alexa Adoptive Immunotherapy Against Malignant Glioma Using Survivinspecific CTLs Expanded by W6/32 Antibody-mediated Artificial Antigenpresenting Cells | OMICS International | Abstract
ISSN: 2157-7013

Journal of Cell Science & Therapy
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Research Article

Adoptive Immunotherapy Against Malignant Glioma Using Survivinspecific CTLs Expanded by W6/32 Antibody-mediated Artificial Antigenpresenting Cells

Xiaoling Lu1,2,3*, Jiaqi Shi4, Qin Yao5, Jian He1, Yuan Zhou6, Hongbo Cai7 and Yongxiang Zhao1,2,3*
1Biological Target Diagnosis & Treatment Center, Guangxi Medical University, Nanning 530021, China
2The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China
3Department of Immunology, Guangxi Medical University, Nanning 530021, China
4Department of Pathology, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
5Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China
6Department of Pharmacology, Hunan Normal University Medical College, Changsha, Hunan 410013, China
7Department of Pathology, University of Pittsburgh, 200 Lothrop St, BST S-450, Pittsburgh, PA 15213, USA
Corresponding Authors : Yongxiang Zhao
Biological Target Diagnosis & treatment Center
Guangxi Medical University, Nanning 530021, China
Tel: +86 771 535 0964
Fax: +86 771 531 2916
E-mail: [email protected]
  Xiaoling Lu
Biological Target Diagnosis & treatment Center
Guangxi Medical University, Nanning 530021, China
Tel: +86 771 535 0964
Fax: +86 771 531 2916
E-mail: [email protected]
Received September 06, 2011; Accepted September 22, 2011; Published September 24, 2011
Citation: Lu X, Shi J, Yao Q, He J, Zhou Y, et al. (2011) Adoptive Immunotherapy Against Malignant Glioma Using Survivin-specific CTLs Expanded by W6/32 Antibody-mediated Artificial Antigen-presenting Cells. J Cell Sci Ther 2:110. doi: 10.4172/2157-7013.1000110
Copyright: © 2011 Lu X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

"Survivin is a bifunctional protein that acts as a suppressor of apoptosis and plays a central role in cell division. The protein is strongly expressed in the most common human neoplasms, has prognostic relevance for some of them and appears to be involved in tumor cell resistance to anticancer agents and ionizing radiation. Recently, survivin has been reported to be abundantly overexpressed in malignant glioma. The present study is a report of a novel approach of targeting malignant glioma with pSurvivin95-104-specific cytotoxic T-lymphocytes (CTLs). pSurvivin95-104-specific CTLs were induced from the peripheral blood lymphocytes (PBLs) of HLA-A2 positive healthy donors by multiple stimulations with W6/32 antibody-mediated artificial antigen-presenting cells (aAPCs) made by coating HLA-A2/pSurvivin95-104 tetramer mediated by W6/32 antibody, anti-CD28 antibody, 4-1BBL and CD83 molecules to cell-sized latex beads. After multiple stimulations and sorting, the expanded CTLs were analyzed for tetramer staining, IFN-γ production, CTL reactivity and adoptive immunotherapy experiments. Tetramer staining assay demonstrated the expanded CTLs specifically bound HLA-A2- pSurvivin95-104 tetramer. The CTLs specifically produced IFN-γ in response to W6/32 antibody-mediated aAPCs and exhibited specific lysis against T2 cells pulsed with the peptide and HLA-A2+ glioma cells expressing pSurvivin95-104, while HLA-A2- glioma cell lines that express survivin could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-HLA class I monoclonal antibody. Intravenous injection of the expanded pSurvivin95-104-specific CTLs into nonobese diabetic– severe combined immunodeficiency (NOD/SCID) mice harboring glioma cells resulted in glioma cells elimination, whereas transfer of control T-cells was ineffective. These results show the expanded CTLs specific for pSurvivin95-104 peptide could be a potential target of specific immunotherapy for HLA-A2 patients with malignant glioma"

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