Gene Therapy of Intracranial Glioma Using Interleukin 12-Secreting Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells
SCIE
SCOPUS
- Title
- Gene Therapy of Intracranial Glioma Using Interleukin 12-Secreting Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells
- Authors
- Ryu, CH; Park, SH; Park, SA; Kim, SM; Lim, JY; Jeong, CH; Yoon, WS; Oh, WI; Sung, YC; Jeun, SS
- Date Issued
- 2011-06
- Publisher
- MARY ANN LIEBERT INC
- Abstract
- Clinical trials of gene therapy using a viral delivery system for glioma have been limited. Recently, gene therapy using stem cells as the vehicles for delivery of therapeutic agents has emerged as a new treatment strategy for malignant brain tumors. In this study, we used human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) as delivery vehicles with glioma-targeting capabilities, and modified interleukin-12 (IL-12p40N220Q; IL-12M) as a novel therapeutic gene. We also engineered UCB-MSCs to secret IL-12M(UCB-MSC-IL12M) via tetrameric cell-permeable peptide (4HP4)-mediated adenoviral transduction. We confirmed the migratory capacity of UCB-MSC-IL12M toward GL26 mouse glioma cells by an in vitro migration assay and in vivo injection of UCB-MSC-IL12M into the ipsilateral hemisphere of implanted gliomas in C57BL/6 mice. In vivo efficacy experiments showed that intratumoral injection of UCB-MSC-IL12M significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with control mice. Antitumor effects were associated with increased local IL-12M levels, followed by interferon-g secretion and T-cell infiltration in intracranial gliomas, as well as antiangiogenesis. Interestingly, tumor-free mice after UCB-MSC-IL12M treatment were resistant to ipsilateral and contralateral tumor rechallenge, which was closely associated with tumor-specific long-term T-cell immunity. Thus, our results provide the rationale for designing novel experimental protocols to induce long-term antitumor immunity against intracranial gliomas using UCB-MSCs as an effective delivery vehicle for therapeutic cytokines including IL-12M.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/10220
- DOI
- 10.1089/HUM.2010.187
- ISSN
- 1043-0342
- Article Type
- Article
- Citation
- HUMAN GENE THERAPY, vol. 22, no. 6, page. 733 - 743, 2011-06
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