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Targeting by affinity–matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform

Nature Biotechnology volume 15, pages 1271–1275 (1997)Cite this article

Abstract

The oncofetal fibronectin (B-FN) isoform is present in vessels of neoplastic tissues during angiogenesis but not in mature vessels. B-FN could therefore provide a target for diagnostic imaging and therapy of cancer. Phage display libraries have been used to isolate human antibody fragments with pan-species recognition of this isoform. We describe the use of these fragments in nude mice to target an aggressive tumor (grafted F9 murine teratocarcinoma). Imaging in real time was done by infrared photodetection of a chemically coupled fluorophore. The targeting was improved by use of affinity-matured fragments with low kinetic dissociation rates (koff=1.5×10−4 s−1) and also by engineering dimeric fragments via a C-terminal amphipathic helix.

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Author notes

  1. Ahuva Nissim & Paolo Neri

    Present address: Wolf son Centre for Structural Biology, Hebrew University of Jerusalem, Jerusalem, 91904, Israel

Authors and Affiliations

  1. Cambridge Centre for Protein Engineering—MRC Centre, Hills Rd., Cambridge, CB2 2QH, UK

    Dario Neri, Ahuva Nissim & Greg Winter

  2. Institut für Molekularbiologie und Biophysik, ETH Hönggerberg, CH-8093, Zürich, Switzerland

    Dario Neri, Lorenzo Tarli & Cornelia Halin

  3. Laboratorio di Biologia Cellulare, Istituto Nazionaleper la Ricerca sul Cancro, L.go Rosanna Benzi 10, 16132, Genova, Italy

    Barbara Carnemolla, Alessandra Leprini, Germano Querzè, Enrica Balza & Luciano Zardi

  4. Dipartimento di Biologia Molecolare, Universita' di Siena, Centro Didattico loc. Le Scotte, 53100, Siena, Italy

    Alessandro Pini

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Correspondence to Dario Neri.

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Neri, D., Carnemolla, B., Nissim, A. et al. Targeting by affinity–matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform. Nat Biotechnol 15, 1271–1275 (1997). https://doi.org/10.1038/nbt1197-1271

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