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

Cytotherapy. 2012 Jul;14(6):733-42. doi: 10.3109/14653249.2012.666633. Epub 2012 Mar 16.

Abstract

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 α2 chain (IL-13Rα2) 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-13Rα2-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 × 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation*
  • Disease Progression
  • Female
  • Glioma / immunology
  • Glioma / prevention & control
  • Glioma / therapy*
  • HLA-A2 Antigen / immunology*
  • HLA-A24 Antigen / immunology*
  • Humans
  • Interleukin-13 Receptor alpha2 Subunit / immunology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Peptides / immunology*
  • Recurrence
  • Vaccination / adverse effects
  • Vaccination / methods
  • Young Adult

Substances

  • Cancer Vaccines
  • HLA-A*02:01 antigen
  • HLA-A*24:02 antigen
  • HLA-A2 Antigen
  • HLA-A24 Antigen
  • Interleukin-13 Receptor alpha2 Subunit
  • Peptides