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An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme.

Publication ,  Journal Article
Sampson, JH; Archer, GE; Mitchell, DA; Heimberger, AB; Herndon, JE; Lally-Goss, D; McGehee-Norman, S; Paolino, A; Reardon, DA; Friedman, AH ...
Published in: Mol Cancer Ther
October 2009

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent and tumor-specific mutation widely expressed in GBMs and other neoplasms. The safety and immunogenicity of a dendritic cell (DC)-based vaccine targeting the EGFRvIII antigen was evaluated in this study. Adults with newly diagnosed GBM, who had undergone gross-total resection and standard conformal external beam radiotherapy, received three consecutive intradermal vaccinations with autologous mature DCs pulsed with an EGFRvIII-specific peptide conjugated to keyhole limpet hemocyanin. The dose of DCs was escalated in cohorts of three patients. Patients were monitored for toxicity, immune response, radiographic and clinical progression, and death. No allergic reactions or serious adverse events were seen. Adverse events were limited to grade 2 toxicities. The maximum feasible dose of antigen-pulsed mature DCs was reached at 5.7 x 10(7) +/- 2.9 x 10(7) SD without dose-limiting toxicity. EGFRvIII-specific immune responses were evident in most patients. The mean time from histologic diagnosis to vaccination was 3.6 +/- 0.6 SD months. Median time to progression from vaccination was 6.8 months [95% confidence interval (C.I.(95)), 2.5-8.8], and median survival time from vaccination was 18.7 months (C.I.(95), 14.5-25.6). Overall median survival from time of histologic diagnosis was 22.8 months (C.I.(95), 17.5-29). This study establishes the EGFRvIII mutation as a safe and immunogenic tumor-specific target for immunotherapy.

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Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

October 2009

Volume

8

Issue

10

Start / End Page

2773 / 2779

Location

United States

Related Subject Headings

  • Survival Analysis
  • Oncology & Carcinogenesis
  • Mutant Proteins
  • Middle Aged
  • Male
  • Immunity
  • Humans
  • Glioblastoma
  • Female
  • ErbB Receptors
 

Citation

APA
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MLA
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Sampson, J. H., Archer, G. E., Mitchell, D. A., Heimberger, A. B., Herndon, J. E., Lally-Goss, D., … Bigner, D. D. (2009). An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther, 8(10), 2773–2779. https://doi.org/10.1158/1535-7163.MCT-09-0124
Sampson, John H., Gary E. Archer, Duane A. Mitchell, Amy B. Heimberger, James E. Herndon, Denise Lally-Goss, Sharon McGehee-Norman, et al. “An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme.Mol Cancer Ther 8, no. 10 (October 2009): 2773–79. https://doi.org/10.1158/1535-7163.MCT-09-0124.
Sampson JH, Archer GE, Mitchell DA, Heimberger AB, Herndon JE, Lally-Goss D, et al. An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther. 2009 Oct;8(10):2773–9.
Sampson, John H., et al. “An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme.Mol Cancer Ther, vol. 8, no. 10, Oct. 2009, pp. 2773–79. Pubmed, doi:10.1158/1535-7163.MCT-09-0124.
Sampson JH, Archer GE, Mitchell DA, Heimberger AB, Herndon JE, Lally-Goss D, McGehee-Norman S, Paolino A, Reardon DA, Friedman AH, Friedman HS, Bigner DD. An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther. 2009 Oct;8(10):2773–2779.

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

October 2009

Volume

8

Issue

10

Start / End Page

2773 / 2779

Location

United States

Related Subject Headings

  • Survival Analysis
  • Oncology & Carcinogenesis
  • Mutant Proteins
  • Middle Aged
  • Male
  • Immunity
  • Humans
  • Glioblastoma
  • Female
  • ErbB Receptors