CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans.
Clin Cancer Res
; 14(17): 5626-34, 2008 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-18765557
ABSTRACT
PURPOSE:
CpG oligodeoxynucleotides (CpG-ODN) are being investigated as cancer vaccine adjuvants because they mature plasmacytoid dendritic cells (PDC) into potent antigen-presenting cells. CpG-ODN also induce PDC to secrete chemokines that alter lymphocyte migration. Whether CpG-ODN TLR signals enhance antigen-specific immunity and/or trafficking in humans is unknown. EXPERIMENTALDESIGN:
We conducted a phase I study of CpG-ODN (1018 ISS) given as a vaccine adjuvant with granulocyte-macrophage colony-stimulating factor (GM-CSF) to induce T-cell immunity to a peptide vaccine from the tumor-associated antigen hTERT.RESULTS:
The adjuvant effect was limited; only 1 of 16 patients showed a high-frequency hTERT-specific tetramer CD8(+) T-cell response. However, CpG-ODN induced marked, transient peripheral blood lymphopenia. Biopsies showed dense lymphocytic infiltration at the vaccine site clustered around activated PDC. In vitro, CpG-ODN-treated PDC induced T-cell migration, showing that CpG-ODN stimulation of human PDC was sufficient to chemoattract T cells.CONCLUSIONS:
Our results show that (a) CpG-ODN with GM-CSF may not be an effective adjuvant strategy for hTERT peptide vaccines but (b) GM-CSF/CpG-ODN causes a PDC-mediated chemokine response that recruits T-cell migration to the peripheral tissues. These findings suggest a novel therapeutic role for targeted injections of CpG-ODN to direct lymphocyte migration to specific sites such as the tumor bed.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Oligodesoxirribonucleotídeos
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Células Dendríticas
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Linfócitos T
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Fator Estimulador de Colônias de Granulócitos e Macrófagos
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Telomerase
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Vacinas Anticâncer
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Vacinas de Subunidades Antigênicas
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article