GM-CSF gene therapy using adenoviral vector in hamster pancreatic cancer

J Hepatobiliary Pancreat Surg. 2000;7(3):306-11. doi: 10.1007/s005340070053.

Abstract

The aim of this study was to examine the antitumor effect of irradiated granulocyte macrophage-colony-stimulating factor (GM-CSF)-gene-transduced hamster pancreatic cancer cells and its relationship to the amount of GM-CSF produced by transduced tumor cells. Hamster pancreatic adenocarcinoma cells, HPD1NR, which spontaneously secrete 15.0+/-0.4 pg/106 cells per 24 h of GM-CSF, and HPD2NR cells, which do not secrete GM-CSF, were used. When these cells were infected with recombinant adenovirus harboring the GM-CSF gene, HPD1NR and HPD2NR secreted 624.2+/-9.9 and 157.8 +/-5.7 pg/106 cells per 24 h, respectively. Vaccination with irradiated GM-CSF-secreting HPD2NR completely protected syngeneic hamsters challenged with live parental cells. On the other hand, vaccination with irradiated HPD1NR protected 60% of hamsters from tumor development after challenge with parental cells. None of the tumor-free hamsters initially vaccinated with irradiated GM-CSF-producing HPD2NR cells developed tumor upon repeated challenge with parental cells during the entire observation period. Irradiated GM-CSF-gene-transduced hamster pancreatic cells are promising as a novel adjuvant cancer therapy after surgery for primary and metastatic pancreatic cancer. The results indicate the necessity for a therapeutic strategy for cancer based on the cytokine status of tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Cells, Cultured
  • Cricetinae
  • Disease Models, Animal
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors / pharmacology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / therapy*
  • Sensitivity and Specificity
  • Treatment Outcome
  • Vaccination / methods

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor