Efficient oncolysis by a replicating adenovirus (Ad) in vivo is critically dependent on tumor expression of primary Ad receptors

Joanne T. Douglas, Myunghee Kim, Lucretia A. Sumerel, Delicia E. Carey, David T. Curiel

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

Replicating adenoviruses (Ads) are designed to replicate in and destroy cancer cells, generating viral progeny that spread within the tumor. To address the importance of the primary cellular receptor for Ads, the coxsackievirus and Ad receptor (CAR), in permitting intratumoral spread of a replicating Ad, we have used a pair of tumor cell lines differing only in the expression of a primary receptor for Ad5. This novel system thus allowed the first direct evaluation of the relationship between the efficacy of a replicating Ad and the primary receptor levels of the host cell without the confounding influence of other variable cellular factors. We demonstrate that the absence of the primary cellular receptor on the tumor cells restricts the oncolytic potency of a replicating Ad both in vitro and in vivo. Based on these findings, it is apparent that the potential therapeutic afforded by viral replication would be negated by poor intra-advantages tumoral spread of the viral progeny due to the failure to infect neighboring tumor cells. Because a number of studies have reported that primary cancer cells express only low levels of CAR, our results suggest that strategies to redirect Ads to achieve CAR-independent infection will be necessary to realize the full potential of replicating Ads in the clinical setting.

Original languageEnglish
Pages (from-to)813-817
Number of pages5
JournalCancer research
Volume61
Issue number3
StatePublished - Feb 1 2001
Externally publishedYes

Fingerprint Dive into the research topics of 'Efficient oncolysis by a replicating adenovirus (Ad) in vivo is critically dependent on tumor expression of primary Ad receptors'. Together they form a unique fingerprint.

  • Cite this