RT Journal Article
T1 Enhanced antiangiogenic therapy with antibody‐collagen XVIII NC1 domain fusion proteins engineered to exploit matrix remodeling events
A1 Sánchez‐Arévalo Lobo, Víctor J.
A1 Cuesta Martínez, Ángel
A1 Sanz, Laura
A1 Compte, Marta
A1 García, Pascal
A1 Prieto, Jesús
A1 Blanco, Francisco J.
A1 Álvarez‐Vallina, Luis
AB Antiangiogenic therapy is nowadays one of the most active fields in cancer research. The first strategies, aimed at inhibiting tumor vascularization, included upregulation of endogenous inhibitors and blocking of the signals delivered by angiogenic factors. But interaction between endothelial cells and their surrounding extracellular matrix also plays a critical role in the modulation of the angiogenic process. This study introduces a new concept to enhance the efficacy of antibody‐based antiangiogenic cancer therapy strategies, taking advantage of a key molecular event occurring in the tumor context: the proteolysis of collagen XVIII, which releases the endogenous angiogenesis inhibitor endostatin. By fusing the collagen XVIII NC1 domain to an antiangiogenic single‐chain antibody, a multispecific agent was generated, which was efficiently processed by tumor‐associated proteinases to produce monomeric endostatin and fully functional trimeric antibody fragments. It was demonstrated that the combined production in the tumor area of complementary antiangiogenic agents from a single molecular entity secreted by gene‐modified cells resulted in enhanced antitumor effects. These results indicate that tailoring recombinant antibodies with extracellular matrix‐derived scaffolds is an effective approach to convert tumor progression associated processes into molecular clues for improving antibody‐based therapies.
PB Wiley
SN 0020-7136
SN 1097-0215
YR 2006
FD 2006
LK https://hdl.handle.net/20.500.14352/92808
UL https://hdl.handle.net/20.500.14352/92808
LA eng
NO Sánchez-Arévalo Lobo VJ, Cuesta AM, Sanz L, et al. Enhanced antiangiogenic therapy with antibody-collagen XVIII NC1 domain fusion proteins engineered to exploit matrix remodeling events. Int J Cancer. 2006;119(2):455-462. doi:10.1002/ijc.21851
NO Ministerio de Ciencia y Tecnología (España)
DS Docta Complutense
RD 20 ago 2024