The evolution of the EGFRvIII (rindopepimut) immunotherapy for glioblastoma multiforme patients

Hum Vaccin Immunother. 2014;10(11):3322-31. doi: 10.4161/21645515.2014.983002.

Abstract

Glioblastoma Multiforme (GBM) is the most common type of brain tumor and it is uniformly fatal. The community standard of treatment for this disease is gross or subtotal resection of the tumor, followed by radiation and temozolomide. At recurrence bevacizumab can be added for increased progression free survival. Many challenges are encountered while trying to devise new drugs to treat GBM, such as the presence of the blood brain barrier which is impermeable to most drugs. Therefore in the past few years attention was turned to immunological means for the treatment of this devastating disease. EGFRvIII targeting has proven a good way to attack glioblastoma cells by using the immune system. Although in still in development, this approach holds the promise as a great first step toward immune-tailored drugs for the treatment of brain cancers.

Keywords: ACTIVATE, A Complementary Trial of an Immunotherapy Vaccine against Tumor Specific EGRFvIII; APC, antigen-presenting cell; Ab, antibody; BBB, blood brain barrier; CD25, cluster of differentiation 25; CD4, cluster of differentiation 4; CNS, central nervous system; CPT-11, irinotecan, Camptosar; CTL, Cytotoxic T lymphocytes; D, day; DTH, delayed-type hypersensitivity; EGFRVIII; EGFRvIII, The epidermal growth factor receptor variant III; EORTC, European Organization for Research and Treatment of Cancer; GAGE, G antigen gene family; GBM, Glioblastoma Multiforme; GM-CSF, Granulocyte-macrophage colony-stimulating factor; Grb2, Growth factor receptor-bound protein 2; HLA, human leukocyte antigen; IL-10, Interleukin-10; IL-12, Interleukin-12; IL-2, Interleukin-2; INF-g, Interferon gamma; KLH, keyhole limpet hemocyanin; KPS, Karnofsky performance status; LPS, lipopolysaccharide; MGMT, O-6-methylguanine-DNA methyltransferase; MHC, major histocompatibility complex; NCIC, National Cancer Institute of Canada; OS, overall survival; PFS, progression-free survival; PGE2, prostaglandin E2; Ras, rat sarcoma genes; SEER, Surveillance, Epidemiology, and End Results Program; TGF-b, transforming growth factor beta; TH2 cells, T helper type 2 cells; TMZ, temozolomide; TTP, time to progression; Treg cells, regulatory T cells; VEGF, Vascular endothelial growth factor; WHO, World Health Organization; Y, year; brain; glioblastoma; therapies; vaccine.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Blood-Brain Barrier
  • Brain Neoplasms / immunology
  • Brain Neoplasms / therapy*
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Chemoradiotherapy
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / immunology*
  • Glioblastoma / immunology
  • Glioblastoma / therapy*
  • Humans
  • Immunotherapy
  • Irinotecan
  • Mice
  • Temozolomide
  • Vaccination
  • Vaccines, Subunit / immunology
  • Vaccines, Subunit / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Cancer Vaccines
  • Vaccines, Subunit
  • epidermal growth factor receptor VIII
  • Bevacizumab
  • Irinotecan
  • Dacarbazine
  • EGFR protein, human
  • ErbB Receptors
  • rindopepimut
  • Camptothecin
  • Temozolomide