title: Adenoviruses with an αvβ integrin targeting moiety in the fiber shaft or the HI-loop increase tumor specificity without compromising antitumor efficacy in magnetic resonance imaging of colorectal cancer metastases.
abstract: BACKGROUND
  Colorectal cancer is often a deadly disease and cannot be cured at metastatic stage. Oncolytic adenoviruses have been considered as a new therapeutic option for treatment of refractory disseminated cancers, including colorectal cancer. The safety data has been excellent but tumor transduction and antitumor efficacy especially in systemic administration needs to be improved.
  
  
  METHODS
  Here, the utility of αvβ integrin targeting moiety Arg-Gly-Asp (RGD) in the Lys-Lys-Thr-Lys (KKTK) domain of the fiber shaft or in the HI-loop of adenovirus serotype 5 for increased tumor targeting and antitumor efficacy was evaluated. To this end, novel spleen-to-liver metastatic colorectal cancer mouse model was used and the antitumor efficacy was evaluated with magnetic resonance imaging (MRI).
  
  
  RESULTS
  Both modifications (RGD in the HI-loop or in the fiber shaft) increased gene transfer efficacy in colorectal cancer cell lines and improved tumor-to-normal ratio in systemic administration of the vector.
  
  
  CONCLUSIONS
  Antitumor potency was not compromised with RGD modified viruses suggesting increased safety profile and tumor specificity.
authors: Transplantation Laboratory, Haartman Institute and Finnish Institute of Molecular Medicine, University of Helsinki, Finland.
authors: Sergio
authors: S
authors: Lavilla-Alonso
authors: Gerd
authors: G
authors: Bauerschmitz
authors: Usama
authors: U
authors: Abo-Ramadan
authors: Juha
authors: J
authors: Halavaara
authors: Sophie
authors: S
authors: Escutenaire
authors: Iulia
authors: I
authors: Diaconu
authors: Turgut
authors: T
authors: Tatlisumak
authors: Anna
authors: A
authors: Kanerva
authors: Akseli
authors: A
authors: Hemminki
authors: Sari
authors: S
authors: Pesonen
mesh_terms: D000256:Adenoviridae / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D000818:Animals; D002213:Capsid / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000493:pharmacokinetics; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008279:Magnetic Resonance Imaging; D051379:Mice; D009362:Neoplasm Metastasis; D009842:Oligopeptides / Q000378:metabolism*; D009928:Organ Specificity; D019030:Receptors, Vitronectin / Q000378:metabolism*; D013160:Splenic Neoplasms / Q000556:secondary; D014018:Tissue Distribution; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
chemical_list: D009842:Oligopeptides; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; C047981:arginyl-glycyl-aspartic acid