Compte, MartaAlonso-Camino, VanesaCuesta Martínez, ÁngelSantos-Valle, PatriciaSánchez-Martín, DavidLópez, MariolaVicario, José LuisSalas, ClaraSanz, LauraÁlvarez-Vallina, Luis2024-01-182024-01-182010Compte 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. 2010;17(6):745-751. doi:10.1038/gt.2010.330969-712810.1038/gt.2010.33https://hdl.handle.net/20.500.14352/93824Several 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.engjournal article1476-5462https://doi.org/10.1038/gt.2010.33https://www.nature.com/articles/gt201033metadata only accessCiencias Biomédicas24 Ciencias de la Vida