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GBM-Targeted oHSV Armed with Matrix Metalloproteinase 9 Enhances Anti-tumor Activity and Animal Survival
- Source :
- Molecular Therapy: Oncolytics, Vol 15, Iss, Pp 214-222 (2019), Molecular Therapy Oncolytics
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- The use of mutant strains of oncolytic herpes simplex virus (oHSV) in early-phase human clinical trials for the treatment of glioblastoma multiforme (GBM) has proven safe, but limited efficacy suggests that more potent vector designs are required for effective GBM therapy. Inadequate vector performance may derive from poor intratumoral vector replication and limited spread to uninfected cells. Vector replication may be impaired by mutagenesis strategies to achieve vector safety, and intratumoral virus spread may be hampered by vector entrapment in the tumor-specific extracellular matrix (ECM) that in GBM is composed primarily of type IV collagen. In this report, we armed our previously described epidermal growth factor receptor (EGFR)vIII-targeted, neuronal microRNA-sensitive oHSV with a matrix metalloproteinase (MMP9) to improve intratumoral vector distribution. We show that vector-expressed MMP9 enhanced therapeutic efficacy and long-term animal survival in a GBM xenograft model. Keywords: matrix metalloproteinase 9 = MMP9, extracellular matrix = ECM, Oncolytic vectors = OVs, Glioblastoma multiforme = GBM, OVs derived from herpes simplex virus = oHSV
- Subjects :
- 0301 basic medicine
Cancer Research
OVs derived from herpes simplex virus = oHSV
Glioblastoma multiforme = GBM
Mutagenesis (molecular biology technique)
extracellular matrix = ECM
Matrix metalloproteinase
MMP9
Oncolytic vectors = OVs
medicine.disease_cause
lcsh:RC254-282
Article
Virus
03 medical and health sciences
0302 clinical medicine
Medicine
Pharmacology (medical)
Vector (molecular biology)
Epidermal growth factor receptor
biology
business.industry
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
Oncolytic virus
030104 developmental biology
Herpes simplex virus
Oncology
030220 oncology & carcinogenesis
matrix metalloproteinase 9 = MMP9
Cancer research
biology.protein
Molecular Medicine
business
Subjects
Details
- Language :
- English
- ISSN :
- 23727705
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy: Oncolytics
- Accession number :
- edsair.doi.dedup.....5a4909ffde8bda39faac2ff2ccb8a843