A combinatory strategy for detection of live CTCs using microfiltration and a new telomerase-selective adenovirus

Yanchun Ma, Sijie Hao, Shuwen Wang, Yuanjun Zhao, Bora Lim, Ming Lei, David J. Spector, Wafik S. El-Deiry, Si Yang Zheng, Jiyue Zhu

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Circulating tumor cells (CTC) have become an important biomarker for early cancer diagnosis, prognosis, and treatment monitoring. Recently, a replication-competent recombinant adenovirus driven by a human telomerase gene (hTERT) promoter was shown to detect live CTCs in blood samples of patients with cancer. Here, we report a new class of adenoviruses containing regulatory elements that repress the hTERT gene in normal cells. Compared with the virus with only the hTERT core promoter, the new viruses showed better selectivity for replication in cancer cells than in normal cells. In particular, Ad5GTSe, containing three extra copies of a repressor element, displayed a superior tropism for cancer cells among leukocytes and was thus selected for CTC detection in blood samples. To further improve the efficiency and specificity of CTC identification, we tested a combinatory strategy of microfiltration enrichment using flexible micro spring arrays and Ad5GTSe imaging. Our experiments showed that this method efficiently detected both cancer cells spiked into healthy blood and potential CTCs in blood samples of patients with breast and pancreatic cancer, demonstrating its potential as a highly sensitive and reliable system for detection and capture of CTCs of different tumor types.

Original languageEnglish (US)
Pages (from-to)835-843
Number of pages9
JournalMolecular cancer therapeutics
Volume14
Issue number3
DOIs
StatePublished - Mar 2015

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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