Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anticarcinoembryonic antigen bispecific adapter

Hua Jung Li, Maaike Everts, Larisa Pereboeva, Svetlana Komarova, Anat Idan, David T. Curiel, Harvey R. Herschman

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCARMFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.

Original languageEnglish
Pages (from-to)5354-5361
Number of pages8
JournalCancer research
Volume67
Issue number11
DOIs
StatePublished - Jun 1 2007

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