Induction of cytotoxic T-lymphocytes specific for malignant glioma by HLA dimer-based artificial antigen-presenting cells.

Aim: 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.