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

Dario Neri, Barbara Carnemolla, Ahuva Nissim, Alessandra Leprini, Germano Querzè, Enrica Balza, Alessandro Pini, Lorenzo Tarli, Cornelia Halin, Paolo Neri, Luciano Zardi, Greg Winter

Research output: Contribution to journalArticle

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 (k(off)= 1.5 x 10-4 s-1) and also by engineering dimeric fragments via a C-terminal amphipathic helix.

Original languageEnglish
Pages (from-to)1271-1275
Number of pages5
JournalNature Biotechnology
Volume15
Issue number12
Publication statusPublished - Nov 1997

Keywords

  • Antibody engineering
  • Oncofetal protein
  • Single-chain antibody

ASJC Scopus subject areas

  • Microbiology

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    Neri, D., Carnemolla, B., Nissim, A., Leprini, A., Querzè, G., Balza, E., Pini, A., Tarli, L., Halin, C., Neri, P., Zardi, L., & Winter, G. (1997). Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform. Nature Biotechnology, 15(12), 1271-1275.