Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus
Circulating tumor cells (CTCs) are promising biomarkers in several cancers, and thus methods and apparatuses for their detection and quantification in the blood have been actively pursued. A novel CTC detection system using a green fluorescence protein (GFP)–expressing conditionally replicating aden...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-01-01
|
| Series: | Molecular Therapy: Methods & Clinical Development |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050116301504 |
| _version_ | 1818007405207748608 |
|---|---|
| author | Fuminori Sakurai Nobuhiro Narii Kyoko Tomita Shinsaku Togo Kazuhisa Takahashi Mitsuhiro Machitani Masashi Tachibana Masaaki Ouchi Nobuyoshi Katagiri Yasuo Urata Toshiyoshi Fujiwara Hiroyuki Mizuguchi |
| author_facet | Fuminori Sakurai Nobuhiro Narii Kyoko Tomita Shinsaku Togo Kazuhisa Takahashi Mitsuhiro Machitani Masashi Tachibana Masaaki Ouchi Nobuyoshi Katagiri Yasuo Urata Toshiyoshi Fujiwara Hiroyuki Mizuguchi |
| author_sort | Fuminori Sakurai |
| collection | DOAJ |
| description | Circulating tumor cells (CTCs) are promising biomarkers in several cancers, and thus methods and apparatuses for their detection and quantification in the blood have been actively pursued. A novel CTC detection system using a green fluorescence protein (GFP)–expressing conditionally replicating adenovirus (Ad) (rAd-GFP) was recently developed; however, there is concern about the production of false-positive cells (GFP-positive normal blood cells) when using rAd-GFP, particularly at high titers. In addition, CTCs lacking or expressing low levels of coxsackievirus–adenovirus receptor (CAR) cannot be detected by rAd-GFP, because rAd-GFP is constructed based on Ad serotype 5, which recognizes CAR. In order to suppress the production of false-positive cells, sequences perfectly complementary to blood cell–specific microRNA, miR-142-3p, were incorporated into the 3′-untranslated region of the E1B and GFP genes. In addition, the fiber protein was replaced with that of Ad serotype 35, which recognizes human CD46, creating rAdF35-142T-GFP. rAdF35-142T-GFP efficiently labeled not only CAR-positive tumor cells but also CAR-negative tumor cells with GFP. The numbers of false-positive cells were dramatically lower for rAdF35-142T-GFP than for rAd-GFP. CTCs in the blood of cancer patients were detected by rAdF35-142T-GFP with a large reduction in false-positive cells. |
| first_indexed | 2024-04-14T05:16:13Z |
| format | Article |
| id | doaj.art-128b7af350774539b556453cc3658afa |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-04-14T05:16:13Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-128b7af350774539b556453cc3658afa2022-12-22T02:10:22ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012016-01-013C10.1038/mtm.2016.1Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirusFuminori Sakurai0Nobuhiro Narii1Kyoko Tomita2Shinsaku Togo3Kazuhisa Takahashi4Mitsuhiro Machitani5Masashi Tachibana6Masaaki Ouchi7Nobuyoshi Katagiri8Yasuo Urata9Toshiyoshi Fujiwara10Hiroyuki Mizuguchi11Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanDivision of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine, Tokyo, JapanDivision of Respiratory Medicine, Juntendo University Faculty of Medicine & Graduate School of Medicine, Tokyo, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanOncolys Biopharma, Tokyo, JapanOncolys Biopharma, Tokyo, JapanOncolys Biopharma, Tokyo, JapanDepartment of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanCirculating tumor cells (CTCs) are promising biomarkers in several cancers, and thus methods and apparatuses for their detection and quantification in the blood have been actively pursued. A novel CTC detection system using a green fluorescence protein (GFP)–expressing conditionally replicating adenovirus (Ad) (rAd-GFP) was recently developed; however, there is concern about the production of false-positive cells (GFP-positive normal blood cells) when using rAd-GFP, particularly at high titers. In addition, CTCs lacking or expressing low levels of coxsackievirus–adenovirus receptor (CAR) cannot be detected by rAd-GFP, because rAd-GFP is constructed based on Ad serotype 5, which recognizes CAR. In order to suppress the production of false-positive cells, sequences perfectly complementary to blood cell–specific microRNA, miR-142-3p, were incorporated into the 3′-untranslated region of the E1B and GFP genes. In addition, the fiber protein was replaced with that of Ad serotype 35, which recognizes human CD46, creating rAdF35-142T-GFP. rAdF35-142T-GFP efficiently labeled not only CAR-positive tumor cells but also CAR-negative tumor cells with GFP. The numbers of false-positive cells were dramatically lower for rAdF35-142T-GFP than for rAd-GFP. CTCs in the blood of cancer patients were detected by rAdF35-142T-GFP with a large reduction in false-positive cells.http://www.sciencedirect.com/science/article/pii/S2329050116301504 |
| spellingShingle | Fuminori Sakurai Nobuhiro Narii Kyoko Tomita Shinsaku Togo Kazuhisa Takahashi Mitsuhiro Machitani Masashi Tachibana Masaaki Ouchi Nobuyoshi Katagiri Yasuo Urata Toshiyoshi Fujiwara Hiroyuki Mizuguchi Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus Molecular Therapy: Methods & Clinical Development |
| title | Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus |
| title_full | Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus |
| title_fullStr | Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus |
| title_full_unstemmed | Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus |
| title_short | Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus |
| title_sort | efficient detection of human circulating tumor cells without significant production of false positive cells by a novel conditionally replicating adenovirus |
| url | http://www.sciencedirect.com/science/article/pii/S2329050116301504 |
| work_keys_str_mv | AT fuminorisakurai efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT nobuhironarii efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT kyokotomita efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT shinsakutogo efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT kazuhisatakahashi efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT mitsuhiromachitani efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT masashitachibana efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT masaakiouchi efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT nobuyoshikatagiri efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT yasuourata efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT toshiyoshifujiwara efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus AT hiroyukimizuguchi efficientdetectionofhumancirculatingtumorcellswithoutsignificantproductionoffalsepositivecellsbyanovelconditionallyreplicatingadenovirus |