Cancer imaging and therapy utilizing a novel NIS-expressing adenovirus: The role of adenovirus death protein deletion

Matthew Glen Robertson, Benjamin Bruce Eidenschink, Eriko Iguchi, Stanislav O. Zakharkin, Christopher J. LaRocca, Ezequiel J. Tolosa, Mark J. Truty, Kari Jacobsen, Martin E. Fernandez-Zapico, Julia Davydova

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Encoding the sodium iodide symporter (NIS) by an adenovirus (Ad) is a promising strategy to facilitate non-invasive imaging and radiotherapy of pancreatic cancer. However, insufficient levels of NIS expression in tumor cells have limited its clinical translation. To optimize Ad-based radiotherapy and imaging, we investigated the effect of Ad death protein (ADP) deletion on NIS expression. We cloned two sets of oncolytic NIS-expressing Ads that differed only in the presence or absence of ADP. We found that ADP expression negatively affected NIS membrane localization and inhibited radiotracer uptake. ADP deletion significantly improved NIS-based imaging in pancreatic cancer models including patient-derived xenografts, where effective imaging was possible for up to 6 weeks after a single virus injection. This study demonstrates that improved oncolysis may hinder the therapeutic effect of oncolytic viruses designed to express NIS. In vivo studies in combination with 131I showed potential for effective radiotherapy. This also highlights the need for further investigation into optimal timing of 131I administration and suggests that repeated doses of 131I should be considered to improve efficacy in clinical trials. We conclude that ADP deletion is essential for effective NIS-based theranostics in cancer.

Original languageEnglish (US)
Pages (from-to)659-668
Number of pages10
JournalMolecular Therapy - Oncolytics
Volume20
DOIs
StatePublished - Mar 26 2021

Bibliographical note

Funding Information:
This study was supported by NIH NCI R01CA174861 (J.D. and M.E.F.-Z.); NIH NCI R01CA228760 (J.D.); NIH NCI P50CA101955 UAB-UMN Pancreatic Cancer SPORE Career Development Award (J.D.); University of Minnesota Masonic Cancer Center CRTI Translational Research Award grant (J.D. and M.G.R.); and Randy Shaver Cancer Research Grant (J.D. and M.G.R.). The authors thank Drs. John Morris (Mayo Clinic) and Lisa Koodie (UMN) for valuable discussions and technical support.

Publisher Copyright:
© 2021 The Authors

Keywords

  • Adenovirus
  • Adenovirus Death Protein
  • Cancer imaging
  • Oncolytic Virus
  • Pancreatic cancer
  • Radiotherapy
  • Sodium-iodide symporter

PubMed: MeSH publication types

  • Journal Article

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