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Volume 2
     

A Fusion Gene for the Treatment of Cancer (Scavidin)

   
Project

QLK3-2001-02166

Cell factory area

3.1.3

EU Contribution

1,072,000 Euro

Duration

36 months

Type

RS

Starting date

01 January 2002

Keywords
avidin-biotin binding
biotinylation
gene therapy
malignant glioma
ABSTRACT

Cancer is an important cause of morbidity and mortality in the European Union. In the most severe solitary cancers, such as malignant glioma, very little, if any, improvement has been made in the prognosis of patients during the last twenty years in spite of improved surgical techniques, radiation and chemotherapy. In many solitary tumours that cannot be removed by surgery or at margins of the tumour cavity after resection, it would be of great advantage if strong treatment effect could be targeted to the treatment area without severe systemic side effects. For that purpose we have cloned a new fusion gene "Scavidin" which contains intracellular and membrane-spanning domains of Scavenger receptor ligated to avidin. Scavidin will be transfected to target tissue with local gene therapy. Targeted treatment is achieved by binding of biotinylated therapeutic compounds to Scavidin that will be only expressed in the transfected tissue. Scavidin will form a two-component target-specific therapeutic system that should reduce systemic side-effects of the therapeutic compounds while leading to high concentration and efficient accumulation of biotinylated drugs in the treatment area.

OBJECTIVES

The main objectives are:

  • development of Scavidin and second-generation improved Scavidin molecules with optimal avidin-biotin binding properties and a possibility to regulate and/or target the expression to specific tissues.
  • development of biotinylated ligands for Scavidin targeted therapy system.
  • testing safety and efficacy of Scavidin delivery system in human malignant glioma in vivo.
  • testing safety and efficacy of Scavidin delivery system in human malignant glioma in vivo.
DESCRIPTION OF THE WORK

Scavidin and biotinylated compounds that contain one or several therapeutic substances will form a new two-component target-specific therapeutic system. Firstly, target tissue is transfected with adenovirus or pseudotyped retrovirus containing Scavidin and secondly, biotinylated therapeutic compounds, isotopes or liposomes are given systemically 3-10 days after the transfection. As already shown in our preliminary experiments, the first generation Scavidin can lead to binding of biotinylated compounds to target tissues. Scavidin technology should allow the use of very low concentrations of biotinylated compounds which should reduce systemic side effects of the therapeutic compounds while leading to high concentration and efficient accumulation of the biotinylated compounds in the treatment area.

DELIVERABLES

Scavidin and second-generation Scavidin gene transfer vectors, Scavidin vectors with regulated and/or tissue-specific promoters, biotinylated therapeutic compounds for use in in vivo studies, toxicology and efficacy of Scavidin targeted therapeutic gene delivery system in rat malignant glioma model in vivo; and safety and efficacy of Scavidin gene delivery system in human malignant glioma in vivo.

CONSORTIUM
COORDINATOR
 
Prof. Seppo Ylš-Herttuala
A.I.Virtanen Institute
University of Kuopio
70211 Kuopio, Finland
Tel: +358-17-162 075
Fax: +358-17-163 751
Seppo.Ylaherttuala@uku.fi
 
PARTNERS
 
Dr Georg Breier
Max Planck Institute for Physiological
and Clinical Research
Parkstr. 1
61231 Bad Nauheim, Germany
Tel: +49-6032-705 293
Fax: +49-6032-722 59
g.breier@kerckhoff.mpg.de

Prof. Giovanni Paganelli
Division of Nuclear Medicine
European Institute of Oncology
Via Ripamonti 435
20141 Milan, Italy
Tel: +39-02-5748 9043
Fax: +39-02-5748 9040
direzione.mnu@ieo.it

Prof. John F. Martin
Department of Medicine
University College London
5, University Street
London WC1E 6JJ, United Kingdom
Tel: +44-20-7679-6352
Fax: +44-20-7679-6379
John.Martin@ucl.ac.uk

Dr David Sellwood
Ark Therapeutics Ltd
6 Warren Mews
London W1T 6AR, United Kingdom
Tel: +44-20-7388-7722
Fax: +44-20-7388-7805
dsellwood@arktherapeutics.com