Experimental Therapeutics

British Journal of Cancer (2003) 88, 937–939. doi:10.1038/sj.bjc.6600751 www.bjcancer.com
Published online 18 March 2003

A33scFv–cytosine deaminase: a recombinant protein construct for antibody-directed enzyme-prodrug therapy

P M Deckert1, C Renner2, L S Cohen3, A Jungbluth1, G Ritter1, J R Bertino4, L J Old1 and S Welt1

  1. 1Medizinische Klinik III, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, D-12200 Berlin, Germany
  2. 2Medizinische Klinik I, Universitätskliniken des Saarlandes, D-66421 Homburg/Saar, Germany
  3. 3Ludwig Institute for Cancer Research – New York Branch, 1275 York Avenue, New York, NY 10021, USA
  4. 4Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

Correspondence: Dr PM Deckert, E-mail: deckert@medizin.fu-berlin.de

Received 29 April 2002; Revised 9 October 2002; Accepted 8 November 2002.

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Abstract

A recombinant fusion protein of colon carcinoma binding A33 single chain antibody with cytosine deaminase displayed specific antigen binding and enzyme activity in surface plasmon resonance and is catalytic activity assay. In vitro, it selectively increased the toxicity of 5-FC to A33 antigen-positive cells by 300-fold, demonstrating the potency of this ADEPT strategy.

Keywords:

tumour targeting, A33 antibody, antibody directed enzyme-producing therapy (ADEPT), colon carcinoma, recombinant fusion proteins