title: Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma.
abstract: BACKGROUND
  This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107).
  
  
  METHODS
  TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma (GBM) were eligible. Mononuclear cells from leukapheresis were differentiated into dendritic cells, pulsed with TAA peptides, and administered intradermally three times at two-week intervals.
  
  
  RESULTS
  Twenty-one patients were enrolled with 17 newly diagnosed (ND-GBM) and three recurrent GBM patients and one brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33 % responders. TAA expression by qRT-PCR from fresh-frozen tumor samples showed all patient tumors expressed at least three TAA, with 75 % expressing all six. Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM-2 were observed, and a trend for longer survival was observed with gp100 and HER2 antigens. Target antigens gp100, HER1, and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2+ patients. A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection. At a median follow-up of 40.1 months, six of 16 ND-GBM patients showed no evidence of tumor recurrence. Median PFS in newly diagnosed patients was 16.9 months, and median OS was 38.4 months.
  
  
  CONCLUSIONS
  Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors.
authors: Neuro-Oncology Program, Department of Neurosurgery and Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. phuphanich@cshs.org
authors: Surasak
authors: S
authors: Phuphanich
authors: Christopher J
authors: CJ
authors: Wheeler
authors: Jeremy D
authors: JD
authors: Rudnick
authors: Mia
authors: M
authors: Mazer
authors: Hongqian
authors: H
authors: Wang
authors: Miriam A
authors: MA
authors: Nuño
authors: Jaime E
authors: JE
authors: Richardson
authors: Xuemo
authors: X
authors: Fan
authors: Jianfei
authors: J
authors: Ji
authors: Ray M
authors: RM
authors: Chu
authors: James G
authors: JG
authors: Bender
authors: Elma S
authors: ES
authors: Hawkins
authors: Chirag G
authors: CG
authors: Patil
authors: Keith L
authors: KL
authors: Black
authors: John S
authors: JS
authors: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005909:Glioblastoma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D015395:Histocompatibility Antigens Class I