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Enhancing dendritic cell-based vaccination for highly aggressive glioblastoma

Expert Opin Biol Ther. 2015 Jan;15(1):79-94. doi: 10.1517/14712598.2015.972361. Epub 2014 Oct 18.

Abstract

Introduction: Patients with primary glioblastoma (GBM) have a dismal prognosis despite standard therapy, which can induce potentially deleterious side effects. Arming the immune system is an alternative therapeutic approach, as its cellular effectors and inherent capacity for memory can be utilized to specifically target invasive tumor cells, while sparing collateral damage to otherwise healthy brain parenchyma.

Areas covered: Active immunotherapy is aimed at eliciting a specific immune response against tumor antigens. Dendritic cells (DCs) are one of the most potent activators of de novo and recall immune responses and are thus a vehicle for successful immunotherapy. Currently, investigators are optimizing DC vaccines by enhancing maturation status and migratory potential to induce more potent antitumor responses. An update on the most recent DC immunotherapy trials is provided.

Expert opinion: Targeting of unique antigens restricted to the tumor itself is the most important parameter in advancing DC vaccines. In order to overcome intrinsic mechanisms of immune evasion observed in GBM, the future of DC-based therapy lies in a multi-antigenic vaccine approach. Successful targeting of multiple antigens will require a comprehensive understanding of all immunologically relevant oncological epitopes present in each tumor, thereby permitting a rational vaccine design.

Keywords: EGFR variant III; antigen escape; dendritic cell; glioblastoma; immunotherapy; tumor-specific antigen.

Publication types

  • Review

MeSH terms

  • Antigens, Neoplasm / immunology
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cancer Vaccines / therapeutic use*
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Epitopes / immunology
  • Glioblastoma / immunology
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasm Invasiveness
  • Tumor Escape

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes