2026-09-16T07:42:23Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1588692025-04-30T19:33:32Zcom_10366_3992com_10366_3947com_10366_3946com_10366_3823col_10366_3993

Puerto-Camacho, Pilar Amaral, Ana Teresa Lamhamedi-Cherradi, Salah-Eddine Menegaz, Brian A. Castillo-Ecija, Helena Ordóñez García, José Luis Domínguez, Saioa Jordan-Perez, Carmen Diaz-Martin, Juan Romero-Pérez, Laura Lopez-Alvarez, Maria Civantos-Jubera, Gema Robles-Frías, María José Biscuola, Michele Ferrer, Cristina Mora, Jaume Cuglievan, Branko Schadler, Keri Seifert, Oliver Kontermann, Roland Pfizenmaier, Klaus Simón, Laureano Fabre, Myriam Carcaboso, Ángel M. Ludwig, Joseph A. de Álava, Enrique 2024-07-09T10:39:24Z 2024-07-09T10:39:24Z 2019 Puerto-Camacho, P., Amaral, A. T., Lamhamedi-Cherradi, S. E., Menegaz, B. A., Castillo-Ecija, H., Ordóñez, J. L., ... & de Álava, E. (2019). Preclinical efficacy of endoglin-targeting antibody–drug conjugates for the treatment of Ewing sarcoma. Clinical Cancer Research, 25(7), 2228-2240. 1078-0432 http://hdl.handle.net/10366/158869 10.1158/1078-0432.CCR-18-0936 [EN] Endoglin (ENG; CD105) is a coreceptor of the TGFb family that is highly expressed in proliferating endothelial cells. Often coopted by cancer cells, ENG can lead to neo-angiogenesis and vasculogenic mimicry in aggressive malignancies. It exists both as a transmembrane cell surface protein, where it primarily interacts with TGFb, and as a soluble matricellular protein (sENG) when cleaved by matrix metal-loproteinase 14 (MMP14). High ENG expression has been associated with poor prognosis in Ewing sarcoma, an aggressive bone cancer that primarily occurs in adolescents and young adults. However, the therapeutic value of ENG targeting has not been fully explored in this disease. Experimental Design: We characterized the expression pattern of transmembrane ENG, sENG, and MMP14 in preclinical and clinical samples. Subsequently, the antineoplastic potential of two novel ENG-targeting monoclonal antibody–drug conjugates (ADC), OMTX503 and OMTX703, which differed only by their drug payload (nigrin-b A chain and cytolysin, respectively), was assessed in cell lines and preclinical animal models of Ewing sarcoma. Results: Both ADCs suppressed cell proliferation in proportion to the endogenous levels of ENG observed in vitro. Moreover, the ADCs significantly delayed tumor growth in Ewing sarcoma cell line–derived xenografts and patient-derived xenografts in a dose-dependent manner. Conclusions: Taken together, these studies demonstrate potent preclinical activity of first-in-class anti-ENG ADCs as a nascent strategy to eradicate Ewing sarcoma. eng http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional Endoglin Ewing Sarcoma Preclinical Efficacy of Endoglin-Targeting Antibody–Drug Conjugates for the Treatment of Ewing Sarcoma info:eu-repo/semantics/article