(OBP-401 and OBP-1101)
OBP-401 or TelomeScan is a genetically engineered adenovirus type 5 to detect tumor cells. TelomeScan has a human Telomerase Reverse Transcriptase (hTERT) gene promoter sequence in the upstream region of virus E1 gene which is responsible for replication of adenovirus, and a Green Fluorescent Protein (GFP) gene in E3 region under the control by cytomegalovirus promoter. TERT is a critical protein component of telomerase enzyme complex, and its expression is normally restricted in germ line cells or few stem cells including hematopoietic stem cells. Cancer cells are essentially acquired immortalized nature and express strong telomerase activity. Thus, OBP-401 can replicate only in telomerase activity-positive cells such as cancer cells by hTERT promoter activity-dependent E1/E2 gene expression, but not in telomerase activity-negative normal cells. Along with the increase in virus replication, concurrently-expressed GFP accumulates in hTERT-positive cells.
By utilizing OBP-401 ex vivo, it is possible to detect living circulating tumor cells (CTCs) in blood from cancer patients with high sensitivity and specificity. CTCs detection would be able to offer a tool for early detection of cancer, monitoring of therapeutic efficacy, monitoring of tumor recurrence, and selection of appropriate therapy to patients.
OBP-1101 is second generation of TelomeScan. Since TelomeScan has two issues to be improved, i.e. false negative and false positive. TelomeScan cannot be infected to some kind of cancer cells which lack adenovirus receptor "CAR" (coxackie-adenovirus receptor) on the cell surface. CAR-lacking cancer cells are regarded as "false negative". In contrast, TelomeScan generates false positive in some white blood cells having hTERT activity. To dissolve these issues, two genetic modifications including change in fibre gene and addition of four tandem-arrayed miR142-3p target sequences were added on OBP-401 vector sequence.
Detection of circulating tumor cells (CTCs)
Oncolys currently focuses on development of TelomeScan to detect CTCs in cancer patients and also provide clinical testing service to detect CTCs. Oncolys aims to get regulatory approval from Japanese PMDA and have been preparing regulatory consultation with the agency.
In December 2014, Oncolys out-licensed an exclusive license of OBP-1101 for South Korea to a listed South Korean company, WonikCube. WonikCube has been developing OBP-1101 in order to get regulatory approval in this territory.
In November 2015, Oncolys signed an exclusive license agreement for the North American territory with Liquid Biotech USA, Inc., founded by University of Pennsylvania and its professors. Liquid Biotech USA has been developing TelomeScan technology for providing CTC detection services to clinicians and pharmaceutical companies.
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Outline：Outline：Detection and monitoring of circulating tumor cells (CTCs) may be useful in patients with early stage non-small lung cancer.
Melissa A. Frick, Gary D. Kao, Louise Aguarin,Chimbu Chinniah, Samuel Swisher-McClure,Abigail T. Berman,William P. Levin,Keith A. Cengel, Cristina DeCesaris, Stephen M. Hahn, Jay F. Dorsey, Charles B. Simone II
『International Journal of Radiation Oncology』 Volume 102, Issue 3, Pages 536–542 November 1, 2018
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Outline：Relationship between therapeutic response and clinicopathological features using the tissue and liquid biopsy (CTC and cfDNA) from squamous cell lung cancer.
Junko Watanabe, Shinsaku Togo, Issei Sumiyoshi, Yukiko Namba, Kentaro Suina, Takafumi Mizuno, Kotaro Kadoya, Hiroaki Motomura, Moe Iwai, Tetsutaro Nagaoka, Shinichi Sasaki, Takuo Hayashi, Toshimasa Uekusa, Kanae Abe, Yasuo Urata, Fuminori Sakurai, Hiroyuki Mizuguchi, Shunsuke Kato and Kazuhisa Takahashi
Oncotarget, 2018; 9:24000-24013
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Megumi Watanabe, Shunsuke Kagawa, Kazuya Kuwada, Yuuri Hashimoto, Kunitoshi Shigeyasu, Michihiro Ishida, Shuichi Sakamoto, Atene Ito, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Kishimoto, Shuta Tomida, Ryuichi Yoshida, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara
Cancer Science, 04 August 2018
- ■Efficient detection of Human circulating tumor cells withoout significant production of false-positive cells by a novel conditionally replicating adenovirus
Fuminori Sakurai, Nobuhiro Narii, Kyoko Tomita, Shinsaku Togo, Kazuhisa Takahashi, Mitsuhiro Machitani, Masahi Tachibana, Masaaki Ouchi, Nobuyoshi Katagiri, Yasuo Urata, Toshiyoshi Fujiwara, and Hiroyuki Mizuguchi
Molecular Methods&Clinical Development(2016)3, 16001;doi:10.1038/mtm.2016.1, 2016
- ■Fluorescence-guided surgery of a Highl-metastastatic variant of human triple-negative breast cancer targeted with a cancerspecific GFP adenovirus prevents recurrence
Shuya Yano, Kiyoto Takehara, Shinji Miwa, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuo Urata, Shunsuke Kagawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert M.Hoffman
Oncotarget, Advance Publications 2016, 2016
- ■Targeted Photodynamic Virotherapy Armed with a Genetically Encoded Photosensitizer
Kiyoto Takehara, Hiroshi Tazawa, Naohiro Okada, Yuuri Hashimoto, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Kishimoto, Yasuhiro Shiralawa, Nobuhiro Narii, Hiroyuki Mizuguchi, Yasuo Urata, Shunsuke Kagawa, and Toshiyoshi Fujiwara
Molecular Therpy, January2016 Ther;15(1), 2016
- ■Tracking viable circulating tumor cells (CTCs) in the peripheral blood of non-small cell lung cancer patients undergoing definitive radiation therapy: Pilot study results.
Dorsey JF, Kao GD, MacArthur KM, Ju M, Steinmetz D, Wileyto EP, Simone CB 2nd, Hahn SM.
Cancer, 2014 Sep 19. [Epub ahead of print]
- ■Detection of brain tumor cells in the peripheral blood by a telomerase promoter-based assay.
Macarthur KM, Kao GD, Chandrasekaran S, Alonso-Basanta M, Chapman C, Lustig RA, Wileyto EP, Hahn SM, Dorsey JF.
Cancer Res. 2014 Feb 13. [Epub ahead of print]
浦田 泰生, 片桐 伸悦
腫瘍内科 第11巻 第5号別刷 625-630 2013年5月発行科学評論社, May 2013
- ■A novel approach using telomerasa-specific replication-selective adenovirus for detection of circulating tumor cells in breast cancer patients
Seung Jin Kim, Akinori Masaga, Yasuhiro Tamaki, Kenji Akazawa, Fumine Tsukamoto, Jin Sato, Toshiyuki Ozawa, Yukio Tsujino, Shinzaburo Noguchi
Breast Cancer Res Treat DOI 10.1007/s10549-011-1603-2, Feb. 2012
- ■Preclinical Evalution of Telomerase-Specific Oncolytic Virotherapy for Human Bone and Soft Tissue Sarcomas
Tsuyoshi Sasaki, Hiroshi Tazawa, Jo Hasei, Toshiyuki Kunisada, Aki Yoshida, Yuuri Hashimoto, Syuya Yono, Ryosuke Yoshida, Futoshi Uno, Shunsuke Kagawa, Yuki Morimoto, Yasuo Urata, Toshifumi Ozaki, and Toshiyoshi Fujiwara
Clinical Cancer Research, 17(7)April 1,2011, Apr. 2011
- ■In Vivo Biological Purging forLymph Node Metastasis of Human Colorectal Cancer by Telomerase-Specific Oncolytic Virotherapy
Toru Kojima,MD, Yuichi Watanabe,PhD, Yuuri Hashimoto,BS, Shinji Kuroda,MD, Yasumoto Yamasaki,MD, Shuya Yano,MD, Masaaki Ouchi,BS, Hiroshi Tazawa,MD,PhD, Futoshi Uno,MD,PhD, Shunsuke Kagawa,MD,PhD, Satoru Kyo,MD,PhD,
Annals of Surgery Volume251, Number6, June 2010, Jun. 2010
- ■A simple biological imaging system for detecting viable human circulating tumor cell
Toru Kojima, Yuuri Hashimoto, Yuichi Watanabe, Shunsuke Kagawa, Futoshi Uno, Shinji Kuroda, Hiroshi Tazawa, Satiry Kyo, Hiroyuki Mizuguchi, Yasuo Urata, Noriyuki Tanaka, and Toshiyoshi Fujiwara
The Journal of Clinical Investigation, 119(10): 3172-3181, Oct. 2009
- ■In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus
Hiroyuki Kishimoto, Toru Kojima, Yuichi Watanabe, Shunsuke Kagawa, Toshiya Fujiwara, Futoshi Uno, Fuminori Teraishi, Satoru Kyo, Hiroyuki Mizuguchi, Yuuri Hashimoto, Yasuo Urata, Noriaki Tanaka & Toshiyoshi Fujiwara
Nature Medicine, 12(10):1213-1219, Oct. 2006
- ■Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent OBP-401 with docetaxel: Preclinical evaluation of chemovirotherapy
Toshiya Fujiwara, Shunsuke Kagawa, Hiroyuki Kishimoto, Yoshikatsu Endo, Masayoshi Hioki, Yoshihiro Ikeda, Ryo Sakai,Yasuo Urata, Noriaki Tanaka and Toshiyoshi Fujiwara
International Journal of Cancer, 119:432-440, 2006
- ■Visualization of intrathoracically Disseminated Solid Tumor in Mice with Optical Imaging by Telomerase-Specific Amplification of a Transferred Green Fluorescent Protein Gene.
Umeoka T., Kawashima T., Kagawa S., Teraishi F., Taki M., Nishizaki M., Kyo S., Nagai K., Urata Y., Tanaka N., Fujiwara T.
Cancer Research, 64(17):6259-6265, Sep. 2004