A characterization of dendritic cells and their role in immunotherapy in glioblastoma: From preclinical studies to clinical trials

Siddhartha Srivastava, Christina Jackson, Timothy Kim, John Choi, Michael Lim

Research output: Contribution to journalArticle

Abstract

Glioblastoma (GBM) is themost common and fatal primary central nervous systemmalignancy in adults with a median survival of less than 15 months. Surgery, radiation, and chemotherapy are the standard of care and provide modest benefits in survival, but tumor recurrence is inevitable. The poor prognosis of GBMhas made the development of novel therapies targeting GBMof paramount importance. Immunotherapy via dendritic cells (DCs) has garnered attention and research as a potential strategy to boost anti-tumor immunity in recent years. As the “professional” antigen processing and presenting cells, DCs play a key role in the initiation of anti-tumor immune responses. Pre-clinical studies in GBM have shown long-term tumor survival and immunological memory in murine models with stimulation of DC activity with various antigens and costimulatory molecules. Phase I and II clinical trials of DC vaccines in GBMhave demonstrated some efficacy in improving the median overall survival withminimal to no toxicity with promising initial results fromthe first Phase III trial. However, there remains no standardization of vaccines in terms of which antigens are used to pulse DCs ex vivo, sites of DC injection, and optimal adjuvant therapies. Future work with DC vaccines aims to elucidate the efficacy of DC-based therapy alone or in combination with other immunotherapy adjuvants in additional Phase III trials.

Original languageEnglish (US)
Article number537
JournalCancers
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2019

Keywords

  • Checkpoint inhibition
  • Clinical trial
  • Combination therapy
  • Dendritic cells
  • Glioblastoma
  • Immunotherapy
  • Myeloid
  • Plasmacytoid
  • Vaccine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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