title: The antibody-mediated targeted delivery of interleukin-10 inhibits endometriosis in a syngeneic mouse model.
abstract: BACKGROUND
  Endometriosis is still a highly underdiagnosed disease, and the current medical and surgical treatment of endometriosis is associated with a high recurrence rate. This study investigates the use of derivatives of the human antibody F8, specific to the alternatively spliced extra-domain A of fibronectin (Fn), for the imaging and treatment of endometriosis.
  
  
  METHODS
  Immunohistochemistry and immunofluorescence was used to evaluate antigen expression in endometriotic tissue of human endometriosis and of a syngeneic mouse model of the disease. The in vivo targeting performance of a fluorescent derivative of the F8 antibody was assessed by imaging mice with endometriosis using a near-infrared fluorescence imager, 24 h following i.v. injection of the antibody conjugate. Furthermore, the mouse model was used for therapy experiments using two recombinant F8-based immunocytokines [F8-interleukin-10 (IL10) and F8-IL2] or saline for the treatment groups.
  
  
  RESULTS
  A very strong vascular expression of splice isoforms of Fn and of tenascin-C was observed in human endometriotic lesions by immunohistochemistry and immunofluorescence techniques. After i.v. administration, a selective accumulation of the F8 antibody in endometriotic lesions could be observed in a syngeneic mouse model. These targeting data were used as a basis for therapy experiments with a pro-inflammatory (F8-IL2) and an anti-inflammatory (F8-IL10) cytokine fusion protein of the F8 antibody. The average lesion size in the F8-IL10 treatment group was clearly reduced compared with the saline control group and with the F8-IL2 group, for which no therapeutic effects were observed.
  
  
  CONCLUSIONS
  The F8 antibody targets endometriotic lesions in vivo in a mouse model of endometriosis and may be used for the non-invasive imaging of the disease and for the pharmacodelivery of anti-inflammatory cytokines, such as IL10.
authors.affiliation: Philochem AG, c/o ETH Zurich, Institute of Pharmaceutical Sciences, Wolfgang-Pauli-Str. 10 HCI E520, CH-8093 Zurich, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schwager
authors.forename: Frank
authors.initials: F
authors.lastname: Bootz
authors.forename: Patrick
authors.initials: P
authors.lastname: Imesch
authors.forename: Manuela
authors.initials: M
authors.lastname: Kaspar
authors.forename: Eveline
authors.initials: E
authors.lastname: Trachsel
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines / Q000097:blood; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D019265:Spectroscopy, Near-Infrared
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; C528643:F8 monoclonal antibody; D005353:Fibronectins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10