%0 Journal Article
%A Compte, Marta
%A Alonso-Camino, Vanesa
%A Cuesta Martínez, Ángel
%A Santos-Valle, Patricia
%A Sánchez-Martín, David
%A López, Mariola
%A Vicario, José Luis 
%A Salas, Clara
%A Sanz, Laura
%A Álvarez-Vallina, Luis
%T Factory neovessels: engineered human blood vessels secreting therapeutic proteins as a new drug delivery system
%D 2010
%@ 0969-7128
%U https://hdl.handle.net/20.500.14352/93824
%X 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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