Interferon Alpha-Expressing Oncolytic Adenovirus for Treatment of Esophageal Adenocarcinoma

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: Esophageal adenocarcinoma (EAC) has increased in incidence in Western countries, and its poor prognosis necessitates the development of novel therapeutics. We previously reported the potential of conditionally replicative adenoviruses (CRAd) as a novel therapeutic treatment for this disease. To further augment the therapeutic effectiveness of our cyclooxygenase-2 (Cox2) controlled CRAd in EAC, we inserted an interferon alpha (IFN) transgene into the viral genome that is expressed upon viral replication. In this manuscript, we analyze the cytotoxic and oncolytic effects of an IFN-expressing oncolytic adenovirus in EAC and the role of the Cox2 promoter in providing for selective replication in human tissues. Methods: An infectivity-enhanced IFN-expressing CRAd (5/3 Cox2 CRAd ΔE3 ADP IFN) and other control viruses were first tested in vitro with cell lines. For the in vivo study, EAC xenografts in nude mice were treated with a single intratumoral dose of virus. An ex vivo analysis with live tissue slices was conducted using surgically resected EAC patient specimens. Results: Expression of IFN significantly enhanced the cytotoxic and oncolytic effect of a Cox2-promoter controlled CRAd. This virus showed significant tumor growth suppression in a xenograft model. Furthermore, in human EAC samples, the promoter-controlled virus demonstrated selective replication in cancerous tissues, leaving normal esophageal tissue unaffected. Conclusion: An IFN-expressing CRAd driven by the Cox2 promoter has strong oncolytic effects as well as cancer-specific replication. Our novel vector possesses critical characteristics that make it a potential candidate for clinical translation to treat EAC.

Original languageEnglish (US)
Pages (from-to)8556-8564
Number of pages9
JournalAnnals of Surgical Oncology
Volume28
Issue number13
Early online dateJul 29 2021
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
The project is partly supported by NIH/NCI R01CA228760-01A1 (MY/JD) and a University of Minnesota-VFW Surgical Oncology Research Award (C.J.L.).

Publisher Copyright:
© 2021, Society of Surgical Oncology.

Keywords

  • Adenocarcinoma/therapy
  • Adenoviridae/genetics
  • Animals
  • Cell Line, Tumor
  • Humans
  • Interferon-alpha
  • Mice
  • Mice, Nude
  • Oncolytic Virotherapy

PubMed: MeSH publication types

  • Journal Article

Fingerprint

Dive into the research topics of 'Interferon Alpha-Expressing Oncolytic Adenovirus for Treatment of Esophageal Adenocarcinoma'. Together they form a unique fingerprint.

Cite this