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. © 2010 Macmillan Publishers Limited All rights reserved.
CITATION STYLE
Compte, M., Alonso-Camino, V., Santos-Valle, P., Cuesta, Á. M., Sánchez-Martín, D., López, M. R., … Álvarez-Vallina, L. (2010). Factory neovessels: Engineered human blood vessels secreting therapeutic proteins as a new drug delivery system. Gene Therapy, 17(6), 745–751. https://doi.org/10.1038/gt.2010.33
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