Use of Dentritic Cells Pulsed with HLA-A2-restricted MAGE-A1 Peptide to Generate Cytotoxic T Lymphocytes against Malignant Glioma

This study developed a novel approach of targeting malignant glioma with pMAGE-A1278-286-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-A1278-286 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-A1278-286 (pMAGE-A1278-286 peptide pulsed T2 cells) and U251 (HLA-A2+, MAGE-A1+) at an effector:target ratio of 40:1, and approximately 5% cytolysis against T2pHIV, A172 (HLA-A2-, MAGE-A1+), K562 and T2 cells without being pulsed with peptide at any effector:target ratio.The specific killing activity of the induced CTLs against T2pMAGE-A1278-286 and U251 was much more obvious than in any other control group (P<0.05).The cytotoxic activity against the T2pMAGE-A1278-286 and U251 was significantly eliminated by anti-HLA class Ⅰ mAb W6/32.These results suggest that pMAGE-A1278-286 epitope may serve as a surrogate tumor antigen target of specific immunotherapy for treating HLA-A2 patients with malignant glioma.