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Oncotarget. 2016 Jun 28;7(26):39768-39783. doi: 10.18632/oncotarget.9465.

Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells.

Zhang W1, Bao L2,3,4, Yang S5, Qian Z2, Dong M6, Yin L7,8, Zhao Q9, Ge K1, Deng Z1, Zhang J10, Qi F11, An Z2, Yu Y2, Wang Q2, Wu R2, Fan F2, Zhang L12, Chen X13, Na Y13, Feng L7, Liu L1, Zhu Y1, Qin T7, Zhang S1, Zhang Y1, Zhang X2,14,15, Wang J2,16, Yi X2, Zou L10, Xin HW17, Ditzel HJ4,18, Gao H5, Zhang K7, Liu B19,1, Cheng S7.

Author information

1
Department of Immunology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
2
BGI-Shenzhen, Shenzhen 518083, China.
3
Molecular Disease Biology Section, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Danish Cancer Society, DK-2100 Copenhagen, Denmark.
4
Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense C, Denmark.
5
Department of Pulmonary Oncology, Affiliated Hospital, Academy of Military Medical Science, Beijing 100071, China.
6
Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
7
State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
8
Lung Cancer Center, Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, China.
9
Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
10
Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu 610041, China.
11
Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing 100853, China.
12
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 10021, China.
13
Institute of Environmental Health and Related Product Safety, China CDC, Beijing 10021, China.
14
The Guangdong Enterprise Key Laboratory of Human Disease Genomics, BGI-Shenzhen, Shenzhen 518083, China.
15
Shenzhen Key Laboratory of Transomics Biotechnologies, BGI-Shenzhen, 518083 Shenzhen, China.
16
James D. Watson Institute of Genome Science, 310008 Hangzhou, China.
17
Laborartory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China.
18
Department of Oncology, Odense University Hospital, DK-5000 Odense C, Denmark.
19
Hubei Provincial Cooperative, Innovation Center of Industrial Fermentation, Hubei University of Technology, Wuhan 30068, China.

Abstract

Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326 blood samples from patients with 6 different solid organ carcinomas and lymphomas. Significantly, CTC-positive rates increased remarkably with tumor progression from N0M0, N+M0 to M1 in each of 5 tested cancers (lung, colon, liver, gastric and pancreatic cancer, and glioma). Among 21 non-small cell lung cancer cases in which CTC values were consecutively monitored, 81% showed treatment-related decreases, which was also found after treatments in the other solid tumors. Moreover, monitoring CTC values provided an efficient treatment response indicator in hematological malignancies. Compared to CellSearch, our method detected significantly higher positive rates in 40 NSCLC in all stages, including N0M0, N+M0 and M1, and was less affected by chemotherapy. This simple, robust and clinically-applicable technology detects viable CTCs from solid and hematopoietic malignancies in early to late stages, and significantly improves clinical detection and treatment prognostication.

KEYWORDS:

clinical application; epithelial-marker-independent; telomerase-specific HSV; viable circulating tumor cells

PMID:
27206795
PMCID:
PMC5129969
DOI:
10.18632/oncotarget.9465
[Indexed for MEDLINE]
Free PMC Article

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