GM-CSF gene therapy using adenoviral vector in hamster pancreatic cancer.
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.
Ogawa
T
T
First Department of Surgery, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Kusumoto
M
M
Mizumoto
K
K
Sato
N
N
Nagai
E
E
Ikubo
A
A
Aoki
Y
Y
Tanaka
M
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
D016178:Granulocyte-Macrophage Colony-Stimulating Factor