The Shiga toxin B-subunit targets antigen in vivo to dendritic cells and elicits anti-tumor immunity

Benoit Vingert, Olivier Adotevi, Delphine Patin, Steffen Jung, Protul Shrikant, Ludovic Freyburger, Cheryl Eppolito, Anita Sapoznikov, Mohamed Amessou, Françoise Quintin-Colonna, Wolf Herman Fridman, Ludger Johannes, Eric Tartour

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

The non-toxic B-subunit of Shiga toxin (STxB) interacts with the glycolipid Gb3, which is preferentially expressed on dendritic cells (DC) and B cells. After administration of STxB chemically coupled to OVA (STxB-OVA) in mice, we showed that the immunodominant OVA257-264 peptide restricted by kb molecules is specifically presented by CD11c+CD8α - DC, some of them displaying a mature phenotype. Using mice carrying a transgene encoding a diphtheria toxin receptor (DTR) under the control of the murine CD11c promoter, which allows inducible ablation of DC, we showed that DC are required for efficient priming of CTL after STxB-OVA vaccination. Immunization of mice with STxB-OVA induced OVA-specific CD8+ T cells detected ex vivo; these cells were long lasting, since they could be detected even 91 days after the last immunization and were composed of both central and memory T cells. Vaccination of mice with STxB-OVA and STxB coupled to E7, a protein derived from HPV16, inhibited tumor growth in prophylactic and therapeutic experiments. This effect was mainly mediated by CD8+ T cells. STxB therefore appears to be a powerful carrier directly targeting DC in vivo, resulting in a strong and durable CTL response associated with tumor protection.

Original languageEnglish (US)
Pages (from-to)1124-1135
Number of pages12
JournalEuropean Journal of Immunology
Volume36
Issue number5
DOIs
StatePublished - May 1 2006

Keywords

  • Cancer vaccine
  • Carrier
  • Cytotoxic T lympohocytes
  • Dendritic cell
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Vingert, B., Adotevi, O., Patin, D., Jung, S., Shrikant, P., Freyburger, L., Eppolito, C., Sapoznikov, A., Amessou, M., Quintin-Colonna, F., Fridman, W. H., Johannes, L., & Tartour, E. (2006). The Shiga toxin B-subunit targets antigen in vivo to dendritic cells and elicits anti-tumor immunity. European Journal of Immunology, 36(5), 1124-1135. https://doi.org/10.1002/eji.200535443