Induction of cytotoxic T-lymphocytes specific for malignant glioma by HLA dimer-based artificial antigen-presenting cells.
OBJECTIVE
The aim of this study was to investigate the novel approach for targeting malignant glioma.


METHODS
Interleukin-13 receptor alpha2 (IL-13Ralpha2)-specific cytotoxic T-cells (CTLs) were induced from the peripheral blood lymphocytes (PBLs) of human leukocyte antigen (HLA)-A2 positive healthy donors by multiple stimulations with artificial antigen-presenting cells (aAPCs) made by coating HLA-A2-Ig/pIL-13Ralpha2(345-354) dimeric complexes, anti-CD28 antibody, and CD83 molecules to cell-sized latex beads.


RESULTS
The induced CTLs exhibited a specific lysis against T2 cells pulsed with the peptide pIL-13Ralpha2(345-354) and HLA-A2(+) glioma cells expressing IL-13Ralpha2(345-354), while HLA-A2(-) glioma cell lines that express IL-13Ralpha2(345-354) could not be recognized by the CTLs. The peptide-specific activity was inhibited by the anti-HLA class I monoclonal antibody.


CONCLUSIONS
The induced CTLs specific for the IL-13Ralpha2(345-354) peptide could be a potential target of specific immunotherapy for HLA-A2(+) patients with malignant glioma.
Xiaobing
Jiang
J
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. jxb917@126.com
Xiaoling
Lu
L
Ruen
Liu
L
Fangcheng
Zhang
Z
Hongyang
Zhao
Z
D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D015870:Gene Expression; D005910:Glioma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015789:HLA-A2 Antigen / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology; D008863:Microspheres; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D000097802:CD83 Antigen
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D007371:Interferon-gamma; D053663:Interleukin-13 Receptor alpha2 Subunit; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D000097802:CD83 Antigen