title: Efficient gene therapy based targeting system for the treatment of inoperable tumors.
abstract: BACKGROUND
  A considerable percentage of tumors are not amenable to surgery. We have designed a simple and powerful targeting system that offers an alternative option for the multi-component pre-targeting strategies used clinically. This targeting system can be used for any type of solid tumors independent of the tumor type, thereby omitting the need to engineer unique antibodies for each specific application or tumour type. In the present study, we show the expression of a chimeric fusion protein, which contains the low-density lipoprotein receptor transmembrane domains and avidin, after local gene transfer and its ability to bind biotinylated compounds in vivo.
  
  
  METHODS
  Semliki Forest virus and lentivirus vectors were used to express the fusion protein with a high affinity binding site for biotinylated compounds in the tumor. Three different animal models and imaging modalities were used for the demonstration of the functionality and efficacy of the targeting system in vitro and in vivo.
  
  
  RESULTS
  We demonstrate targeting of biotinylated compounds after local gene transfer in vivo using two different gene transfer vectors. The findings were confirmed by immunohistochemistry, single-photon emission computed tomography and magnetic resonance imaging. The therapeutic efficacy was tested in a syngeneic rat glioma model by injecting biotinylated-(90) Yttrium into the tail vein of glioma bearing rats. The study demonstrates that animals, which were treated by using the gene therapy based targeting system, lived significantly longer than control animals.
  
  
  CONCLUSIONS
  Our gene therapy based targeting system is a promising tool for the treatment of inoperable tumors and other disease conditions, as well as diagnostic imaging.
authors.affiliation: AI Virtanen Institute, University of Eastern Finland, Kuopio, Finland. thomas.wirth@uef.fi
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
authors.forename: Jere Tuomas
authors.initials: JT
authors.lastname: Pikkarainen
authors.forename: Haritha Dhammika
authors.initials: HD
authors.lastname: Samaranayake
authors.forename: Pauliina
authors.initials: P
authors.lastname: Lehtolainen-Dalkilic
authors.forename: Hanna Pirita
authors.initials: HP
authors.lastname: Lesch
authors.forename: Kari Juhani
authors.initials: KJ
authors.lastname: Airenne
authors.forename: Varpu
authors.initials: V
authors.lastname: Marjomäki
authors.forename: Seppo Pasi Antero
authors.initials: SP
authors.lastname: Ylä-Herttuala
mesh_terms: D000818:Animals; D001360:Avidin / Q000235:genetics* / Q000378:metabolism; D019921:Biotinylation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012672:Semliki forest virus / Q000235:genetics
chemical_list: D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; D001360:Avidin