Heat shock protein vaccines in glioblastoma

Aden P. Haskell-Mendoza, Orin Bloch

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Heat shock proteins (HSPs) are cellular chaperones abundant in mammalian cells, and play an important role in response to stressors such as hyperthermia, hypoxia, and oxidative stress. The peptide-binding property of HSPs, together with their ability to deliver antigens to antigen-presenting cells, makes them a target for modulation in cancer immunotherapy. As a result, an autologous, patient-derived HSP-96 peptide complex vaccine (HSPPC-96) has been leveraged as an active immunotherapy to stimulate innate and adaptive responses in multiple cancers, including glioblastoma (GBM). To date, HSPPC-96 has demonstrated safety and tolerability in phase I and single-arm phase II trials for recurrent and newly diagnosed GBM, while producing robust immune responses as measured by increased leukocyte counts. Compared with historical controls, the single-arm phase II trials of HSPPC-96 for newly diagnosed and recurrent GBM demonstrated increased progression-free survival (PFS) and overall survival (OS), spurring a phase IIb randomized trial of the vaccine in combination with or in comparison with bevacizumab for recurrent GBM. The impact of immune checkpoints on responsiveness to the vaccine has been identified through post hoc analysis of completed clinical trials, and is now the target of a combined approach utilizing HSPPC-96 vaccination with immune checkpoint inhibition in newly diagnosed GBM.

Original languageEnglish (US)
Title of host publicationImmunotherapeutic Strategies for the Treatment of Glioma
PublisherElsevier
Pages39-53
Number of pages15
ISBN (Electronic)9780128197554
DOIs
StatePublished - Jan 1 2021

Keywords

  • Brain tumor
  • Cancer
  • Glioblastoma
  • Glioma
  • Heat shock proteins
  • HSPPC-96
  • Immunotherapy
  • Vaccines

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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