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Urokinase-targeted fusion by oncolytic Sendai virus eradicates orthotopic glioblastomas by pronounced synergy with interferon-β gene.
Mol Ther. 2010 Oct; 18(10):1778-86.MT

Abstract

Glioblastoma multiforme (GM), the most frequent primary malignant brain tumor, is highly invasive due to the expression of proteases, including urokinase-type plasminogen activator (uPA). Here, we show the potential of our new and powerful recombinant Sendai virus (rSeV) showing uPA-specific cell-to-cell fusion activity [rSeV/dMFct14 (uPA2), named "BioKnife"] for GM treatment, an effect that was synergistically enhanced by arming BioKnife with the interferon-β (IFN-β) gene. BioKnife killed human GM cell lines efficiently in a uPA-dependent fashion, and this killing was prevented by PA inhibitor-1. Rat gliosarcoma 9L cells expressing both uPA and its functional receptor uPAR (9L-L/R) exhibited high uPA activity on the cellular surface and were highly susceptible to BioKnife. Although parent 9L cells (9L-P) were resistant to BioKnife and to BioKnife expressing IFN-β (BioKnife-IFNβ), cell-cell fusion of 9L-L/R strongly facilitated the expression of IFN-β, and in turn, IFN-β significantly accelerated the fusion activity of BioKnife. A similar synergy was seen in a rat orthotopic brain GM model with 9L-L/R in vivo; therefore, these results suggest that BioKnife-IFNβ may have significant potential to improve the survival of GM patients in a clinical setting.

Authors+Show Affiliations

Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20606645

Citation

Hasegawa, Yuzo, et al. "Urokinase-targeted Fusion By Oncolytic Sendai Virus Eradicates Orthotopic Glioblastomas By Pronounced Synergy With Interferon-β Gene." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 18, no. 10, 2010, pp. 1778-86.
Hasegawa Y, Kinoh H, Iwadate Y, et al. Urokinase-targeted fusion by oncolytic Sendai virus eradicates orthotopic glioblastomas by pronounced synergy with interferon-β gene. Mol Ther. 2010;18(10):1778-86.
Hasegawa, Y., Kinoh, H., Iwadate, Y., Onimaru, M., Ueda, Y., Harada, Y., Saito, S., Furuya, A., Saegusa, T., Morodomi, Y., Hasegawa, M., Saito, S., Aoki, I., Saeki, N., & Yonemitsu, Y. (2010). Urokinase-targeted fusion by oncolytic Sendai virus eradicates orthotopic glioblastomas by pronounced synergy with interferon-β gene. Molecular Therapy : the Journal of the American Society of Gene Therapy, 18(10), 1778-86. https://doi.org/10.1038/mt.2010.138
Hasegawa Y, et al. Urokinase-targeted Fusion By Oncolytic Sendai Virus Eradicates Orthotopic Glioblastomas By Pronounced Synergy With Interferon-β Gene. Mol Ther. 2010;18(10):1778-86. PubMed PMID: 20606645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urokinase-targeted fusion by oncolytic Sendai virus eradicates orthotopic glioblastomas by pronounced synergy with interferon-β gene. AU - Hasegawa,Yuzo, AU - Kinoh,Hiroaki, AU - Iwadate,Yasuo, AU - Onimaru,Mitsuho, AU - Ueda,Yasuji, AU - Harada,Yui, AU - Saito,Satoru, AU - Furuya,Aki, AU - Saegusa,Takashi, AU - Morodomi,Yosuke, AU - Hasegawa,Mamoru, AU - Saito,Shigeyoshi, AU - Aoki,Ichio, AU - Saeki,Naokatsu, AU - Yonemitsu,Yoshikazu, Y1 - 2010/07/06/ PY - 2010/7/8/entrez PY - 2010/7/8/pubmed PY - 2011/1/20/medline SP - 1778 EP - 86 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 18 IS - 10 N2 - Glioblastoma multiforme (GM), the most frequent primary malignant brain tumor, is highly invasive due to the expression of proteases, including urokinase-type plasminogen activator (uPA). Here, we show the potential of our new and powerful recombinant Sendai virus (rSeV) showing uPA-specific cell-to-cell fusion activity [rSeV/dMFct14 (uPA2), named "BioKnife"] for GM treatment, an effect that was synergistically enhanced by arming BioKnife with the interferon-β (IFN-β) gene. BioKnife killed human GM cell lines efficiently in a uPA-dependent fashion, and this killing was prevented by PA inhibitor-1. Rat gliosarcoma 9L cells expressing both uPA and its functional receptor uPAR (9L-L/R) exhibited high uPA activity on the cellular surface and were highly susceptible to BioKnife. Although parent 9L cells (9L-P) were resistant to BioKnife and to BioKnife expressing IFN-β (BioKnife-IFNβ), cell-cell fusion of 9L-L/R strongly facilitated the expression of IFN-β, and in turn, IFN-β significantly accelerated the fusion activity of BioKnife. A similar synergy was seen in a rat orthotopic brain GM model with 9L-L/R in vivo; therefore, these results suggest that BioKnife-IFNβ may have significant potential to improve the survival of GM patients in a clinical setting. SN - 1525-0024 UR - https://www.unboundmedicine.com/medline/citation/20606645/Urokinase_targeted_fusion_by_oncolytic_Sendai_virus_eradicates_orthotopic_glioblastomas_by_pronounced_synergy_with_interferon_β_gene_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(16)30861-9 DB - PRIME DP - Unbound Medicine ER -