TY - JOUR
T1 - Development of a detection system for circulating tumor cells in peripheral blood using a next generation conditionally-replicating adenovirus
AU - Sakurai, Fuminori
AU - Fujiwara, Toshiyoshi
AU - Mizuguchia, Hiroyuki
PY - 2013
Y1 - 2013
N2 - An easy and sensitive detection method for circulating tumor cells (CTC) is expected to be developed because CTC are a promising biomarker for early diagnosis of tumors and prognosis prediction of tumor patients. Our group has already developed a CTC detection method using a conditionally replicating adenovirus (Ad) which efficiently replicates and expresses GFP in telomerase-positive tumor cells. However, malignant tumor cells express much low levels of coxsackievirus and adenovirus receptor (CAR), leading to inefficient infection with a conventional conditionally replicating Ad. In addition, a tiny fraction of normal blood cells, including lymphocytes, express GFP following infection. To overcome these problems, we have developed a next-generation conditionally replicating Ad. The next-generation conditionally replicating Ad possesses the fiber protein derived from Ad serotype 35, leading to efficient infection in both CAR-positive and -negative tumor cells, because the fiber protein of Ad serotype 35 binds to CD46, which is expressed on almost all human cells. Furthermore, sequences complementary to blood cell-specific miRNA (miR-142-3p) were inserted into the 3′ untranslated region of the E1 gene and GFP gene, leading to the suppression of GFP expression in normal blood cells. In this symposium, we will not only introduce the importance of CTC as a biomarker and conventional CTC detection methods but also show our data of the novel CTC detection using the next-generation conditionally replicating Ad.
AB - An easy and sensitive detection method for circulating tumor cells (CTC) is expected to be developed because CTC are a promising biomarker for early diagnosis of tumors and prognosis prediction of tumor patients. Our group has already developed a CTC detection method using a conditionally replicating adenovirus (Ad) which efficiently replicates and expresses GFP in telomerase-positive tumor cells. However, malignant tumor cells express much low levels of coxsackievirus and adenovirus receptor (CAR), leading to inefficient infection with a conventional conditionally replicating Ad. In addition, a tiny fraction of normal blood cells, including lymphocytes, express GFP following infection. To overcome these problems, we have developed a next-generation conditionally replicating Ad. The next-generation conditionally replicating Ad possesses the fiber protein derived from Ad serotype 35, leading to efficient infection in both CAR-positive and -negative tumor cells, because the fiber protein of Ad serotype 35 binds to CD46, which is expressed on almost all human cells. Furthermore, sequences complementary to blood cell-specific miRNA (miR-142-3p) were inserted into the 3′ untranslated region of the E1 gene and GFP gene, leading to the suppression of GFP expression in normal blood cells. In this symposium, we will not only introduce the importance of CTC as a biomarker and conventional CTC detection methods but also show our data of the novel CTC detection using the next-generation conditionally replicating Ad.
KW - CD46
KW - Circulating tumor cell
KW - Conditional replication-competent adenovirus
KW - Fiber
KW - MiRNA
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UR - http://www.scopus.com/inward/citedby.url?scp=84946165166&partnerID=8YFLogxK
U2 - 10.1248/yakushi.12-00237-1
DO - 10.1248/yakushi.12-00237-1
M3 - Review article
AN - SCOPUS:84946165166
VL - 133
SP - 291
EP - 296
JO - Yakugaku Zasshi
JF - Yakugaku Zasshi
SN - 0031-6903
IS - 3
ER -