Noninvasive dual modality in vivo monitoring of the persistence and potency of a tumor targeted conditionally replicating adenovirus

A. Kanerva, K. R. Zinn, K. W. Peng, T. Ranki, L. Kangasniemi, T. R. Chaudhuri, R. A. Desmond, M. Wang, K. Takayama, T. Hakkarainen, H. Alfthan, U. H. Stenman, D. T. Curiel, A. Hemminki

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

In clinical trials with cancer patients, the safety of conditionally replicating adenoviruses (CRAds) has been good. However, marginal data are available on the persistence or antitumor efficacy of these agents. The oncolytic potency of CRAds is determined by their capacity for entering target cells. Consequently, we constructed a retargeted CRAd featuring a secreted marker protein, soluble human carcinoembryogenic antigen (hCEA), which can be measured in growth medium or plasma. We found that virus replication closely correlated with hCEA secretion both in vitro and in vivo. Further, antitumor efficacy and the persistence of the virus could be deduced from plasma hCEA levels. Finally, using in vivo bioluminescence imaging, we were able to detect effective tumor cell killing by the virus, which led to enhanced therapeutic efficacy.

Original languageEnglish (US)
Pages (from-to)87-94
Number of pages8
JournalGene Therapy
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • Adenovirus
  • Imaging
  • Ovarian neoplasms
  • Virus replication

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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