Article

Individual Patient-Specific Immunity against High-Grade Glioma after Vaccination with Autologous Tumor Derived Peptides Bound to the 96 KD Chaperone Protein

neurosurgery, UCSF.
Clinical Cancer Research (Impact Factor: 8.72). 08/2012; 19(1). DOI: 10.1158/1078-0432.CCR-11-3358
Source: PubMed

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 CD56 IFNγ 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.

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    • "HSPs are known to bind receptors expressed by DCs resulting in CD4 and CD8 T-cell responses. Crane and coworkers investigated HSP96 for use as a cancer vaccine[62]. Twelve patients with recurrent glioblastoma were treated with tumor-derived HSP peptide complex consisting of HSP96 and a broad array of tumor-associated antigenic peptides. "
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    • "HSP-96 from GBM has been investigated by Crane et al. [67] for use as a cancer vaccine. Twelve patients with recurrent GBM were treated in this phase I study with intradermal injections of autologous tumor-derived HSP peptide complex (HSPPC), a complex consisting of HSP-96 and a broad array of tumor-associated antigenic peptides. "
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