4.5 Article

Peptide-pulsed dendritic cell vaccination targeting interleukin-13 receptor α2 chain in recurrent malignant glioma patients with HLA-A*24/A*02 allele

Journal

CYTOTHERAPY
Volume 14, Issue 6, Pages 733-742

Publisher

ELSEVIER SCI LTD
DOI: 10.3109/14653249.2012.666633

Keywords

dendritic cell; interleukin-13 receptor alpha 2 chain; malignant glioma; vaccination

Funding

  1. Japan Society for the Promotion of Science
  2. Nagoya University Hospital
  3. Grants-in-Aid for Scientific Research [23300354] Funding Source: KAKEN

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Background aims. Dendritic cell (DC)-based vaccination targeting tumor-associated antigens is an attractive approach to overcoming the limitations of current treatments for malignant gliomas (MG). Interleukin-13 receptor alpha 2 chain (IL-13R alpha 2) is a promising target because of its abundant and specific expression in MG. We conducted a phase I trial of DC vaccination in patients with recurrent MG using two IL-13R alpha 2-derived peptides restricted to HLA-A*0201 and -A*2402. The objective was to evaluate the safety and clinical and immunologic responses. Methods. Eight recurrent MG patients were enrolled. DC were generated from peripheral blood and pulsed with HLA-matched peptide; 1 x 10(7) DC were administered every 2 weeks for a maximum of six immunizations. The T-cell response in peripheral blood was evaluated by tetramer and ELISPOT assays in HLA-A*2402 patients. Results. All enrolled patients except one completed at least four DC vaccinations. No severe adverse events were observed. A positive T-cell response was detected in two out of three evaluable HLA-A*2402 patients. One patient achieved stable disease for 16 months and another patient showed a dramatic regression for one lesion for 4 months. Conclusions. The regimen was feasible and safe, and the HLA-A*24-restricted peptide exhibited a capacity to induce immune responses. These results warrant further studies to evaluate whether add-on regimens to post-operative chemoradiotherapy delays recurrence in newly diagnosed MG patients.

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