Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma

J Clin Oncol. 2011 Jan 20;29(3):330-6. doi: 10.1200/JCO.2010.30.7744. Epub 2010 Dec 13.


Purpose: A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells (αDC1) loaded with synthetic peptides for glioma-associated antigen (GAA) epitopes and administration of polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in HLA-A2(+) patients with recurrent malignant gliomas. GAAs for these peptides are EphA2, interleukin (IL)-13 receptor-α2, YKL-40, and gp100.

Patients and methods: Twenty-two patients (13 with glioblastoma multiforme [GBM], five with anaplastic astrocytoma [AA], three with anaplastic oligodendroglioma [AO], and one with anaplastic oligoastrocytoma [AOA]) received at least one vaccination, and 19 patients received at least four vaccinations at two αDC1 dose levels (1 × or 3 × 10(7)/dose) at 2-week intervals intranodally. Patients also received twice weekly intramuscular injections of 20 μg/kg poly-ICLC. Patients who demonstrated positive radiologic response or stable disease without major adverse events were allowed to receive booster vaccines. T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays.

Results: The regimen was well-tolerated. The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58% of patients. Peripheral blood samples demonstrated significant upregulation of type 1 cytokines and chemokines, including interferon-α and CXCL10. Nine (four GBM, two AA, two AO, and one AOA) achieved progression-free status lasting at least 12 months. One patient with recurrent GBM demonstrated sustained complete response. IL-12 production levels by αDC1 positively correlated with time to progression.

Conclusion: These data support safety, immunogenicity, and preliminary clinical activity of poly-ICLC-boosted αDC1-based vaccines.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Carboxymethylcellulose Sodium / analogs & derivatives*
  • Carboxymethylcellulose Sodium / therapeutic use
  • Cell Polarity / immunology
  • Dendritic Cells / immunology*
  • Epitopes
  • Female
  • Glioma / drug therapy*
  • Humans
  • Interferon Inducers / therapeutic use*
  • Interleukin-12 / metabolism
  • Male
  • Middle Aged
  • Monitoring, Immunologic
  • Poly I-C / therapeutic use*
  • Polylysine / analogs & derivatives*
  • Polylysine / therapeutic use
  • Proportional Hazards Models
  • Recurrence
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology
  • Vaccines, Subunit / therapeutic use*


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • Interferon Inducers
  • Vaccines, Subunit
  • Interleukin-12
  • Polylysine
  • poly ICLC
  • Carboxymethylcellulose Sodium
  • Poly I-C