TY - JOUR
T1 - A combinatory strategy for detection of live CTCs using microfiltration and a new telomerase-selective adenovirus
AU - Ma, Yanchun
AU - Hao, Sijie
AU - Wang, Shuwen
AU - Zhao, Yuanjun
AU - Lim, Bora
AU - Lei, Ming
AU - Spector, David J.
AU - El-Deiry, Wafik S.
AU - Zheng, Si Yang
AU - Zhu, Jiyue
N1 - Funding Information:
The authors thank Dr. Richard Stanton of Cardiff University for adenoviral BAC constructs. D.J. Spector thanks Richard Courtney and members of the Department of Microbiology and Immunology for their support. This work was supported by the NIH grants R03CA165182 and R01GM071725 (to J. Zhu) and DP2CA174508 (to S.-Y. Zheng). J. Zhu was also supported by the W.W. Smith Charitable Trust.
Publisher Copyright:
© 2015 American Association for Cancer Research.
PY - 2015/3
Y1 - 2015/3
N2 - 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.
AB - 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.
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U2 - 10.1158/1535-7163.MCT-14-0693
DO - 10.1158/1535-7163.MCT-14-0693
M3 - Article
C2 - 25589497
AN - SCOPUS:84942086661
SN - 1535-7163
VL - 14
SP - 835
EP - 843
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 3
ER -