TY - JOUR
T1 - Bone and soft-tissue sarcoma
T2 - A new target for telomerase-specific oncolytic virotherapy
AU - Tazawa, Hiroshi
AU - Hasei, Jou
AU - Yano, Shuuya
AU - Kagawa, Shunsuke
AU - Ozaki, Toshifumi
AU - Fujiwara, Toshiyoshi
N1 - Funding Information:
This study was supported in part by grants from the Ministry of Education, Culture, Sports, Sciences and Technology, Japan (Nos. 22791310, 25462057, and 16K10596 to H. Tazawa; Nos. 23591932 and 15K15193 to S. Kagawa; No. 25293323 to T. Ozaki; and Nos. 25293283, 25670580, 16H05416, and 19H03731 to T. Fujiwara), the Japan Agency for Medical Research and Development (No. 19ck0106285h0003 to T. Fujiwara), and the National Cancer Center Research and Development Fund (No. 23-A-10 to T. Ozaki).
Funding Information:
Funding: This study was supported in part by grants from the Ministry of Education, Culture, Sports, Sciences and Technology, Japan (Nos. 22791310, 25462057, and 16K10596 to H. Tazawa; Nos. 23591932 and 15K15193 to S. Kagawa; No. 25293323 to T. Ozaki; and Nos. 25293283, 25670580, 16H05416, and 19H03731 to T. Fujiwara), the Japan Agency for Medical Research and Development (No. 19ck0106285h0003 to T. Fujiwara), and the National Cancer Center Research and Development Fund (No. 23-A-10 to T. Ozaki).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2
Y1 - 2020/2
N2 - Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.
AB - Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.
KW - Autophagy
KW - GFP
KW - HTERT
KW - Oncolytic adenovirus
KW - P53
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UR - http://www.scopus.com/inward/citedby.url?scp=85079720567&partnerID=8YFLogxK
U2 - 10.3390/cancers12020478
DO - 10.3390/cancers12020478
M3 - Review article
AN - SCOPUS:85079720567
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 2
M1 - 478
ER -
