CpG oligonucleotides as cancer vaccine adjuvants

Hidekazu Shirota, Debra Tross, Dennis M. Klinman

Research output: Contribution to journalReview articlepeer-review

62 Citations (Scopus)

Abstract

Adjuvants improve host responsiveness to co-delivered vaccines through a variety of mechanisms. Agents that trigger cells expressing Toll-like receptors (TLR) activate an innate immune response that enhances the induction of vaccine-specific immunity. When administered in combination with vaccines designed to prevent or slow tumor growth, TLR agonists have significantly improved the generation of cytotoxic T lymphocytes. Unfortunately, vaccines containing TLR agonists have rarely been able to eliminate large established tumors when administered systemically. To improve efficacy, attention has focused on delivering TLR agonists intra-tumorally with the intent of altering the tumor microenvironment. Agonists targeting TLRs 7/8 or 9 can reduce the frequency of Tregs while causing immunosuppressive MDSC in the tumor bed to differentiate into tumoricidal macrophages thereby enhancing tumor elimination. This work reviews pre-clinical and clinical studies concerning the utility of TLR 7/8/9 agonists as adjuvants for tumor vaccines.

Original languageEnglish
Pages (from-to)390-407
Number of pages18
JournalVaccines
Volume3
Issue number2
DOIs
Publication statusPublished - 2015 May 8

Keywords

  • Cancer
  • CpG
  • TLR
  • Vaccine

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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