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: Kathrin Schwager, Frank Bootz, Patrick Imesch, Manuela Kaspar, Eveline Trachsel, Dario Neri
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 26 Issue 9 Pg. 2344-52 (Sep 2011) ISSN: 1460-2350 [Electronic] England
• PMID: 21705369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Cytokines
• F8 monoclonal antibody
• Fibronectins
• Interleukin-2
• Recombinant Fusion Proteins
• Interleukin-10

Topics

• Alternative Splicing
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Cytokines (blood)
• Endometriosis (drug therapy, pathology)
• Female
• Fibronectins (genetics, immunology)
• Humans
• Interleukin-10 (therapeutic use)
• Interleukin-2 (therapeutic use)
• Mice
• Mice, Inbred C57BL
• Recombinant Fusion Proteins (immunology, therapeutic use)
• Spectroscopy, Near-Infrared