Person:
Cuesta Martínez, Ángel

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First Name
Ángel
Last Name
Cuesta Martínez
URI
https://hdl.handle.net/20.500.14352/77488
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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Author: Sánchez-Martín, David × Has files: false ×

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    Factory neovessels: engineered human blood vessels secreting therapeutic proteins as a new drug delivery system
    (Gene Therapy, 2010) Compte, Marta; Alonso-Camino, Vanesa; Cuesta Martínez, Ángel; Santos-Valle, Patricia; Sánchez-Martín, David; López, Mariola; Vicario, José Luis ; Salas, Clara; Sanz, Laura; Álvarez-Vallina, Luis
    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.