Therapeutic administration of a synthetic CpG oligodeoxynucleotide triggers formation of anti-CpG antibodies Journal Article
| Authors: | Karbach, J.; Neumann, A.; Wahle, C.; Brand, K.; Gnjatic, S.; Jager, E. |
| Article Title: | Therapeutic administration of a synthetic CpG oligodeoxynucleotide triggers formation of anti-CpG antibodies |
| 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 CpGODNs. ©2012 AACR. |
| Keywords: | clinical article; controlled study; treatment response; unclassified drug; monotherapy; adjuvant therapy; neoplasms; nausea; membrane proteins; drug potency; drug hypersensitivity; dyspnea; pruritus; thorax pain; immune response; antigens, neoplasm; immunoglobulin g; cancer vaccines; ny eso 1 antigen; nucleotide sequence; cpg oligodeoxynucleotide; cancer immunization; agatolimod; recombinant protein; erythema; antibody specificity; immunological adjuvant; skin disease; immunostimulation; hot flush; antibodies; cross reaction; adjuvants, immunologic; injection site erythema; immunoglobulin g antibody; tachycardia; vaccines, subunit; antibody production; urticaria; antibody titer; oligodeoxyribonucleotides; cancer antibody; bacterial vaccine; antigen-antibody complex; cpg oligodeoxynucleotide antibody; phosphorothioic acid; allergic rash |
| Journal Title: | Cancer Research |
| Volume: | 72 |
| Issue: | 17 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2012-09-01 |
| Start Page: | 4304 |
| End Page: | 4310 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-12-0257 |
| PROVIDER: | scopus |
| PUBMED: | 22738916 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 October 2012" - "CODEN: CNREA" - "Source: Scopus" |
