title: Peptide-pulsed dendritic cell vaccination targeting interleukin-13 receptor α2 chain in recurrent malignant glioma patients with HLA-A*24/A*02 allele.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Iwami
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimato
authors.forename: Masasuke
authors.initials: M
authors.lastname: Ohno
authors.forename: Hideho
authors.initials: H
authors.lastname: Okada
authors.forename: Norimoto
authors.initials: N
authors.lastname: Nakahara
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Sato
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D015789:HLA-A2 Antigen / Q000276:immunology*; D059871:HLA-A24 Antigen / Q000276:immunology*; D006801:Humans; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology*; D012008:Recurrence; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; C435939:HLA-A*02:01 antigen; C438506:HLA-A*24:02 antigen; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D053663:Interleukin-13 Receptor alpha2 Subunit; D010455:Peptides