Individual patient-specific immunity against high-grade glioma after vaccination with autologous tumor derived peptides bound to the 96 KD chaperone protein

Courtney A. Crane, Seunggu (Jude) Han, Brian Ahn, Jessica Oehlke, Valerie Kivett, Anne Fedoroff, Nicholas Butowski, Susan M. Chang, Jennifer Clarke, Mitchel S. Berger, Michael W. McDermott, Michael D. Prados, Andrew T. Parsa

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Purpose: Cancer immunotherapy offers hope of a highly specific nontoxic adjuvant treatment. Heat shock protein peptide complexes (HSPPCs) found in cancer cells carry tumor-specific antigenic proteins and can facilitate adaptive and innate immune responses. Here we show that peptides bound to a 96 kD chaperone protein (HSP-96) from brain tissue containing glioblastoma multiforme (GBM) can be used to safely immunize patients with recurrent GBM. Experimental Design: Multimodality immunomonitoring was completed on 12 patients with recurrent GBM before and after immunization with an autologous HSPPC vaccine derived from surgically resected tumor. Clinical endpoints included safety assessments and overall survival. Results: No adverse events attributable to the vaccine were found. Testing of peripheral blood leukocytes before and after vaccination revealed a significant peripheral immune response specific for the peptides bound to HSP-96, in 11 of the 12 patients treated. Brain biopsies of immune responders after vaccination revealed focal CD4, CD8, and CD56IFNg positive cell infiltrates, consistent with tumor site specific immune responses. Immune responders had a median survival of 47 weeks after surgery and vaccination, compared with 16 weeks for the single nonresponder. Conclusions: These data provide the first evidence in humans of individual patient-specific immune responses against autologous tumor derived peptides bound to HSP-96.

Original languageEnglish (US)
Pages (from-to)205-214
Number of pages10
JournalClinical Cancer Research
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 1 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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