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Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment

Nature Biotechnology volume 17, pages 984–988 (1999)Cite this article

Abstract

Molecules that selectively target and occlude new blood vessels would be useful for diagnosis and treatment of pathologies associated with angiogenesis. We show that a phage-derived human antibody fragment (L19) with high affinity for the ED-B domain of fibronectin, a marker of angiogenesis, selectively localizes to newly formed blood vessels in a rabbit model of ocular angiogenesis. The L19 antibody, chemically coupled to a photosensitizer and irradiated with red light, mediates complete and selective occlusion of ocular neovasculature and promotes apoptosis of the corresponding endothelial cells. These results demonstrate that new ocular blood vessels can be distinguished immunochemically from preexisting ones and suggest that the targeted delivery of photosensitizers may be effective in treating angiogenesis-related pathologies.

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Figure 1: Immunohistochemical studies of ocular structures using the L19 antibody.
Figure 2: Immunophotodetection of fluorescently labeled antibodies targeting ocular angiogenesis.
Figure 3: Macroscopic images of eyes of rabbits treated with photosensitizer conjugates.
Figure 4: Microscopic analysis of selective blood vessel occlusion.

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Acknowledgements

We thank Prof. Dr. M. Friedlander (La Jolla, CA) for advice in the implementation of the cornea micropocket assay, Dr. F. Bootz for technical assistance with rabbit anesthesia, S. Demartis for help with the synthesis of chlorin derivatives, and Dr. A. Brändli and Dr. V. Taylor for critically reading the manuscript. Financial support from the Swiss Federal Institute of Technology (D.N.), the Swiss Bundesamt für Bildung und Wissenschaft (within the frame of an EU BIOTEC-2 Project; D.N.), the Roche Research Foundation (M.B.), and the Stiftung für Wissenschaftliche Forschung (M.B.) is gratefully acknowledged.

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Authors and Affiliations

  1. Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Hönggerberg, Einsteinstrasse, Zürich, CH-8093, Switzerland

    Manfred Birchler, Francesca Viti & Dario Neri

  2. Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, Genova, 16132, Italy

    Luciano Zardi

  3. Department of Applied Life Sciences, Veterinär-Chirurgische Klinik der Universität Zürich, Eidgenössische Technische Hochschule Zürich, Winterthurerstrasse 190, Zürich, CH-8057, Switzerland

    Bernhard Spiess

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  1. Manfred Birchler
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  2. Francesca Viti
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  3. Luciano Zardi
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  5. Dario Neri
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Correspondence to Dario Neri.

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Birchler, M., Viti, F., Zardi, L. et al. Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment. Nat Biotechnol 17, 984–988 (1999). https://doi.org/10.1038/13679

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