Possible novel therapy for malignant gliomas with secretable trimeric TRAIL

Moonsup Jeong, Yong Sam Kwon, Soon Hye Park, Chae Young Kim, Sin Soo Jeun, Kang Won Song, Yong Ko, Paul D. Robbins, Timothy R. Billiar, Byong Moon Kim, Dai Wu Seol

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inclucing ligand (TRAIL) has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL) and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL) delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI). Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas. Copyright:

Original languageEnglish (US)
Article numbere4545
JournalPloS one
Volume4
Issue number2
DOIs
StatePublished - Feb 20 2009
Externally publishedYes

Fingerprint Dive into the research topics of 'Possible novel therapy for malignant gliomas with secretable trimeric TRAIL'. Together they form a unique fingerprint.

Cite this