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


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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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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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).

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