Abstracts
2000 Digestive Disease Week

# 2454 Effective Treatment of Pancreatic Tumors with Two Multimutated Herpes Simplex Oncolytic Viruses.
William Jarnagin, Priscilla McAuliffe, Howard Federoff, Paul Johnson, Yuman Fong, New York, NY, Rochester, NY

Pancreatic cancer is an aggressive malignancy against which current therapy have limited success. Two replication competent, multimutated herpes viruses (G207 and NV1020) were tested for efficacy against pancreatic tumors. These viruses are modified to target tumor, while sparing normal tissue. G207 has had both copies of the g134.5 gene deleted, whereas NV1020 has had only 1 copy deleted. This mutation results in attenuating neurovirulence. Methods: In vitro: Cytotoxicity was assessed for 4 human pancreatic carcinoma cell lines exposed to G207 or NV1020 at multiplicity of infection (MOI: ratio of virus to cells) of 0, 0.01, 0.1 and 1. In vivo: 2x106 HTB134 cells were implanted on flanks of athymic mice. When tumors reached 30 mm3, they were directly injected with either G207 or NV1020 (1x107viruses), or with serum-free media (n=20/treatment group). Results: In vitro: Cytotoxicity of G207 or NV1020 was significantly greater than control in all four cell lines (p<0.001; Student s T test) (Table). For MOI 0.01 and 0.1, cytotoxicity of the viruses was significant after 48 hours in all four cell lines. The difference in cytotoxicity between the two viruses was not significant. In vivo: Compared to control, flank tumor burden was suppressed by all treatments (p<0.01; Student’s T test). Complete flank tumor eradication was achieved in 30% (6/20) of animals treated with G207 and 40% (8/20) of animals treated with NV1020. No adverse effects related to viral administration were noted in any animal. Conclusions: Both NV1020 and G207 are effective against pancreatic cancer in vitro and are a successful therapy in vivo. The more rapidly growing tumors (shorter doubling time) had a markedly greater response in vitro. Both viruses demonstrated a significant rate of complete cure, with NV1020 conferring a higher rate of complete responders. Oncolytic herpes viruses are a promising novel therapy for pancreatic tumors Percent cells surviving at 96 hours