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Active immunotherapy of pancreatic cancer with tumor cells genetically engineered to secrete multiple cytokines.

Publication ,  Journal Article
Clary, BM; Coveney, EC; Blazer, DG; Philip, R; Lyerly, HK
Published in: Surgery
August 1996

BACKGROUND: Vaccination of tumor-bearing animals with tumor cells genetically engineered to secrete cytokines including interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) has been shown to induce effective tumor-specific immune responses capable of inhibiting local and metastatic disease. Previous unsuccessful attempts to enhance this immune response by means of the secretion of multiple cytokines possessing different immunologic mechanisms of action may have been due to the inherent inefficiency of the gene transfer systems used. We postulated that tumor cells genetically engineered by means of a novel gene transfer method resulting in high level secretion of both cytokines would be more effective than tumor cells secreting a single cytokine in inhibiting the growth of existing tumors. METHODS: Nonimmunogenic, murine pancreatic cancer cells (Panc02) were engineered to secrete IL-2, IFN-gamma, IL-2 and IFN-gamma, or neomycin phosphotransferase. Mice were inoculated with 5 x 10(5) parental Panc02 tumor cells subcutaneously. Beginning 3 days later, animals then received a series of four weekly vaccinations with irradiated Panc02/Neo, Panc02/IL2, Panc02/IFN, or Panc02/IL-2/IFN. RESULTS: Treatment with Panc02/Neo, Panc02/IL-2, or Panc02/IFN resulted in 0%, 40%, and 30% tumor-free survival, respectively. In contrast, 80% of animals vaccinated with Panc02/IL2/IFN were free of tumor at 100 days. All animals free of disease were resistant to subsequent tumor challenges. CONCLUSIONS: These data show that vaccination with tumor cells that secrete high levels of multiple cytokines was more effective in treating established pancreatic tumors and represents an improvement over existing single cytokine strategies.

Duke Scholars

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

August 1996

Volume

120

Issue

2

Start / End Page

174 / 181

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Surgery
  • Plasmids
  • Pancreatic Neoplasms
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Interleukin-2
  • Interferon-gamma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Clary, B. M., Coveney, E. C., Blazer, D. G., Philip, R., & Lyerly, H. K. (1996). Active immunotherapy of pancreatic cancer with tumor cells genetically engineered to secrete multiple cytokines. Surgery, 120(2), 174–181. https://doi.org/10.1016/s0039-6060(96)80285-6
Clary, B. M., E. C. Coveney, D. G. Blazer, R. Philip, and H. K. Lyerly. “Active immunotherapy of pancreatic cancer with tumor cells genetically engineered to secrete multiple cytokines.Surgery 120, no. 2 (August 1996): 174–81. https://doi.org/10.1016/s0039-6060(96)80285-6.
Clary BM, Coveney EC, Blazer DG, Philip R, Lyerly HK. Active immunotherapy of pancreatic cancer with tumor cells genetically engineered to secrete multiple cytokines. Surgery. 1996 Aug;120(2):174–81.
Clary, B. M., et al. “Active immunotherapy of pancreatic cancer with tumor cells genetically engineered to secrete multiple cytokines.Surgery, vol. 120, no. 2, Aug. 1996, pp. 174–81. Pubmed, doi:10.1016/s0039-6060(96)80285-6.
Clary BM, Coveney EC, Blazer DG, Philip R, Lyerly HK. Active immunotherapy of pancreatic cancer with tumor cells genetically engineered to secrete multiple cytokines. Surgery. 1996 Aug;120(2):174–181.
Journal cover image

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

August 1996

Volume

120

Issue

2

Start / End Page

174 / 181

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Surgery
  • Plasmids
  • Pancreatic Neoplasms
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Interleukin-2
  • Interferon-gamma