Use of dentritic cells pulsed with HLA-A2-restricted MAGE-A1 peptide to generate cytotoxic T lymphocytes against malignant glioma / 华中科技大学学报（医学）（英德文版）

ABSTRACT

This study developed a novel approach of targeting malignant glioma with pMAGE-A1(278-286)-specific cytotoxic T lymphocytes (CTLs) induced from the peripheral blood mononuclear cells of healthy donors by multiple stimulations with human leukocyte antigen (HLA)-A2-restricted pMAGE-A1(278-286) peptide-pulsed dentritic cells. Cytotoxic assays were performed by the colorimetric CytoTox 96 assay to analyze cytotoxic activity of the induced CTLs against various target cells. The induced CTLs showed approximately 45% specific lysis against T2pMAGE-A1(278-286) (pMAGE-A1(278-286) peptide pulsed T2 cells) and U251 (HLA-A2(+), MAGE-A1(+)) at an effectortarget ratio of 401, and approximately 5% cytolysis against T2pHIV, A172 (HLA-A2(-), MAGE-A1(+)), K562 and T2 cells without being pulsed with peptide at any effectortarget ratio. The specific killing activity of the induced CTLs against T2pMAGE-A1(278-286) and U251 was much more obvious than in any other control group (P<0.05). The cytotoxic activity against the T2pMAGE-A1(278-286) and U251 was significantly eliminated by anti-HLA class I mAb W6/32. These results suggest that pMAGE-A1(278-286) epitope may serve as a surrogate tumor antigen target of specific immunotherapy for treating HLA-A2 patients with malignant glioma.