Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-59120
Schwager, K; Bootz, F; Imesch, P; Kaspar, M; Trachsel, E; Neri, D (2011). The antibody-mediated targeted delivery of interleukin-10 inhibits endometriosis in a syngeneic mouse model. Human Reproduction, 26(9):2344-2352.
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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 noninvasive imaging of the disease and for the pharmacodelivery of anti-inflammatory cytokines, such as IL10.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||17 Feb 2012 13:01|
|Last Modified:||03 Dec 2013 21:46|
|Publisher:||Oxford University Press|
|ISSN:||0268-1161 (P) 1460-2350 (E)|
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