CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity

Hidekazu Shirota, Dennis M. Klinman

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

The primary goal of cancer immunotherapy is to elicit an immune response capable of eradicating established tumors and preventing tumor metastasis. One strategy to achieve this goal utilizes whole killed tumor cells as the primary immunogen. Killed tumor cells provide a comprehensive source of tumor-associated antigens (TAAs), thereby eliminating the need to identify individual antigens. Unfortunately, killed tumor cells tend to be poorly immunogenic. To overcome this limitation, we covalently conjugated immunostimulatory CpG oligodeoxynucleotides (ODN) to apoptotic tumor cells and examined their ability to induce TAA-specific immune responses. Results indicate that CpG conjugation enhances the uptake of cell-based vaccines by dendritic cells (DCs), up-regulates co-stimulatory molecule expression, and promotes the production of immunostimulatory cytokines. Vaccination with CpG-conjugated tumor cells triggers the expansion of tumor-specific cytotoxic T lymphocytes (CTL) that reduce the growth of established tumors and prevents their metastatic spread. Thus, conjugating CpG ODN to cell-based tumor vaccines is an important step toward improving cancer immunotherapy.

Original languageEnglish
Pages (from-to)659-669
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume60
Issue number5
DOIs
Publication statusPublished - 2011 May
Externally publishedYes

Keywords

  • Adjuvant
  • Cancer
  • CpG ODN
  • TLR9
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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