title: A novel bispecific immunotoxin delivered by human bone marrow-derived mesenchymal stem cells to target blood vessels and vasculogenic mimicry of malignant gliomas.
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.
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The bispecific immunotoxin secreted from hMSCs acts as a novel strategy for improving treatment options for malignant gliomas in the clinic.
authors.affiliation: National Key Clinic Specialty, Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; Department of Neurosurgery, First Hospital of Lanzhou University, Lanzhou, People's Republic of China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Key Clinic Specialty, Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Sun
authors.affiliation: National Key Clinic Specialty, Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: National Key Clinic Specialty, Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yiquan
authors.initials: Y
authors.lastname: Ke
authors.affiliation: National Key Clinic Specialty, Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Key Clinic Specialty, Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001808:Blood Vessels / Q000187:drug effects* / Q000473:pathology*; D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000379:methods; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D036342:Ephrins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005098:Exotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D015552:Injections, Intralesional; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000473:pathology*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D042442:Vascular Endothelial Growth Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D036342:Ephrins; D005098:Exotoxins; D000922:Immunotoxins; C000604473:VEGF165-ephrin A1-PE38KDEL; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
keywords: VEGF165; bispecific immunotoxin; ephrin A1; human mesenchymal stem cells; malignant glioma