title: CD47 Enhances In Vivo Functionality of Artificial Antigen-Presenting Cells.
abstract: OBJECTIVE
  Artificial antigen-presenting cells, aAPC, have successfully been used to stimulate antigen-specific T-cell responses in vitro as well as in vivo. Although aAPC compare favorably with autologous dendritic cells in vitro, their effect in vivo might be diminished through rapid clearance by macrophages. Therefore, to prevent uptake and minimize clearance of aAPC by macrophages, thereby increasing in vivo functionality, we investigated the efficiency of "don't eat me" three-signal aAPC compared with classical two-signal aAPC.
  
  
  METHODS
  To generate "don't eat me" aAPC, CD47 was additionally immobilized onto classical aAPC (aAPC(CD47+)). aAPC and aAPC(CD47+) were analyzed in in vitro human primary T-cell and macrophage cocultures. In vivo efficiency was compared in a NOD/SCID T-cell proliferation and a B16-SIY melanoma model.
  
  
  RESULTS
  This study demonstrates that aAPC(CD47+) in coculture with human macrophages show a CD47 concentration-dependent inhibition of phagocytosis, whereas their ability to generate and expand antigen-specific T cells was not affected. Furthermore, aAPC(CD47+)-generated T cells displayed equivalent killing abilities and polyfunctionality when compared with aAPC-generated T cells. In addition, in vivo studies demonstrated an enhanced stimulatory capacity and tumor inhibition of aAPC(CD47+) over normal aAPC in conjunction with diverging biodistribution in different organs.
  
  
  CONCLUSIONS
  Our data for the first time show that aAPC functionalized with CD47 maintain their stimulatory capacity in vitro and demonstrate enhanced in vivo efficiency. Thus, these next-generation aAPC(CD47+) have a unique potential to enhance the application of the aAPC technology for future immunotherapy approaches.
authors.affiliation: Department of Internal Medicine 5-Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Bruns
authors.affiliation: Institute of Cell Engineering, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bessell
authors.affiliation: Division of Hematology, Department of Medicine, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Varela
authors.affiliation: Institute of Cell Engineering, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Carl
authors.initials: C
authors.lastname: Haupt
authors.affiliation: Institute of Cell Engineering, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Jerry
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Internal Medicine 5-Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors.forename: Shirin
authors.initials: S
authors.lastname: Pasemann
authors.affiliation: Department of Internal Medicine 5-Hematology/Oncology, University of Erlangen, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mackensen
authors.affiliation: Institute of Cell Engineering, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Mathias
authors.initials: M
authors.lastname: Oelke
authors.affiliation: Institute of Cell Engineering, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Schneck
authors.affiliation: Institute of Cell Engineering, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland. cschuet4@jhmi.edu chri.sch@hotmail.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Schütz
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D051928:CD47 Antigen / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D064593:Heterografts; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D051928:CD47 Antigen; C497894:CD47 protein, human