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GM‐CSF Gene therapy using adenoviral vector in hamster pancreatic cancer
Author(s) -
Ogawa Takahiro,
Kusumoto Masahiro,
Mizumoto Kazuhiro,
Sato Norihiro,
Nagai Eishi,
Ikubo Akashi,
Aoki Yasuaki,
Tanaka Masao
Publication year - 2000
Publication title -
journal of hepato‐biliary‐pancreatic surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 0944-1166
DOI - 10.1007/s005340070053
Subject(s) - hamster , pancreatic cancer , genetic enhancement , granulocyte macrophage colony stimulating factor , cancer research , cytokine , cancer , adjuvant , biology , adenocarcinoma , cancer cell , secretion , immunology , medicine , microbiology and biotechnology , endocrinology , gene , biochemistry
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/10 6 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/10 6 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.