cytokines
Amputation
Lung Neoplasms
Animal Disease Models
Lung
Hindlimb
Major Histocompatibility Complex
Intraperitoneal Injections
Liposomes
Interferons
Genes
Foot
Clinical Trials
Breast Neoplasms

Keywords

  • Cytokine
  • Gene therapy
  • Tumor vaccines

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Clary, B. M., Coveney, E. C., Blazer, D. G., Philip, R., Philip, M., Morse, M., ... Lyerly, H. K. (1997). Active immunization with tumor cells transduced by a novel AAV plasmid- based gene delivery system. Journal of Immunotherapy, 20(1), 26-37. https://doi.org/10.1097/00002371-199701000-00003

Active immunization with tumor cells transduced by a novel AAV plasmid- based gene delivery system. / Clary, Bryan M.; Coveney, Eamonn C.; Blazer, Dan G.; Philip, Ramila; Philip, Mohan; Morse, Michael; Gilboa, Eli; Lyerly, H. Kim.

In: Journal of Immunotherapy, Vol. 20, No. 1, 01.12.1997, p. 26-37.

Research output: Contribution to journalArticle

Clary, Bryan M. ; Coveney, Eamonn C. ; Blazer, Dan G. ; Philip, Ramila ; Philip, Mohan ; Morse, Michael ; Gilboa, Eli ; Lyerly, H. Kim. / Active immunization with tumor cells transduced by a novel AAV plasmid- based gene delivery system. In: Journal of Immunotherapy. 1997 ; Vol. 20, No. 1. pp. 26-37.
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