Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti–DC-SIGN antibody

• Published in: Blood Vol. 106; no. 4; pp. 1278 - 1285
• Main Authors: Tacken, Paul J., de Vries, I. Jolanda M., Gijzen, Karlijn, Joosten, Ben, Wu, Dayang, Rother, Russell P., Faas, Susan J., Punt, Cornelis J.A., Torensma, Ruurd, Adema, Gosse J., Figdor, Carl G.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.08.2005; The Americain Society of Hematology
• Subjects: Antibodies - therapeutic use; Antigen Presentation - immunology; Antigen-antibody reactions, antigen-antibody complexes, antibody-complement and others. Study of affinity. Antigen presentation; Antigens - immunology; Biological and medical sciences; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - pharmacokinetics; Dendritic Cells - immunology; Dendritic Cells - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hemocyanins - chemistry; Hemocyanins - pharmacokinetics; Humans; Immunity - drug effects; Immunotherapy - methods; Lectins, C-Type - chemistry; Lectins, C-Type - immunology; Molecular immunology; Protein Engineering; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - immunology; Recombinant Fusion Proteins - chemical synthesis; Recombinant Fusion Proteins - pharmacokinetics; T-Cell Antigen Receptor Specificity - immunology; T-Lymphocytes - immunology; Vaccines - chemical synthesis; Vaccines - pharmacokinetics; Human; Dendritic cell; Immunostimulation; Immune response; Vaccination; Naive cell; Activation; Memory lymphocyte; Antigen; T-Lymphocyte; Humanized antibody; Lectin DC-SIGN; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-01-0318

Current dendritic cell (DC)–based vaccines are based on ex vivo–generated autologous DCs loaded with antigen prior to readministration into patients. A more direct and less laborious strategy is to target antigens to DCs in vivo via specific surface receptors. Therefore, we developed a humanized antibody, hD1V1G2/G4 (hD1), directed against the C-type lectin DC-specific intercellular adhesion molecule 3–grabbing nonintegrin (DC-SIGN) to explore its capacity to serve as a target receptor for vaccination purposes. hD1 was cross-linked to a model antigen, keyhole limpet hemocyanin (KLH). We observed that the chimeric antibody-protein complex (hD1-KLH) bound specifically to DC-SIGN and was rapidly internalized and translocated to the lysosomal compartment. To determine the targeting efficiency of hD1-KLH, monocyte-derived DCs and peripheral blood lymphocytes (PBLs) were obtained from patients who had previously been vaccinated with KLH-pulsed DCs. Autologous DCs pulsed with hD1-KLH induced proliferation of patient PBLs at a 100-fold lower concentration than KLH-pulsed DCs. In addition, hD1-KLH–targeted DCs induced proliferation of naive T cells recognizing KLH epitopes in the context of major histocompatibility complex (MHC) classes I and II. We conclude that antibody-mediated targeting of antigen to DCs via DC-SIGN effectively induces antigen-specific naive as well as recall T-cell responses. This identifies DC-SIGN as a promising target molecule for DC-based vaccination strategies.