title: A novel modular antigen delivery system for immuno targeting of human 6-sulfo LacNAc-positive blood dendritic cells (SlanDCs).
abstract: BACKGROUND
  Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767-777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.
  
  
  RESULTS
  Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.
  
  
  CONCLUSIONS
  In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines.
authors.affiliation: Institute of Immunology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Bippes
authors.forename: Anja
authors.initials: A
authors.lastname: Feldmann
authors.forename: Slava
authors.initials: S
authors.lastname: Stamova
authors.forename: Marc
authors.initials: M
authors.lastname: Cartellieri
authors.forename: Adrian
authors.initials: A
authors.lastname: Schwarzer
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wehner
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: E Peter
authors.initials: EP
authors.lastname: Rieber
authors.forename: Senming
authors.initials: S
authors.lastname: Zhao
authors.forename: Knut
authors.initials: K
authors.lastname: Schäkel
authors.forename: Achim
authors.initials: A
authors.lastname: Temme
authors.forename: R Hal
authors.initials: RH
authors.lastname: Scofield
authors.forename: Biji T
authors.initials: BT
authors.lastname: Kurien
authors.forename: Holger
authors.initials: H
authors.lastname: Bartsch
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
mesh_terms: D000606:Amino Sugars / Q000276:immunology*; D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000276:immunology*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008562:Membrane Glycoproteins; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology
chemical_list: C467438:6-sulfo-LacNac; D000606:Amino Sugars; D000941:Antigens; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D014612:Vaccines