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Effective treatment of pancreatic tumors with two multimutated herpes simplex oncolytic viruses
P F McAuliffe1, W R Jarnagin, P Johnson
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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 10(7) 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 G207 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.
Insights
Novel oncolytic herpes viruses, G207 and NV1020, show promise in treating pancreatic cancer. These viruses effectively infected and destroyed cancer cells in laboratory and animal models, offering a potential new therapeutic avenue.
Area of Science:
- Oncolytic virology
- Cancer biology
- Immunotherapy
Background:
- Pancreatic cancer is a highly aggressive malignancy with limited effective nonsurgical treatment options.
- Current therapies offer minimal impact on patient survival and disease progression.
Purpose of the Study:
- To evaluate the efficacy of two novel oncolytic herpes viruses, G207 and NV1020, against human pancreatic cancer cells.
- To assess the in vitro and in vivo anti-tumor activity of these viruses in experimental pancreatic cancer models.
Main Methods:
- Human pancreatic carcinoma cell lines were exposed to G207 or NV1020 to determine cell survival and viral replication.
- Athymic mice with flank tumors received single or multiple injections of G207 or NV1020 to evaluate tumor volume reduction.
- In vitro and in vivo tumor doubling times were correlated with viral efficacy.
Main Results:
- Both G207 and NV1020 successfully infected, replicated within, and lysed pancreatic cancer cells in vitro (P < 0.05).
- NV1020 demonstrated higher viral progeny production compared to G207.
- In vivo, both viruses significantly reduced tumor burden, with complete eradication achieved in 25% (G207) and 40% (NV1020) of animals.
- Viral efficacy correlated with tumor doubling time, and no adverse effects were observed.
Conclusions:
- Oncolytic herpes viruses G207 and NV1020 are effective in infecting and killing human pancreatic cancer cells both in vitro and in vivo.
- These findings support the clinical evaluation of oncolytic herpes viruses as a potential therapeutic strategy for pancreatic cancer.
- The lack of effective nonoperative treatments underscores the need for novel approaches like oncolytic virotherapy.