Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses |
| |
Authors: | Priscilla F McAuliffe MD William R Jarnagin MD Paul Johnson PhD Keith A Delman MD Howard Federoff MD PhD Yuman Fmg MD |
| |
Institution: | (1) Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., 10021 New York, NY;(2) University of Rochester, Rochester, N.Y;(3) NeuroVir Therapeutics, Inc., San Diego, Calif |
| |
Abstract: | Pancreatic cancer is an aggressive, rapidly fatal disease against which current nonsurgical therapy has minimal impact. This
study evaluates the efficacy of two novel, replication-competent, multimutated herpes viruses (G207 and NV1020) in an experimental
model of pancreatic cancer. Four human pancreatic carcinoma cell lines were exposed to G207 or NV1020, and cell survival and
viral progeny production were determined. Flank tumors in athymic mice were subjected to single or multiple injections of
1 X 107 G207 or NV1020, and tumor volume was evaluated over time. For all of the cell lines, G207 and NV1020 produced infection,
viral replication, and cell lysis (P <0.05). NV1020 resulted in a higher production of viral progeny compared to G207. The
efficacy of viral tumor cell kill was greatest in those cells with the shortest in vitro doubling time. For flank tumors derived
from hs766t, single or multiple injections of both viruses were equally effective and significantly reduced flank tumor burden
(P <0.05). Complete hs766t flank tumor eradication was achieved in 25% (5 of 20) of animals treated with G207 and 40% (8 of
20) of animals treated with NV1020. In vivo efficacy correlated with in vivo tumor doubling time. There were no adverse effects
related to viral administration observed in any animal. NV1020 and G2O7 effectively infect and kill human pancreatic cancer
cells in vitro and in vivo. Given the lack of effective nonoperative treatments for pancreatic cancer, oncolytic herpes viruses
should be considered for clinical evaluation.
Presented in part at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif.,
May 21–24, 2000. |
| |
Keywords: | G2O7 NV1020 pancreatic carcinoma R7020 herpes simplex virus HSV-1 HSV-2 gene therapy |
本文献已被 SpringerLink 等数据库收录! |
|