Therapeutic administration of a synthetic CpG oligodeoxynucleotide triggers formation of anti-CpG antibodies

Cancer Res. 2012 Sep 1;72(17):4304-10. doi: 10.1158/0008-5472.CAN-12-0257. Epub 2012 Jun 27.

Abstract

The synthetic oligodeoxynucleotide CpG 7909, which contains unmethylated cytosine/guanine (CpG) motifs, has potent immunostimulatory effects when coadministered with NY-ESO-1 peptides or recombinant NY-ESO-1 protein, resulting in an enhanced cellular and humoral immune response against the vaccine antigen. In this study, we report the development of anti-CpG-ODN antibodies in 21 of 37 patients who received CpG 7909 either alone or as a vaccine adjuvant. Specific anti-CpG immunoglobulin G (IgG) antibody titers ranged from 1:400 to 1:100,000. The anti-CpG antibodies cross-reacted with other synthetic CpG-ODNs but not with the DNA of mixed bacterial vaccine and were shown to be phosphorothioate backbone specific. Vaccine-related severe side effects observed in some patients were most likely not related to the development of anti-CpG antibodies. In addition, anti-CpG antibodies did not have negative effects on the vaccine immune response. These results show that anti-CpG antibodies develop in humans against short unmethylated CpG dinucleotide sequences after administration of CpG 7909. Our data therefore substantiate the potency of CpG 7909 to directly stimulate human B-cells and suggest that anti-CpG antibody monitoring should be a part of ongoing and planned clinical trials with CpG-ODNs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects
  • Antibodies / immunology*
  • Antibody Specificity / immunology
  • Antigen-Antibody Complex / blood
  • Antigen-Antibody Complex / immunology
  • Antigens, Neoplasm / therapeutic use
  • Cancer Vaccines
  • Humans
  • Immunoglobulin G / immunology
  • Membrane Proteins / therapeutic use
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Oligodeoxyribonucleotides / administration & dosage*
  • Oligodeoxyribonucleotides / adverse effects
  • Oligodeoxyribonucleotides / immunology*
  • Vaccines, Subunit

Substances

  • Adjuvants, Immunologic
  • Antibodies
  • Antigen-Antibody Complex
  • Antigens, Neoplasm
  • CPG-oligonucleotide
  • CTAG1B protein, human
  • Cancer Vaccines
  • Immunoglobulin G
  • Membrane Proteins
  • Oligodeoxyribonucleotides
  • Vaccines, Subunit