Dendritic cell KLH loading requirements for efficient CD4+ T-cell priming and help to peptide-specific cytotoxic T-cell response, in view of potential use in cancer vaccines.
This study focuses on a Keyhole Limpet Hemocyanin (KLH) adjuvant strategy to augment efficacy of dendritic cell-based vaccines that use class I-restricted peptides. Requirements for loading dendritic cells (DC) with KLH were first determined in order to optimally prime CD4(+) T cells. These KLH-loaded cells were pulsed with antigenic peptide and cultured with T cells to induce a cytotoxic T lymphocyte (CTL) response against the peptide. Such a concomitant presentation of KLH and peptide by the same DC strongly augmented the peptide-specific CTL response, as compared to the response induced by DC pulsed with the peptide alone. This adjuvant effect was more pronounced for poorly immunogenic antigens. The use of optimised peptide and KLH-loaded DC may improve the efficacy of therapeutic anti-tumour peptide vaccination.
Millard
A L
AL
Unité de Thérapie Cellulaire, Institut Jean-Godinot, 1 Avenue du Général Koenig, 51056 Cedex, Reims, France.
Ittelet
D
D
Schooneman
F
F
Bernard
J
J
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000276:immunology*; D006433:Hemocyanins / Q000008:administration & dosage*; D015395:Histocompatibility Antigens Class I / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D015848:Interleukin-5; D022223:Vaccines, Subunit; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin