A Human mAb Specific to Oncofetal Fibronectin Selectively Targets Chronic Skin Inflammation In Vivo Eveline Trachsel, Manuela Kaspar, Frank Bootz, Michael.

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A Human mAb Specific to Oncofetal Fibronectin Selectively Targets Chronic Skin Inflammation In Vivo Eveline Trachsel, Manuela Kaspar, Frank Bootz, Michael Detmar, Dario Neri Journal of Investigative Dermatology Volume 127, Issue 4, Pages 881-886 (April 2007) DOI: 10.1038/sj.jid.5700653 Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Immunohistochemistry with an L19 antibody fragment reveals EDB expression in human and murine psoriatic skin. (a) Expression of EDB-fibronectin is detected at the epidermal–dermal junction and around some vascular structures (b) but is not present in the healthy skin of the same patient. (c) A positive staining for EDB in the hyperplastic, delayed-type hypersensitivity-induced chronic-inflammatory lesions of the right ear in a VEGF-transgenic mouse, (d) whereas no staining was observed in the left, non-inflamed ear of the same animal. Bar=50μm. Journal of Investigative Dermatology 2007 127, 881-886DOI: (10.1038/sj.jid.5700653) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Biodistribution of 125I-labeled SIP(L19) in psoriatic mice shows selective accumulation of the antibody in the inflamed ear skin. (a) SIP(L19) was labeled with 125I was injected intravenously into psoriatic mice. Twenty-four hours after injection mice were killed and organs and ears were weighed and counted. The antibody preferentially accumulated in the inflamed ear, compared to normal organs. (b) An autoradiographic image of the ears 24hours after antibody injection (n=4). Journal of Investigative Dermatology 2007 127, 881-886DOI: (10.1038/sj.jid.5700653) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Ex vivo fluorescence microscopy analysis of ear sections from VEGF-transgenic mice reveals a selective accumulation of SIP(L19) compared with an irrelevant antibody. Mice were injected with Cy3-labeled SIP(L19) or SIP(HyHEL10), an antibody of irrelevant specificity in the mouse, 24hours before euthanasia. (a and b) Accumulation of SIP(L19)-Cy3 surrounding blood vessels in the chronically inflamed ear skin of VEGF-transgenic mice, whereas (c and d) no preferential antibody uptake was observed with SIP(HyHEL10)-Cy3. Bar=100μm. Journal of Investigative Dermatology 2007 127, 881-886DOI: (10.1038/sj.jid.5700653) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Photodynamic therapy with L19-SnChe6 does not lead to a therapeutic effect in psoriatic mice. Psoriatic mice were injected (3 × in 1 week intervals) with 160μm of L19-SnChe6 conjugate and irradiated 24hours after injection. Mice were photographed 1 day after the third irradiation. Increased swelling and reddening of inflamed ears (indicated by the arrows in (a) can be observed in mice treated with the L19-SnChe6, whereas (b) the ear swelling in psoriatic mice that had only been irradiated without previous injection of the antibody-photosensitizer conjugate had gone back to baseline. Journal of Investigative Dermatology 2007 127, 881-886DOI: (10.1038/sj.jid.5700653) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Effects of antibody-cytokine fusion proteins on chronic, psoriasis-like skin inflammation. Psoriatic mice were injected intravenously with different cytokine-fusion proteins. The plots show the (a) swelling of the right ear and of the (b) unsensitized left ear at different time points, as a result of the treatment with antibody-cytokine fusion proteins. Open squares: L19-IL2; open triangles, dashed line: L19-IL12; black circles, dashed line: L19-IL10; crosses: saline control. Journal of Investigative Dermatology 2007 127, 881-886DOI: (10.1038/sj.jid.5700653) Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions