TY - JOUR
T1 - The Shiga toxin B-subunit targets antigen in vivo to dendritic cells and elicits anti-tumor immunity
AU - Vingert, Benoit
AU - Adotevi, Olivier
AU - Patin, Delphine
AU - Jung, Steffen
AU - Shrikant, Protul
AU - Freyburger, Ludovic
AU - Eppolito, Cheryl
AU - Sapoznikov, Anita
AU - Amessou, Mohamed
AU - Quintin-Colonna, Françoise
AU - Fridman, Wolf Herman
AU - Johannes, Ludger
AU - Tartour, Eric
N1 - Funding Information:
1 Radio Astronomy at the Haystack Observatory of the Northeast Radio Observatory Corporation (NEROC) is supported by a grant from the National Science Foundation.
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
KW - Cancer vaccine
KW - Carrier
KW - Cytotoxic T lympohocytes
KW - Dendritic cell
KW - Tumor immunity
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U2 - 10.1002/eji.200535443
DO - 10.1002/eji.200535443
M3 - Article
C2 - 16568496
AN - SCOPUS:33646569995
SN - 0014-2980
VL - 36
SP - 1124
EP - 1135
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 5
ER -