TY - JOUR
T1 - Therapeutic efficacy of G207, a conditionally replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters
AU - Nakano, Kenji
AU - Todo, Tomoki
AU - Chijiiwa, Kazuo
AU - Tanaka, Masao
N1 - Funding Information:
We thank Dr. Robert L. Martuza (Harvard Medical School, Boston, MA) for helpful discussion and Dr. Paul Johnson (NeuroVir Therapeutics, San Diego, CA) for providing purified G207. This work was partly supported by Grants-in-Aid from the Japanese Minister of Science and Culture (07671406 and 09671318 for K.C.) and a Grant-in-Aid for Cancer Research from the Fukuoka Cancer Society, Fukuoka, Japan (K.N.).
PY - 2001
Y1 - 2001
N2 - Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 × 107 pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.
AB - Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 × 107 pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.
UR - http://www.scopus.com/inward/record.url?scp=0034980707&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034980707&partnerID=8YFLogxK
U2 - 10.1006/mthe.2001.0303
DO - 10.1006/mthe.2001.0303
M3 - Article
C2 - 11319903
AN - SCOPUS:0034980707
VL - 3
SP - 431
EP - 437
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 4
ER -