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Factory neovessels: engineered human blood vessels secreting therapeutic proteins as a new drug delivery system

Gene Therapy volume 17, pages 745–751 (2010)Cite this article

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Abstract

Several works have shown the feasibility of engineering functional blood vessels in vivo using human endothelial cells (ECs). Going further, we explored the therapeutic potential of neovessels after gene-modifying the ECs for the secretion of a therapeutic protein. Given that these vessels are connected with the host vascular bed, we hypothesized that systemic release of the expressed protein is immediate. As a proof of principle, we used primary human ECs transduced with a lentiviral vector for the expression of a recombinant bispecific αCEA/αCD3 antibody. These ECs, along with mesenchymal stem cells as a source of mural cells, were embedded in Matrigel and subcutaneously implanted in nude mice. High antibody levels were detected in plasma for 1 month. Furthermore, the antibody exerted a therapeutic effect in mice bearing distant carcinoembryonic-antigen (CEA)-positive tumors after inoculation of human T cells. In summary, we show for the first time the therapeutic effect of a protein locally secreted by engineered human neovessels.

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Acknowledgements

This work was supported by grants from the Ministerio de Ciencia e Innovación (BIO2008-03233), the Comunidad Autónoma de Madrid (S-BIO-0236-2006) and the European Union (Immunonet–SUDOE) to LA-V; and from the Fondo de Investigación Sanitaria (PI061621) to LS. MC was supported by Instituto de Salud Carlos III (Contrato Rio Hortega, CM06/00055). DS-M was supported by a Comunidad Autónoma de Madrid/European Social Fund training grant (FPI-000531). LS is an investigator from the Ramón y Cajal Program (Ministerio de Ciencia e Innovación), co-financed by the European Social Fund. VAC is a predoctoral fellow from the Gobierno Vasco (BFI07.132).

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Authors and Affiliations

  1. Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, Madrid, Spain

    M Compte, V Alonso-Camino, P Santos-Valle, Á M Cuesta, D Sánchez-Martín, M R López, L Sanz & L Álvarez-Vallina

  2. Histocompatibility Department, Centro de Transfusión, Madrid, Spain

    J L Vicario

  3. Pathology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain

    C Salas

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  1. M Compte
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  2. V Alonso-Camino
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  3. P Santos-Valle
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  4. Á M Cuesta
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  5. D Sánchez-Martín
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  6. M R López
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  7. J L Vicario
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  8. C Salas
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  9. L Sanz
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  10. L Álvarez-Vallina
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Corresponding authors

Correspondence to L Sanz or L Álvarez-Vallina.

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Compte, M., Alonso-Camino, V., Santos-Valle, P. et al. Factory neovessels: engineered human blood vessels secreting therapeutic proteins as a new drug delivery system. Gene Ther 17, 745–751 (2010). https://doi.org/10.1038/gt.2010.33

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