Journal
INFLAMMATORY BOWEL DISEASES
Volume 21, Issue 8, Pages 1908-1917Publisher
OXFORD UNIV PRESS INC
DOI: 10.1097/MIB.0000000000000440
Keywords
vascular targeting; DSS-induced colitis; F8 antibody; muIL12p40
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Funding
- ETH Zurich
- Swiss National Science Foundation
- KTI MedTech Project
- EU FP7 PRIAT Project
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The antibody-based pharmacodelivery of cytokines to sites of disease has been extensively studied for various indications but not for the treatment of inflammatory bowel diseases. Here, we report that the alternatively spliced EDA domain of fibronectin, a marker of angiogenesis and of tissue remodeling, is expressed in the dextran sodium sulfate mouse model of colitis and in patients with inflammatory bowel conditions, while being virtually undetectable in most normal adult tissues. Radiolabeled preparations of the F8 antibody, specific to the EDA domain of fibronectin, were shown to selectively localize to sites of inflammation in mice with colitis, as revealed by autoradiographic analysis. Fusion proteins of the F8 antibody with various murine payloads (interleukin-4, the p40 subunit of interleukin-12, interleukin-13) were administered to mice with colitis. IL12p40-F8 mediated an anti-inflammatory activity, which was comparable with the one of cyclosporine, whereas F8-IL4 did not inhibit colitis and F8-IL13 worsened the inflammatory conditions.
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