Pf. Mcauliffe et al., Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses, J GASTRO S, 4(6), 2000, pp. 580-587
Pancreatic cancer is an aggressive, rapidly fatal disease against which cur
rent nonsurgical therapy has minimal impact. This study evaluates the effic
acy of two novel, replication-competent, multimutated herpes viruses (G207
and NV1020) in an experimental model of pancreatic cancer. Four human pancr
eatic carcinoma cell lines were exposed to G207 or NV1020, and cell surviva
l and viral progeny production were determined. Flank tumors in athymic mic
e mere subjected to single or multiple injections of 1 x 10(7) G207 or NV10
20, and tumor volume was evaluated over time. For all of the cell lines, G2
07 and NV1020 produced infection, viral replication, and cell lysis (P <0.0
5). NV1020 resulted in a higher production of Viral progeny compared to G20
7. The efficacy of viral tumor cell kill was greatest in those cells with t
he shortest in vitro doubling time. For flank tumors derived from hs766t, s
ingle or multiple injections of both viruses were equally effective and sig
nificantly reduced flank tumor burden (P <0.05). Complete hs766t flank tumo
r eradication was achieved in 25% (5 of 20) of animals treated with G207 an
d 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 G207 effectively i
nfect and kill human pancreatic cancer cells in vitro and in vivo. Given ti
le lack of effective nonoperative treatments for pancreatic cancer, oncolyt
ic herpes viruses should be considered for clinical evaluation.