Selective targeting of adenovirus to αvβ3 integrins, VEGFR2 and Tie2 endothelial receptors by angio-adenobodies
| Autor: | Anna Rita Bellu, Hidde J. Haisma, Anu Kariath, T. M. Geel, Arend Bouma, Marianne G. Rots, Gera Kamps |
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| Přispěvatelé: | Damage and Repair in Cancer Development and Cancer Treatment (DARE), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Biopharmaceuticals, Discovery, Design and Delivery (BDDD) |
| Rok vydání: | 2010 |
| Předmět: |
Alpha-v beta-3
Angiogenesis Genetic enhancement Integrin Pharmaceutical Science Antineoplastic Agents GENE-TRANSFER Adenoviridae Cell Line TUMOR ANGIOGENESIS BISPECIFIC ANTIBODIES Viral vector Mice DELIVERY chemistry.chemical_compound Drug Delivery Systems SINGLE-CHAIN DIABODY Cell Line Tumor Animals Humans Adenovirus Amino Acid Sequence Receptor IN-VIVO Mice Inbred BALB C Reporter gene THERAPEUTIC TARGET biology Endothelial Cells Integrin alphaVbeta3 Receptor TIE-2 Vascular Endothelial Growth Factor Receptor-2 CANCER Molecular biology Up-Regulation VEGFR2 Tie2 chemistry CELLS Cancer cell Cancer research biology.protein VECTORS Peptides Single-Chain Antibodies alpha(v)beta(3) Integrins |
| Zdroj: | International Journal of Pharmaceutics, 391(1-2), 155-161. Elsevier Bedrijfsinformatie b.v. |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2010.02.032 |
| Popis: | Tumor angiogenesis is a prominent mechanism, driving the development and progression of solid tumors and the formation of cancer cell metastasis. Newly formed tumor vessels represent an elective target for the activity and the delivery of cancer therapeutics. We targeted adenovirus (Ad5) to endothelial receptors which are up-regulated during the formation of new blood vessels, to enhance the efficiency of anticancer gene therapy applications.Bifunctional angio-adenobodies were constructed by the fusion of a single chain antibody directed against the adenoviral fiber knob, to different peptides recognizing the alpha(v)beta(3) integrins, VEGFR2 and Tie2 receptors on endothelial cells. The angio-adenobodies were coupled to the adenoviral vector, containing luciferase and GFP as reporter genes.In vitro data showed selective targeting of the Ad5 to the endothelial receptors both in mouse (H5V) and human cell lines (HUVEC). H5V cells, refractory to Ad5 infection, showed high level of luciferase expression when cells were infected with targeted virus. Viral transgene expression increased in HUVEC cells when cells were infected with Ad5 conjugated with angio-adenobody thereby demonstrating the affinity of the peptides for human endothelial cells also. In vivo data obtained from mice bearing a C26 colon carcinoma subcutaneously show viral transgene expression only in tumors infected with angio-adenobodies retargeted adenovirus.The results of the present study demonstrate that endothelial targeted angio-adenobodies represent a versatile tool to direct adenovirus from its native receptors to the integrins a alpha(v)beta(3), VEGFR2 and Tie2 receptors that are fundamental in many angiogenesis related diseases such as cancer. (C) 2010 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
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