Tumor-specific peptide vaccination in newly-diagnosed patients with GBM.

Published

Journal Article

2529 Background: Despite multimodality approaches, survival with GBM is dismal. Induction of immune responses to suppress the infiltrative, residual component with an easily manufactured and administered immunotherapy has been a theoretical ideal. The epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific cell surface protein expressed on approximately 40% of GBMs. METHODS: Newly-diagnosed GBM patients with a gross-total resection, a KPS ≥70, and EGFRvIII+, after undergoing radiation with concurrent temozolomide without tumor progression, were eligible to receive EGFRvIII peptide vaccination i.d. with GM-CSF. Primary endpoint was safety. RESULTS: Accrual began in 06/14/2004 and is now complete. 19 patients were enrolled. Median follow-up is 18 months. Toxicity was minimal and without evidence of autoimmunity. Humoral and cellular immune responses were generated. Median TTP from surgery in vaccine-treated patients is 12 months (n = 12), comparing favorably with a historical matched unvaccinated cohort (gross total resection without progression during radiation, KPS≥70, EGFRvIII+) that had a median TTP of 7.1 months (n = 39) (p = 0.0058). These results also compared favorably with those reported for concurrent temozolomide and radiation followed by adjuvant temozolomide, with a median TTP of 6.9 months. Median survival in this trial has exceeded 18 months which compares favorably to all published analyses accounting for all known prognostic indicators. Among recurrent tumors evaluated by immunohistochemistry, 100% no longer expressed the EGFRvIII, suggesting immunological activation that eliminated EGFRvIII-expressing cells, as well as one potential mechanism of treatment failure. CONCLUSIONS: EGFRvIII peptide vaccination warrants further investigation in a larger randomized clinical trial in patients with EGFRvIII-expressing tumors. No significant financial relationships to disclose.

Full Text

Duke Authors

Cited Authors

  • Heimberger, AB; Hussain, SF; Aldape, K; Sawaya, R; Archer, GA; Friedman, H; Reardon, D; Friedman, A; Bigner, D; Sampson, JH

Published Date

  • June 20, 2006

Published In

Volume / Issue

  • 24 / 18_suppl

Start / End Page

  • 2529 -

PubMed ID

  • 27955024

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Language

  • eng

Conference Location

  • United States