title: Biodistribution and antitumor effect of Cetuximab-targeted lentivirus.
abstract: Viral vectors are central tools for gene therapy. Targeting of the vector to desired tissues followed by expression of the therapeutic gene forms one of the most critical points in effective therapy. In this study we used streptavidin-displaying lentivirus conjugated to biotinylated anti-epidermal growth factor receptor (EGFR) antibody (Cetuximab) to target vector specifically to ovarian tumors. Biodistribution of the targeted virus was studied in nude mice with orthotropic SKOV-3m human ovarian carcinoma xenografts. Radiolabeled antibodies were conjugated to streptavidin-displaying lentiviruses and biodistribution of the virus after the intravenous delivery to tumor-bearing mice was monitored up to 6 days using combined SPECT/CT imaging modality. Organ samples were collected post mortem and specific organ activities were measured. The integration of lentivirus vectors in collected tissue samples was analyzed using qPCR and the expression of green fluorescent protein (GFP)-transgene was tested by enzyme-linked immunosorbent assay. Our results showed that lentiviruses conjugated to Cetuximab (Cet-LV) or control human IgG (IgG-LV) accumulated mainly to the liver and spleen of the mice and to lower extent to lung, kidneys and tumors. Strikingly, in 50% of the mice injected with cetuximab-targeted lentivirus no tumor tissue was found, whereas the remaining half showed a significant decrease in tumor size. We hypothesize/present data that lentivirus-mediated INF-αβ production together with tumor targeting could function as an effective antitumor treatment.
authors.affiliation: University of Eastern Finland, A.I. Virtanen institute, Department of Biotechnology and Molecular Medicine, P.O.B. 1627, 70211 Kuopio, Finland; Biocenter Kuopio, P.O.B. 1627, 70211 Kuopio, Finland.
authors.forename: Tuulia
authors.initials: T
authors.lastname: Huhtala
authors.forename: Minna U
authors.initials: MU
authors.lastname: Kaikkonen
authors.forename: Hanna P
authors.initials: HP
authors.lastname: Lesch
authors.forename: Sari
authors.initials: S
authors.lastname: Viitala
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Ale
authors.initials: A
authors.lastname: Närvänen
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001360:Avidin / Q000378:metabolism; D019921:Biotinylation; D045744:Cell Line, Tumor; D000068818:Cetuximab; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007205:Indium Radioisotopes; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D019809:Streptavidin / Q000235:genetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014161:Transduction, Genetic
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007205:Indium Radioisotopes; D001360:Avidin; D019809:Streptavidin; D000068818:Cetuximab
keywords: Cetuximab; Gene therapy; Lentivirus; Ovarian carcinoma; SPECT/CT; Targeting