Oncolytic adenovirus expressing interferon alpha in a syngeneic Syrian hamster model for the treatment of pancreatic cancer

Surgery
Christopher J LaRoccaJulia Davydova

Abstract

The addition of interferon (IFN) alpha to adjuvant chemoradiotherapy regimens resulted in remarkable improvements in survival for pancreatic cancer patients. However, systemic toxicities and insufficient levels of IFN at the tumor sites have limited its widespread adoption in treatment schemes. We have previously developed an IFN-expressing conditionally replicative oncolytic adenovirus and demonstrated its therapeutic effects both in vitro and in vivo. Here, the same vectors were tested in a syngeneic and immunocompetent Syrian hamster model to better understand the roles of adenoviral replication and of the pleiotropic effects of IFN on pancreatic tumor growth suppression. Oncolytic adenoviruses expressing human or hamster IFN were designed and generated. Viral vectors were tested in vitro to determine qualitative and quantitative cell viability, cyclooxygenase 2 (Cox2) promoter activity, and IFN production. For the in vivo studies, subcutaneous hamster pancreatic cancer tumors were treated with 1 intratumoral dose of virus. Similarly, 1 intraperitoneal dose of virus was used to prolong survival in a carcinomatosis model. All cell lines tested demonstrated Cox2 promoter activity. The oncolytic potential of a replication compe...Continue Reading

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Citations

Jul 6, 2016·Current Opinion in Virology·Amanda Rosewell Shaw, Masataka Suzuki
Apr 4, 2018·Cancers·Mizuho Sato-DahlmanMasato Yamamoto
May 26, 2017·Biomedicines·Alexander S Dash, Manish R Patel
May 26, 2017·Biomedicines·Jing Li HuangMasato Yamamoto
Nov 8, 2018·Biomedicines·Christopher J LaRocca, Susanne G Warner
May 28, 2020·Cancers·Mizuho Sato-DahlmanMasato Yamamoto
Nov 15, 2018·Clinical and Translational Medicine·Christopher J LaRocca, Susanne G Warner
Nov 25, 2020·Expert Opinion on Drug Discovery·Shunchuan Zhang, Samuel D Rabkin
Dec 2, 2020·Journal for Immunotherapy of Cancer·Louis LantierIsabelle Dimier-Poisson
Dec 25, 2019·Molecular Therapy Oncolytics·Meijun ZhengHui Yang
Feb 14, 2021·Cancers·Kerry FisherLeonard W Seymour
Nov 19, 2020·Cancers·Malin Peter, Florian Kühnel
Apr 6, 2021·Molecular Therapy Oncolytics·Matthew Glen RobertsonJulia Davydova
Jul 30, 2021·Annals of Surgical Oncology·Christopher J LaRoccaMasato Yamamoto

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