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A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2015 Jun 11; Vol. 9, pp. 2947-59. Date of Electronic Publication: 2015 Jun 11 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Background: In previous years, immunotoxins have been shown to be a greatly promising therapeutic tool for brain malignancies, such as gliomas. Human mesenchymal stem cells (hMSCs) exhibit tropism to tumor tissue. However, the effect of bispecific immunotoxins in malignant gliomas is still unknown. The aim of this study was to investigate the function of bispecific immunotoxins in human malignant gliomas.<br />Materials and Methods: In the present study, the bispecific immunotoxin VEGF165-ephrin A1-PE38KDEL was established using deoxyribonucleic acid shuffling and cloning techniques. The VEGF165-ephrin A1-PE38KDEL was delivered by hMSCs to mouse malignant gliomas. The effects of the bispecific immunotoxins on glioma-derived blood vessels and vasculogenic mimicry to elucidate the molecular mechanisms underlying the antitumorigenic effects of immunotoxins were examined in vivo.<br />Results: In vitro, transfected hMSCs significantly inhibited the cell viability of gliomas cell lines U87 and U251 in a dose-dependent manner compared with untransfected hMSCs (P<0.01). In vivo, the intratumoral injection of engineered hMSCs was effective at inhibiting tumor growth in a malignant glioma tumor model.<br />Conclusion: The bispecific immunotoxin secreted from hMSCs acts as a novel strategy for improving treatment options for malignant gliomas in the clinic.
- Subjects :
- Animals
Antibody Specificity
Antineoplastic Agents administration & dosage
Antineoplastic Agents immunology
Bone Marrow Transplantation methods
Brain Neoplasms pathology
Drug Delivery Systems
Ephrins administration & dosage
Ephrins adverse effects
Ephrins immunology
Exotoxins administration & dosage
Exotoxins adverse effects
Glioma pathology
Humans
Immunotoxins administration & dosage
Immunotoxins immunology
Injections, Intralesional
Mesenchymal Stem Cell Transplantation methods
Mice
Transfection
Vascular Endothelial Growth Factor A immunology
Vascular Endothelial Growth Factors administration & dosage
Vascular Endothelial Growth Factors adverse effects
Antineoplastic Agents therapeutic use
Blood Vessels drug effects
Blood Vessels pathology
Bone Marrow Cells immunology
Brain Neoplasms drug therapy
Ephrins therapeutic use
Exotoxins therapeutic use
Glioma drug therapy
Immunotoxins therapeutic use
Mesenchymal Stem Cells immunology
Neovascularization, Pathologic pathology
Vascular Endothelial Growth Factors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 26089644
- Full Text :
- https://doi.org/10.2147/DDDT.S79475