Research Updates

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JULY 2014

PRESS RELEASE
SUBJECT LINE: Okayama University Research: Innovative non-invasive ‘liquid biopsy’
method to capture circulating tumor cells from blood samples for genetic testing
Source: Okayama University, Planning and Public Information Division
For immediate release: 10 July 2014
(Okayama, Japan, 10 July 2014) Okayama University medical researchers seek partners
to commercialize their clinically proven non-invasive fluorescence virus-guided capturesystem of human colorectal circulating tumor cells (CTCs) from blood samples forgenetic testing. This form of non-invasive companion diagnostics is important for
personalized targeted cancer therapy.
The research is led by Professor Toshiyoshi Fujiwara, Okayama University Graduate
School of Medicine, Dentistry, and Pharmaceutical Sciences and was published in Gut
May 2014 [1]The key factor in capturing extremely low quantities of live CTCs from millions ofbackground blood leukocytes is targeting the high telomerase activity of malignant
tumor cells with green fluorescent protein (GFP) expressing telomerase specificreplication adenovirus (OBP-401, TelomeScan [2,3]).
Notably, Professor Fujiwara and colleagues have previously reported on clinical tests on
OBP-401 based GFP labelling to detect live CTCs in gasterointestinal and ovariancancers.
Here, Professor Fujiwara and his team show that their OBP-401 based CTC capturesystem enables the monitoring of genetic mutations in both epithelial andmesenchymal types of CTCs, thereby opening up the possibility of a new non-invasive
companion diagnostic method for genetic testing and personalized medicine.
“This ‘liquid biopsy’ via a simple blood test could be carried out in real time andenables optimized and timely decisions for therapeutic intervention,” state theresearchers.
OKAYAMA UNIVERSITY
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 JAPAN© 2014 OKAYAMA UNIV.

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Background and relevance of this research
In 1869 Thomas Ashworth first reported the presence of circulating tumor cells (CTCs)
in patients with advanced cancer in his paper entitled: "A case of cancer in which cells
similar to those in the tumors were seen in the blood after death". (Australian MedicalJournal 14: 146–7, (1869)).
However, it is challenging to detect CTCs because there are very small quantities ofCTCs in the bloodstream. The so-called CellSearch system is widely used to detect CTCs,
where antibodies are used to target the major epithelial cell surface marker known as
the epithelial cell adhesion molecule (EpCAM).
Importantly, recent research has shown the existence of heterogeneous CTCs that haveboth epithelial and mesenchymal characteristics. This discovery has led to demand forthe development of CTC capture systems that are able to detect CTCs irrespective of
the epithelial cell marker for cancer treatment with molecularly targeted drugs.
Another important fact is that currently, targeted cancer treatment for individual
patients is carried out by analysis of primary tumors. The difficulties with this approach
are that the primary tumors contain very few cells that cause metastasis orreoccurrence, and samples for analysis are obtained by needle core biopsies or surgicalremoval of tumor tissue—which are invasive procedures and prohibit the extraction oftissue from locations inaccessible by surgery.
So there is the need for non-invasive methods capable of detecting CTCs independentof the epithelial cell marker.
Details and conclusions described in Gut [1](1) The OBP-401-based CTC capture system developed by Okayama University can beused to genetic testing of CTCs with mesenchymal characteristics, including GISTs andosteosarcomas.
(2) Combining OBP-401-based CTC capture system and genetic testing enabled thedetection of KRAS and BRAF mutations in blood samples taken from patients withcolorectal cancer. Notably, these mutations were determined to be identical to theones seen in the primary tumours of the patients.
OKAYAMA UNIVERSITY
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 JAPAN© 2014 OKAYAMA UNIV.

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JULY 2014(3) This technology requires large scale testing.

References and information[1] Shigeyasu K, Tazawa H, Hashimoto Y,et al., Fluorescence virus-guided capturingsystem of human colorectal circulating tumour cells for non- invasive companion
diagnostics, Gut Published Online First: [28 May 2014] doi:10.1136/gutjnl-2014-306957
Correspondence toProfessor Toshiyoshi Fujiwara,
Department of Gastroenterological Surgery, Okayama
University Graduate School of Medicine, Dentistry andPharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku,Okayama 700-8558, JapanEMAIL: toshi_f@md.okayama-u.ac.jp

OKAYAMA UNIVERSITY
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 JAPAN© 2014 OKAYAMA UNIV.

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JULY 2014[2] The manufacturer of OBP-401 (TelomeScan) is Oncolys BioPharma Inc:
http://www.oncolys.com/en/pipeline/obp-1101.html[3] Patents owned by Oncolys BioPharma Inc:
http://www.oncolys.com/en/company-information/patent.html
Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku ,Okayama 700-8530, Japan
Planning and Public Information Division, Okayama University
E-mail: www-adm@adm.okayama-u.ac.jp
Website: http://www.okayama-u.ac.jp/index_e.html

About Okayama UniversityOkayama University is one of the largest
comprehensive universities in Japan withroots going back to the Medical Training
Place sponsored by the Lord of Okayama
and established in 1870. Now with 1,300
faculty and 14,000 students, the University
offers courses in specialties ranging frommedicine and pharmacy to humanities
and physical sciences. Okayama
University is located in the heart of Japan
approximately 3 hours west of Tokyo byShinkansen.

Website: http://www.okayama-u.ac.jp/index_e.html

OKAYAMA UNIVERSITY
1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 JAPAN© 2014 OKAYAMA UNIV.