87 results on '"Navarro-Zapata A"'
Search Results
2. Newer generations of multi-target CAR and STAb-T immunotherapeutics: NEXT CART Consortium as a cooperative effort to overcome current limitations
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Beatriz Martín-Antonio, Belén Blanco, África González-Murillo, Laura Hidalgo, Jordi Minguillón, Gema Pérez-Chacón, Next Generation CART MAD Consortium, Lucía Fernández, Halin Bareke, Andrés París-Muñoz, Adriana Mañas, Cristina Aguirre-Portolés, Alfonso Navarro-Zapata, Carmen Mestre-Durán, Marta Ibáñez-Navarro, Laura Clares-Villa, Sara Naharro, Antonio Perez-Martinez, Marcos Aldea, María Gaibar, Javier Ruiz-Navarro, Manuel Izquierdo, Juan M. Zapata, África González Murillo, Elena García Sánchez, Jorge García Martínez, Alba Rubio San Simón, Blanca Herrero, Gonzalo García Aguilera, Beatriz Horcajo Morera, Manuel Ramírez Orellana, Belén Blanco-Durango, Anais Jiménez-Reinoso, Rodrigo Lázaro-Gorines, Ivana Zagorac, Antonio Tapia Galisteo, Ángel Ramirez-Fernández, Laura Díez-Alonso, Carmen Dominguez-Alonso, Ainhoa Erce-Llamazares, Oana Hangiu, Laura Rubio Pérez, Marina Gómez Rosel, Alejandro Segura Tudela, Javier Arroyo-Ródena, Luis Álvarez-Vallina, Miguel Ángel Rodríguez Milla, Patricia García Rodríguez, Beatriz Somovilla Crespo, Javier García-Castro, Esperanza Esquinas Tarifa, Juana Serrano-López, Pilar Llamas-Sillero, and Beatriz Martin-Antonio
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CAR-T cells ,NK cells ,TILs ,TCR therapy ,immunological synapse ,cancer ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Adoptive T cellular immunotherapies have emerged as relevant approaches for treating cancer patients who have relapsed or become refractory (R/R) to traditional cancer treatments. Chimeric antigen receptor (CAR) T-cell therapy has improved survival in various hematological malignancies. However, significant limitations still impede the widespread adoption of these therapies in most cancers. To advance in this field, six research groups have created the “NEXT Generation CART MAD Consortium” (NEXT CART) in Madrid’s Community, which aims to develop novel cell-based immunotherapies for R/R and poor prognosis cancers. At NEXT CART, various basic and translational research groups and hospitals in Madrid concur to share and synergize their basic expertise in immunotherapy, gene therapy, and immunological synapse, and clinical expertise in pediatric and adult oncology. NEXT CART goal is to develop new cell engineering approaches and treatments for R/R adult and pediatric neoplasms to evaluate in multicenter clinical trials. Here, we discuss the current limitations of T cell-based therapies and introduce our perspective on future developments. Advancement opportunities include developing allogeneic products, optimizing CAR signaling domains, combining cellular immunotherapies, multi-targeting strategies, and improving tumor-infiltrating lymphocytes (TILs)/T cell receptor (TCR) therapy. Furthermore, basic studies aim to identify novel tumor targets, tumor molecules in the tumor microenvironment that impact CAR efficacy, and strategies to enhance the efficiency of the immunological synapse between immune and tumor cells. Our perspective of current cellular immunotherapy underscores the potential of these treatments while acknowledging the existing hurdles that demand innovative solutions to develop their potential for cancer treatment fully.
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- 2024
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3. Inherited human ezrin deficiency impairs adaptive immunity
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García-Solís, Blanca, Van Den Rym, Ana, Martinez-Martínez, Laura, Franco, Teresa, Pérez-Caraballo, Jareb J., Markle, Janet, Cubillos-Zapata, Carolina, Marín, Ana V., Recio, María J., Regueiro, José R., Navarro-Zapata, Alfonso, Mestre-Durán, Carmen, Ferreras, Cristina, Martín Cotázar, Carla, Mena, Roció, de la Calle-Fabregat, Carlos, López-Lera, Alberto, Fernández Arquero, Miguel, Pérez-Martínez, Antonio, López-Collazo, Eduardo, Sánchez-Ramón, Silvia, Casanova, Jean-Laurent, Martínez-Barricarte, Rubén, de la Calle-Martín, Oscar, and Pérez de Diego, Rebeca
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- 2023
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4. NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells
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Marta Ibáñez-Navarro, Adrián Fernández, Adela Escudero, Gloria Esteso, Carmen Campos-Silva, Miguel Ángel Navarro-Aguadero, Alejandra Leivas, Beatriz Ruz Caracuel, Carlos Rodríguez-Antolín, Alejandra Ortiz, Alfonso Navarro-Zapata, Carmen Mestre-Durán, Manuel Izquierdo, María Balaguer-Pérez, Cristina Ferreras, Joaquín Martínez-López, Mar Valés-Gómez, Antonio Pérez-Martínez, and Lucía Fernández
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pediatric acute leukemia ,T cell lymphoblastic leukemia ,NKG2D ,NKG2D CAR T cells ,leukemia initiating cells ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionRefractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation.MethodsIn this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells’ cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality.ResultsIn vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells.DiscussionThe data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.
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- 2023
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5. Formin-like 1 β phosphorylation at S1086 is necessary for secretory polarized traffic of exosomes at the immune synapse in Jurkat T lymphocytes
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Fernández-Hermira, Sara, primary, Sanz-Fernández, Irene, additional, Barbeito, Pablo, additional, Navarro-Zapata, Alfonso, additional, Pérez-Martínez, Antonio, additional, Garcia-Gonzalo, Francesc R., additional, Calvo, Víctor, additional, and Izquierdo, Manuel, additional
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- 2024
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6. Ruxolitinib does not completely abrogate the functional capabilities of TLR4/9 ligand-activated NK cells
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Carmen Mestre-Durán, Carla Martín-Cortázar, Blanca García-Solís, Alicia Pernas, Lidia Pertíñez, Víctor Galán, Luisa Sisinni, Laura Clares-Villa, Alfonso Navarro-Zapata, Karima Al-Akioui, Adela Escudero, Cristina Ferreras, and Antonio Pérez-Martínez
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NK cells ,TLR4 ligand ,TLR9 ligand ,ruxolitinib ,JAK - STAT signaling pathway ,TLR pathway ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionNatural killer (NK) cells are lymphocytes from the innate immune system part of the first defense barrier against infected and transformed cells, representing 5%-15% of peripheral blood lymphocytes. The cytotoxic capacity of NK cells is controlled by a balance between inhibitory and activating NK receptors expressed on their surface, which recognize and interact with the ligands on stressed cells. The cytokines involved in NK cell activation, proliferation, survival, and cytotoxicity are signaled mainly through the Janus kinase and signal transducer and activator of transcription proteins (JAK/STAT) pathway. NK cells are also activated in response to pathogens through Toll-like receptors (TLRs) expressed on their surface. Ruxolitinib is a specific JAK1/2 inhibitor approved for treating myelofibrosis and for steroid-refractory acute and chronic graft-versus-host disease (SR-GvHD).MethodsPurified NK cells from healthy donors were stimulated with two TOLL-like receptor ligands, LPS and CpG, in the presence of different concentrations of Ruxolitinib.ResultsThis study showed the effects of ruxolitinib on TLR4 and TLR9 ligand-activated NK cells from healthy donors. Ruxolitinib did not completely inhibit STAT3 phosphorylation and had a moderate effect on NK cell cytokine activation via the TLR pathway. Only the highest doses of ruxolitinib led to a decrease in the pro-inflammatory cytokines tumor necrosis factor α, interferon-γ, interleukin-6, and interleukin-1β. The cytotoxic capacity of stimulated NK cells versus K562, SEM, and MV-4-11 cell lines was reduced by increasing doses of ruxolitinib, but it was not completely abolished and we observed no major changes in degranulation capacity. Phenotypic changes were observed in activated NK cells in the presence of ruxolitinib. In a small cohort of pediatric patients treated with ruxolitinib for SR-GvHD, we observed no decrease in NK cell counts; however, further prospective studies with larger cohorts are necessary to confirm this finding.DiscussionIn summary, our results showed that the functional capabilities and phenotype of NK cells activated through TLR4/9 agonists were not completely abolished by the inhibition of the JAK-STAT pathway by ruxolitinib.
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- 2023
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7. P1428: IMPLICATIONS OF THE RUXOLITINIB (JAK1/JAK2 INHIBITOR) ON GRAFT-VERSUS-LEUKAEMIA EFFECT MEDIATED BY THE NK CELL.
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C. Durán, C. Martín Cortázar, C. Ferreras, A. Navarro Zapata, L. Clares Villa, K. Al-akioui, A. Escuredo, A. Pernas, V. Galán, D. Bueno, L. Sisinni, and A. Pérez Martínez
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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8. NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells
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Ibáñez-Navarro, Marta, primary, Fernández, Adrián, additional, Escudero, Adela, additional, Esteso, Gloria, additional, Campos-Silva, Carmen, additional, Navarro-Aguadero, Miguel Ángel, additional, Leivas, Alejandra, additional, Caracuel, Beatriz Ruz, additional, Rodríguez-Antolín, Carlos, additional, Ortiz, Alejandra, additional, Navarro-Zapata, Alfonso, additional, Mestre-Durán, Carmen, additional, Izquierdo, Manuel, additional, Balaguer-Pérez, María, additional, Ferreras, Cristina, additional, Martínez-López, Joaquín, additional, Valés-Gómez, Mar, additional, Pérez-Martínez, Antonio, additional, and Fernández, Lucía, additional
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- 2023
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9. Donor selection for adoptive cell therapy with CD45RA− memory T cells for patients with coronavirus disease 2019, and dexamethasone and interleukin-15 effects on the phenotype, proliferation and interferon gamma release
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Karima Al-Akioui-Sanz, Bárbara Pascual-Miguel, Mariana Díaz-Almirón, Carmen Mestre-Durán, Alfonso Navarro-Zapata, Laura Clares-Villa, Carla Martín-Cortázar, José Luis Vicario, Miguel Ángel Moreno, Antonio Balas, Raquel De Paz, Jordi Minguillón, Antonio Pérez-Martínez, and Cristina Ferreras
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Cancer Research ,Transplantation ,Oncology ,Immunology ,Immunology and Allergy ,Cell Biology ,Genetics (clinical) - Published
- 2023
10. SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy
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C. Ferreras, B. Pascual-Miguel, C. Mestre-Durán, A. Navarro-Zapata, L. Clares-Villa, C. Martín-Cortázar, R. De Paz, A. Marcos, J. L. Vicario, A. Balas, F. García-Sánchez, C. Eguizabal, C. Solano, M. Mora-Rillo, B. Soria, and A. Pérez-Martínez
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memory T cells (Tmem) ,adoptive cell therapy (ACT) ,COVID-19 ,lymphopenia ,biobank ,Biology (General) ,QH301-705.5 - Abstract
Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus’ complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA– memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA– memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA– subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available “off-the-shelf” to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.
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- 2021
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11. Technological intensity in manufacturing trade between ASEAN and the EU: challenges and opportunities
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José De Hevia, Amadeo Navarro Zapata, and María Arrazola
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General Social Sciences ,General Business, Management and Accounting - Abstract
This article analyses trade flows EU-ASEAN, focusing on export performance and technological intensity, covering the years 2004–2016. The aim of this paper is to analyse to what extent, a further trade integration between the EU and ASEAN, could generate business opportunities for countries in both trading blocs. This analysis could serve as a basis for designing and implementing effective policies and strategies by policymakers in the face of a deepening EU-ASEAN trade integration. Therefore, a detailed analysis of the degree of complementarity of trade patterns, the weight of intra-industry trade, and the revealed comparative advantages allows us to outline some of those challenges and opportunities. Results suggest that intra-industry trade is moderate, mainly focused on few manufactures, accounting for a low value of total trade flows between the two blocs, and concentrated in a few countries. The Lafay index analysis suggests that the EU and ASEAN are natural partners regarding the technological patterns of the revealed comparative advantages; therefore, a deepening in trade integration between this trading blocs could allow to exploit those comparative advantages.
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- 2023
12. Drivers of technological export performance in Spain: A regional approach, 2000-2016.
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Navarro Zapata, Amadeo, Vacas, María Arrazola, and de Hevia Payá, José
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ECONOMIC development ,EXPORTS ,INTERNATIONAL trade ,INDUSTRIAL policy - Abstract
Having a high export capacity is a core element of achieving sustained long-term economic growth. To attain this goal, the technological sophistication of exports plays a key role (Hausmann et al. 2007, Rodrik 2006, Minondo 2010). In the context of stimulating exports with a high level of sophistication, it is crucial to identify the main drivers of exports in general and of high-tech exports. Specifically, the aim of this article is to study the determinants of the international trade flows of manufacturers according to their technological content in the case of Spanish regions. The results obtained show strong evidence of the relevance of considering the technological content of manufacturers when studying the drivers of trade flows at the regional level. Moreover, the findings have significant implications for trade and industrial policies in Spain, a country that traditionally exhibits large trade imbalances, since these outcomes could enhance the effectiveness of policies targeting the technological upgrading of Spanish exports. [ABSTRACT FROM AUTHOR]
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- 2023
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13. A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia
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Álvaro Martínez-Rubio, Salvador Chulián, Cristina Blázquez Goñi, Manuel Ramírez Orellana, Antonio Pérez Martínez, Alfonso Navarro-Zapata, Cristina Ferreras, Victor M. Pérez-García, and María Rosa
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CAR T ,mathematical model ,acute lymphoblastic leukemia ,B cell ,bone marrow ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients’ experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.
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- 2021
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14. Determinants of High-tech Exports: New Evidence from OECD Countries
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Navarro Zapata, Amadeo, primary, Arrazola, María, additional, and de Hevia, José, additional
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- 2023
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15. NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and n vivo but fail to eliminate leukemiai nitiating cells
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Instituto de Salud Carlos III, Fundación CRIS contra el Cáncer, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Ibáñez-Navarro, Marta, Fernández, Adrián, Escudero, Adela, Esteso, Gloria, Campos-Silva, Carmen, Navarro-Aguadero, Miguel Ángel, Leivas, Alejandra, Ruz Caracuel, Beatriz, Rodriguez-Antolín, Carlos, Ortiz, Alejandra, Navarro-Zapata, Alfonso, Mestre-Durán, Carmen, Izquierdo, Manuel, Instituto de Salud Carlos III, Fundación CRIS contra el Cáncer, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Ibáñez-Navarro, Marta, Fernández, Adrián, Escudero, Adela, Esteso, Gloria, Campos-Silva, Carmen, Navarro-Aguadero, Miguel Ángel, Leivas, Alejandra, Ruz Caracuel, Beatriz, Rodriguez-Antolín, Carlos, Ortiz, Alejandra, Navarro-Zapata, Alfonso, Mestre-Durán, Carmen, and Izquierdo, Manuel
- Abstract
[Introduction]: Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation. [Methods]: In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells’ cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality. [Results]: In vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells. [Discussion]: The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.
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- 2023
16. DataSheet_1_NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells.pdf [Dataset]
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Ibáñez-Navarro, Marta, Fernández, Adrián, Escudero, Adela, Esteso, Gloria, Campos-Silva, Carmen, Navarro-Aguadero, Miguel Ángel, Leivas, Alejandra, Ruz Caracuel, Beatriz, Rodriguez-Antolín, Carlos, Ortiz, Alejandra, Navarro-Zapata, Alfonso, Mestre-Durán, Carmen, Izquierdo, Manuel, Balaguer-Pérez, María, Ferreras, Cristina, Martínez-López, Joaquín, Valés-Gómez, Mar, Pérez-Martínez, Antonio, Fernández, Lucía, Ibáñez-Navarro, Marta, Fernández, Adrián, Escudero, Adela, Esteso, Gloria, Campos-Silva, Carmen, Navarro-Aguadero, Miguel Ángel, Leivas, Alejandra, Ruz Caracuel, Beatriz, Rodriguez-Antolín, Carlos, Ortiz, Alejandra, Navarro-Zapata, Alfonso, Mestre-Durán, Carmen, Izquierdo, Manuel, Balaguer-Pérez, María, Ferreras, Cristina, Martínez-López, Joaquín, Valés-Gómez, Mar, Pérez-Martínez, Antonio, and Fernández, Lucía
- Abstract
[Introduction]: Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation., [Methods]: In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells’ cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality., [Results]: In vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells., [Discussion]: The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.
- Published
- 2023
17. Determinants of High-tech Exports: New Evidence from OECD Countries
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José De Hevia, Amadeo Navarro Zapata, and María Arrazola
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Economics and Econometrics - Abstract
High export capacity is a key element for sustained long-term economic growth. To achieve this goal, the technological sophistication of exports plays a key role. To enhance exports with a high level of technological sophistication, it is critical to target key drivers of high-tech exports. Hence, this article studies the determinants of international trade flows of manufactures according to their technological content in the case of OECD countries. Given a panel of 35 countries and 15 years (2004 to 2018), panel data estimation techniques are used in the analysis. In addition, two alternative measures have been considered to measure the importance of high-technology content manufacturing exports: High-tech manufacturing exports and high-tech manufacturing exports as a share of total employment. Results obtained show strong evidence of the relevance of variables such as gross fixed capital formation on total employment, the land area per capita, the percentage of university graduates relative to the population group, R&D expenditure in terms of GDP, the stock of inward foreign direct investment in terms of GDP, imports of high-tech manufactures as a share of GDP, the quality of national governance and regulation, the country population and EU membership as determinants of technology-intensive exports. Moreover, the findings have significant implications for trade and industrial policies in OECD countries, to ensure the effectiveness of policies targeting the technological upgrading of exports.
- Published
- 2023
18. Ruxolitinib does not completely abrogate the functional capabilities of TLR4/9 ligand-activated NK cells
- Author
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Mestre-Durán, Carmen, primary, Martín-Cortázar, Carla, additional, García-Solís, Blanca, additional, Pernas, Alicia, additional, Pertíñez, Lidia, additional, Galán, Víctor, additional, Sisinni, Luisa, additional, Clares-Villa, Laura, additional, Navarro-Zapata, Alfonso, additional, Al-Akioui, Karima, additional, Escudero, Adela, additional, Ferreras, Cristina, additional, and Pérez-Martínez, Antonio, additional
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- 2023
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19. Donor selection for adoptive cell therapy with CD45RA− memory T cells for patients with coronavirus disease 2019, and dexamethasone and interleukin-15 effects on the phenotype, proliferation and interferon gamma release
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Al-Akioui-Sanz, Karima, primary, Pascual-Miguel, Bárbara, additional, Díaz-Almirón, Mariana, additional, Mestre-Durán, Carmen, additional, Navarro-Zapata, Alfonso, additional, Clares-Villa, Laura, additional, Martín-Cortázar, Carla, additional, Vicario, José Luis, additional, Moreno, Miguel Ángel, additional, Balas, Antonio, additional, De Paz, Raquel, additional, Minguillón, Jordi, additional, Pérez-Martínez, Antonio, additional, and Ferreras, Cristina, additional
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- 2022
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20. Donor selection for adoptive cell therapy with CD45RA
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Karima, Al-Akioui-Sanz, Bárbara, Pascual-Miguel, Mariana, Díaz-Almirón, Carmen, Mestre-Durán, Alfonso, Navarro-Zapata, Laura, Clares-Villa, Carla, Martín-Cortázar, José Luis, Vicario, Miguel Ángel, Moreno, Antonio, Balas, Raquel, De Paz, Jordi, Minguillón, Antonio, Pérez-Martínez, and Cristina, Ferreras
- Abstract
We have previously demonstrated the safety and feasibility of adoptive cell therapy with CD45RAWe performed a longitudinal analysis from previously severe acute respiratory syndrome coronavirus 2-infected and infection-naïve individuals covering 21 months from infection and 10 months after full vaccination with the BNT162b2 Pfizer/BioNTech vaccine.We observed that cellular responses are maintained over time. Humoral responses increased after vaccination but were gradually lost. In addition, dexamethasone did not alter cell functionality or proliferation of CD45RAOur results suggest that the best donors for adoptive cell therapy would be recovered individuals and 2 months after vaccination, although further studies with larger cohorts would be needed to confirm this finding. Dexamethasone did not affect the characteristics of the memory T cells at a concentration used in the clinical practice and IL-15 showed a positive effect on SARS-CoV-2-specific CD45RA
- Published
- 2022
21. P1428: IMPLICATIONS OF THE RUXOLITINIB (JAK1/JAK2 INHIBITOR) ON GRAFT-VERSUS-LEUKAEMIA EFFECT MEDIATED BY THE NK CELL.
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Durán, C., primary, Martín Cortázar, C., additional, Ferreras, C., additional, Navarro Zapata, A., additional, Clares Villa, L., additional, Al-akioui, K., additional, Escuredo, A., additional, Pernas, A., additional, Galán, V., additional, Bueno, D., additional, Sisinni, L., additional, and Pérez Martínez, A., additional
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- 2022
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22. Donor’s graft ex vivo T‐cell depletion with fludarabine reduces graft‐versus‐host disease signs and improves survival after intestinal transplantation – an experimental study
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Rodrigo Papa-Gobbi, Carmen Mestre, Pablo Gonzalez-Navarro, Nidia M. Arreola, Pablo Stringa, Mariana Alejandra Machuca, Francisco Hernández-Oliveros, Bárbara Pascual-Miguel, Alfonso Navarro-Zapata, María Elena Vela, Antonio Pérez-Martínez, Sara C Pires-Lobo, and Ane M. Andres
- Subjects
medicine.medical_specialty ,T-Lymphocytes ,medicine.medical_treatment ,Graft vs Host Disease ,030230 surgery ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Animals ,Transplantation, Homologous ,Medicine ,Transplantation ,Intestine transplantation ,business.industry ,Immunosuppression ,medicine.disease ,Rash ,Rats ,Fludarabine ,Diarrhea ,surgical procedures, operative ,Graft-versus-host disease ,Rats, Inbred Lew ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Vidarabine ,Ex vivo ,medicine.drug - Abstract
Intestinal passenger T leukocytes are responsible for graft-versus-host disease (GvHD) in intestinal transplantation (ITx). We hypothesized that ex vivo fludarabine treatment of the bowel graft would diminish the risk of GvHD and improve overall survival post-transplant. We performed isolated heterotopic small bowel transplantations from Lewis (LEW) to Brown Norway (BN) rat strains, which generated GvHD signs from the fourth day post-transplant. These symptoms included rash, weight loss, piloerection, and diarrhea. The grafts of one of the experimental groups were immersed and sealed in cold Celsior preservation solution with 1000 µm fludarabine for 1 h, prior to its implantation into recipient animals. No histological signs of intestinal tissue alterations were observed after fludarabine treatment. Fludarabine-treated bowel recipients showed significantly later and milder clinical signs of GvHD and reduced total donor cell chimerism, as determined by flow cytometry using strain-specific anti-HLA antibodies. Additionally, fludarabine treatment prolonged recipients' overall survival (13.5 days ± 0.3 days vs. 9.2 days ± 0.5). We conclude that active modification of the intestinal leukocyte composition is advantageous in our ITx animal model. Immunosuppression with fludarabine during the surgical procedure, which could be translated directly to the clinic, protects bowel recipients from GvHD and improves overall post-transplant survival.
- Published
- 2020
23. Immunotherapy: MEMORY-LIKE NK CELLS: A PROMISING THERAPY FOR EWING SARCOMA
- Author
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C. Martín Cortázar, A. Navarro Zapata, C. Mestre Durán, L. Clares Villa, K. Al-Akioui, C. Ferreras, and A. Perez-Martinez
- Subjects
Cancer Research ,Transplantation ,Oncology ,Immunology ,Immunology and Allergy ,Cell Biology ,Genetics (clinical) - Published
- 2022
24. Evolución de la intensidad tecnológica y ventajas comparativas de las exportaciones de manufacturas españolas durante el periodo 2000-2018
- Author
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Amadeo Navarro Zapata
- Abstract
Este estudio analiza la evolución de la intensidad tecnológica de las exportaciones españolas de manufacturas durante el periodo 2000-2018, concluyendo que los resultados no han sido muy satisfactorios en relación con la mejora del componente tecnológico de las exportaciones españolas. Asimismo, se analizan las ventajas comparativas de las principales manufacturas con mayor intensidad tecnológica, con el fin de que sirva de ayuda en la elección de sectores estratégicos dentro de la nueva estrategia PASE.
- Published
- 2021
25. A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia
- Author
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Cristina Blázquez Goñi, Cristina Ferreras, Álvaro Martínez-Rubio, Salvador Chulián, Manuel Ramírez Orellana, Alfonso Navarro-Zapata, María Rosa, Víctor M. Pérez-García, Antonio Pérez Martínez, Matemáticas, [Martínez-Rubio,Á, Chulián,S, Rosa,M] Department of Mathematics, Universidad de Cádiz, Puerto Real, Cádiz, Spain. [Martínez-Rubio,Á, Blázquez Goñi,C, Rosa,M] Biomedical Research and Innovation Institute of Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Cádiz, Spain. [Blázquez Goñi,C] Department of Pediatric Hematology and Oncology, Hospital de Jerez, Cádiz, Spain. [Ramírez Orellana,M] Department of Paediatric Haematology and Oncology, Instituto Investigación Sanitaria La Princesa, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. [Pérez Martínez,A, Navarro-Zapata,A, Ferreras,C] Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. [Pérez Martínez,A] Pediatric Hemato-Oncology Department, Hospital Universitario La Paz, Madrid, Spain. [Pérez-García,VM] Mathematical Oncology Laboratory (MOLAB), Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha, Ciudad Real, Spain. [Pérez-García,VM] Departamento de Matemáticas, Escuela Técnica Superior de Ingenieros Industriales, Universidad de Castilla-La Mancha, Ciudad Real, Spain., and This work was partially supported by the Fundación Española para la Ciencia y la Tecnología (UCA PR214), the Asociación Pablo Ugarte (APU, Spain), Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000154), Ministry of Science and Technology, Spain (PID2019-110895RB-I00), and Inversión Territorial Integrada de la Provincia de Cádiz (ITI-0038-2019).
- Subjects
0301 basic medicine ,CAR T ,Leucemia-linfoma linfoblástico de células precursoras ,Disease ,Immunotherapy, Adoptive ,Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets::B-Lymphocyte Subsets [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical [Medical Subject Headings] ,0302 clinical medicine ,Subgrupos de linfocitos B ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological [Medical Subject Headings] ,Biology (General) ,Young adult ,Child ,Spectroscopy ,B-Lymphocytes ,B cell ,Dynamics (mechanics) ,Médula ósea ,Diseases::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma::Precursor B-Cell Lymphoblastic Leukemia-Lymphoma [Medical Subject Headings] ,General Medicine ,Computer Science Applications ,Chemistry ,Leukemia ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Niño ,Modelos teóricos ,Car t cells ,bone marrow ,QH301-705.5 ,acute lymphoblastic leukemia ,Models, Biological ,Catalysis ,Receptores quiméricos de antígenos ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,medicine ,Humans ,Persons::Persons::Age Groups::Child [Medical Subject Headings] ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,business.industry ,Organic Chemistry ,Anatomy::Hemic and Immune Systems::Immune System::Bone Marrow [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive [Medical Subject Headings] ,medicine.disease ,Chimeric antigen receptor ,030104 developmental biology ,Phenomena and Processes::Immune System Phenomena::Immunity::Adaptive Immunity::Immunologic Memory [Medical Subject Headings] ,Cancer research ,Bone marrow ,business ,Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::B-Lymphocytes [Medical Subject Headings] ,Immunologic Memory ,mathematical model - Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model., This work was partially supported by the Fundacion Espanola para la Ciencia y la Tecnologia (UCA PR214), the Asociacion Pablo Ugarte (APU, Spain), Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000154), Ministry of Science and Technology, Spain (PID2019110895RB-I00), and Inversion Territorial Integrada de la Provincia de Cadiz (ITI-0038-2019).
- Published
- 2021
26. A Mathematical Description of the Bone Marrow Dynamics of CAR T-Cell Therapy in B-cell Childhood Acute Lymphoblastic Leukemia
- Author
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Cristina Blázquez Goñi, Salvador Chulián, Alfonso Navarro-Zapata, Víctor M. Pérez-García, Antonio Pérez Martínez, Manuel Ramírez Orellana, Cristina Ferreras, María Rosa, and Álvaro Martínez-Rubio
- Subjects
applied_mathematics ,medicine.anatomical_structure ,B-Cell Childhood Acute Lymphoblastic Leukemia ,business.industry ,medicine ,Cancer research ,CAR T-cell therapy ,Bone marrow ,Car t cells ,business ,B cell - Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells and CAR T cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T cells and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load and tumor burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.
- Published
- 2021
27. Evolución de la intensidad tecnológica y ventajas comparativas de las exportaciones de manufacturas españolas durante el periodo 2000-2018
- Author
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Navarro Zapata, Amadeo, primary
- Published
- 2021
- Full Text
- View/download PDF
28. Breaking Barriers in B-Acute Lymphoblastic Leukemia Treatment: Experience of a Tertiary Hospital with the Use of a Tandem Dual CAR-T 19/22 in Pediatric & AYA Patients
- Author
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González-Martínez, Berta, Galán-Gómez, Víctor, Minguillon Pedreno, Jordi, Navarro-Zapata, Alfonso, Mirones-Aguilar, Isabel, Sánchez-Zapardiel, Elena, Echecopar, Carlos, Martínez-Romera, Isabel, and Pérez-Martínez, Antonio
- Published
- 2023
- Full Text
- View/download PDF
29. Optimizing the procedure to manufacture clinical‐grade NK cells for adoptive immunotherapy
- Author
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Lucía Fernández, Alfonso Navarro-Zapata, Cristina Ferreras, Diego Lanzarot, Alicia Pernas, Carlos Rodriguez-Antolin, Alejandra Leivas, Marta Cobo, Aurora Viejo, Joaquín Martínez, Gema Casado, Beatriz Ruz-Caracuel, Carmen Mestre, María Vela, Adela Escudero, Isabel Mirones, Nerea Matamala, Adrián Fernández, Antonio Pérez-Martínez, and UAM. Departamento de Pediatría
- Subjects
0301 basic medicine ,Cancer Research ,Medicina ,medicine.medical_treatment ,T cell ,Cell ,NK cell activation and expansion ,Peripheral blood mononuclear cell ,lcsh:RC254-282 ,Article ,Oncología ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Cancer immunotherapy ,Clinical‐grade manufacturing ,medicine ,Hematología ,clinical-grade manufacturing ,Cytotoxicity ,Chemistry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,CliniMACS Prodigy ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Stem cell ,NKAE cells ,NK cell immunotherapy - Abstract
Natural killer (NK) cells represent promising tools for cancer immunotherapy. We report the optimization of an NK cell activation–expansion process and its validation on clinical‐scale. Methods: RPMI‐1640, stem cell growth medium (SCGM), NK MACS and TexMACS were used as culture mediums. Activated and expanded NK cells (NKAE) were obtained by coculturing total peripheral blood mononuclear cells (PBMC) or CD45RA+ cells with irradiated K562mbIL15‐41BBL or K562mbIL21‐41BBL. Fold increase, NK cell purity, activation status, cytotoxicity and transcriptome profile were analyzed. Clinical‐grade NKAE cells were manufactured in CliniMACS Prodigy. Results: NK MACS and TexMACs achieved the highest NK cell purity and lowest T cell contamination. Obtaining NKAE cells from CD45RA+ cells was feasible although PBMC yielded higher total cell numbers and NK cell purity than CD45RA+ cells. The highest fold expansion and NK purity were achieved by using PBMC and K562mbIL21‐41BBL cells. However, no differences in activation and cytotoxicity were found when using either NK cell source or activating cell line. Transcriptome profile showed to be different between basal NK cells and NKAE cells expanded with K562mbIL21‐41BBL or K562mbIL15‐41BBL. Clinical‐grade manufactured NKAE cells complied with the specifications from the Spanish Regulatory Agency. Conclusions: GMP‐grade NK cells for clinical use can be obtained by using different starting cells and aAPC, This work was supported by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI18/01301 to Pérez‐Martínez A, CRIS Foundation to Beat Cancer to Escudero A, Fernández A; Navarro A, Mirones I, and Fundación Mari Paz Jiménez Casado and La Sonrisa de Álex to Vela M.
- Published
- 2021
30. A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia
- Author
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Martínez-Rubio, Álvaro, primary, Chulián, Salvador, additional, Blázquez Goñi, Cristina, additional, Ramírez Orellana, Manuel, additional, Pérez Martínez, Antonio, additional, Navarro-Zapata, Alfonso, additional, Ferreras, Cristina, additional, Pérez-García, Victor M., additional, and Rosa, María, additional
- Published
- 2021
- Full Text
- View/download PDF
31. A Mathematical Description of the Bone Marrow Dynamics of CAR T-Cell Therapy in B-cell Childhood Acute Lymphoblastic Leukemia
- Author
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Martínez-Rubio, Álvaro, primary, Chulián, Salvador, additional, Blázquez Goñi, Cristina, additional, Pérez Martínez, Antonio, additional, Ramírez Orellana, Manuel, additional, Navarro-Zapata, Alfonso, additional, Ferreras, Cristina, additional, Pérez-García, Victor Manuel, additional, and Rosa, María, additional
- Published
- 2021
- Full Text
- View/download PDF
32. Expression of infiltrating bone marrow natural killer cell receptors in pediatric acute leukemia
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Mestre Durán, Carmen, Hidalgo, Sandra, Ferreras, Cristina, Uranga, Cecilia, Clares, Laura, Navarro Zapata, Alfonso, Calvo, Carlota, Aguilar, Yurena, Guerra-García, Pilar, Escudero, Adela, Pernas, Alicia, Gálvez Buerba, Eva Mª, Galán, Víctor, González, Berta, Ramírez-Labrada, Ariel, Pardo, Julián, and Pérez-Martínez, Antonio
- Subjects
Leukemia ,Bone marrow ,NK cells - Abstract
of the poster presented at SIOP 2021, the 53th Annual Congress of the International Society of Pediatric Oncology, Virtual, 21-24 october 2021.-- E-Poster Topic: Disease Orientated / AS01 Haematology / AS01.a Acute Lymphoblastic Leukaemia.-- PV0061 / #709.
- Published
- 2021
33. Estudio fenotípico de células NK infiltradas en médula ósea (BiNK) en pacientes pediátricos con leucemia aguda
- Author
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Mestre Durán, Carmen, Hidalgo, Sandra, Ferreras, Cristina, Uranga, Cecilia, Navarro Zapata, Alfonso, Calvo, Carlota, Clares, Laura, Martín-Cortázar, Carla, Aguilar, Yurena, Al-akioui, Karima, Escudero, Adela, Pernas, Alicia, Galán, Víctor, Guerra-García, Pilar, Gálvez Buerba, Eva Mª, González, Berta, Ramírez-Labrada, Ariel, Pardo, Julián, and Pérez-Martínez, Antonio
- Subjects
Médula ósea ,NK células ,Cancer - Abstract
3 figuras.-- Comunicación oral presentada en el LXIII Congreso Nacional de la SEHH (Sociedad Española de Hematología y Hemoterapia) y XXXVII Congreso Nacional de la SETH (Sociedad Española de Trombosis y Hemostasia), Pamplona, 14-16 Octubre 2021. [Introducción] La leucemia es el cáncer más común en la población pediátrica. Aproximadamente el 20% de los pacientes con leucemia linfoide aguda (LLA) y el 40% con leucemia mieloide aguda (LMA) recaen de la enfermedad. Es de vital importancia en el contexto de la recaída el estudio de la pérdida de la inmunovigilancia y el papel que presentan las células NK en este contexto. Para tratar de disminuir las tasas de recaída de la enfermedad. El objetivo de este estudio es evaluar el fenotipo y papel de las células NK infiltradas en médula ósea (BiNK) en pacientes con LLA y LMA. [Métodos] Se recogieron células mononucleares de médula ósea (BMMCs) procedentes de pacientes pediátricos con LLA-B (n=16) y LMA (n=4) en el Hospital Universitario La Paz. Se monitorizaron y analizaron las BiNK en el diagnóstico, seguimiento y recaída de la enfermedad. Se analizó su fenotipo mediante citometría de flujo, comprobando la expresión en superficie de los siguientes receptores activadores e inhibidores: CD56, CD3, CD16, NKG2D, NKp44, NKp46, CD69, CD57, TIM-3, LAG- 3, PD-1. Se examinaron también 3 ligandos de las células BiNK presentes en las células blásticas de los pacientes: PD-1, LAG-3 y TIM-3. Se estudió además la capacidad funcional de las células BiNK a través del ensayo de degranulación CD107a, por citometría de flujo. [Resultados] Los pacientes con LLA mostraron niveles similares de células BiNK en las diferentes fases del estudio, mientras que los pacientes con LMA presentaron una menor infiltración de las células BiNK durante el seguimiento y recaída de la enfermedad (Figura 1). Al diagnóstico se observa una alta expresión de los receptores activadores NKp46, NKG2D y CD57, mientras que los receptores inhibidores muestran una baja expresión en LLA y LMA. Los ligandos de los receptores inhibidores de células BiNK se encuentran altamente expresados en las células blásticas en pacientes con LLA y LMA (Figura 2). Durante el seguimiento de la enfermedad, la subpoblación CD56+ CD16- en las células BiNK de pacientes con LMA presentan una reducción de los receptores activadores. En el contexto de la recaída, las células BiNK muestran una expresión disminuida de NKG2D en pacientes con LLA y LMA. Los receptores inhibidores mantienen una expresión baja a excepción la LMA en recaída, donde se observa un aumento de la expresión de TIM-3 en las células BiNK. Esto se corresponde con una elevada expresión de su ligando, Galectina-9, en las células blásticas. No obstante, los ligandos analizados disminuyen respecto al diagnóstico en los pacientes con LLA, a excepción de Galectina-9. La capacidad degranulativa de las células BiNK se mantiene en los pacientes con LLA y LMA en recaída respecto al diagnóstico (Figura 3). [Conclusión] Las células BiNK procedentes de pacientes con leucemia aguda muestran gran heterogeneidad en la expresión de receptores. Los pacientes con LMA presentan una menor infiltración de células BiNK, así como una escasa capacidad degranulativa en el diagnóstico y recaída de la enfermedad.
- Published
- 2021
34. A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia
- Author
-
Matemáticas, Martínez Rubio, Álvaro, Chulián, Salvador, Blázquez Goñi, Cristina, Ramírez-Orellana, Manuel, Pérez Martínez, Antonio, Navarro Zapata, Alfonso, Ferreras, Cristina, Pérez-García, Víctor M., Rosa Durán, María, Matemáticas, Martínez Rubio, Álvaro, Chulián, Salvador, Blázquez Goñi, Cristina, Ramírez-Orellana, Manuel, Pérez Martínez, Antonio, Navarro Zapata, Alfonso, Ferreras, Cristina, Pérez-García, Víctor M., and Rosa Durán, María
- Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.
- Published
- 2021
35. SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy
- Author
-
Ferreras, C., primary, Pascual-Miguel, B., additional, Mestre-Durán, C., additional, Navarro-Zapata, A., additional, Clares-Villa, L., additional, Martín-Cortázar, C., additional, De Paz, R., additional, Marcos, A., additional, Vicario, J. L., additional, Balas, A., additional, García-Sánchez, F., additional, Eguizabal, C., additional, Solano, C., additional, Mora-Rillo, M., additional, Soria, B., additional, and Pérez-Martínez, A., additional
- Published
- 2021
- Full Text
- View/download PDF
36. Optimizing the Procedure to Manufacture Clinical-Grade NK Cells for Adoptive Immunotherapy
- Author
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Fernández, Adrián, primary, Navarro-Zapata, Alfonso, additional, Escudero, Adela, additional, Matamala, Nerea, additional, Ruz-Caracuel, Beatriz, additional, Mirones, Isabel, additional, Pernas, Alicia, additional, Cobo, Marta, additional, Casado, Gema, additional, Lanzarot, Diego, additional, Rodríguez-Antolín, Carlos, additional, Vela, María, additional, Ferreras, Cristina, additional, Mestre, Carmen, additional, Viejo, Aurora, additional, Leivas, Alejandra, additional, Martínez, Joaquín, additional, Fernández, Lucía, additional, and Pérez-Martínez, Antonio, additional
- Published
- 2021
- Full Text
- View/download PDF
37. A phase II clinical trial of infusing haploidentical K562-mb-IL15-41BBL activated and expanded Natural Killer cells as consolidation therapy for pediatric acute myeloblastic leukemia
- Author
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Jose L. Vicario, Adrián Fernández, José Luis Fuster Soler, Victor Galán, Antonio Pérez-Martínez, Paula Valle, Berta González, Beatriz Ruz, Cristina Ferreras, Lucía Fernández, Antonia Pascual, Isabel Mirones, Jose M. Vagace Valero, Alejandra Leivas, Alfonso Navarro Zapata, Lara Maria Gómez-García, Dolores Corral, Carmen Maestre, Raquel de Paz, Luisa Sisinni, Alberto M. Borobia, Miguel Blanquer Blanquer, Antonio Balas, Joaquin Martinez-Lopez, Adela Escudero, and María Vela
- Subjects
medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Myeloid leukemia ,Gastroenterology ,Confidence interval ,Clinical trial ,Regimen ,Internal medicine ,Cohort ,medicine ,Cumulative incidence ,business ,K562 cells - Abstract
Background. Acute myeloid leukemia (AML) accounts for approximately 25% of pediatric leukemia. The long term overall survival rate now approaches 70%, but up 30% relapse. The anti-leukemia properties of Natural Killer (NK) cells and its safety profile has been reported previously at different phases of AML treatment. We proposed a phase II open, a prospective multicenter, non-randomized clinical trial for adoptive infusion of haploidentical K562-mb15-41BBL activated and expanded Natural Killer (NKAE) cells as a consolidation strategy in children with favorable and intermediate-risk AML who were in first complete remission after chemotherapy (NCT02763475). Previous to NKAE cell infusion, patients received a lymphodepleting regimen. After NKAE cell infusion, patients received low doses (1×106/IU/m2) of IL-2 subcutaneously every 48 hours for 2 weeks. Procedure. Seven patients, median age 7.4 years (range, 0.78–15.98), received 13 infusions of NKAE cells, with a median of 36.44×106 NKAE cells/kg (range, 6.92–193.2×106 cells/kg). Results. Three pair donor-recipient were KIR–HLA-mismatched. Donor KIR haplotype score was better in two cases, and neutral in the rest of the cases. Chimerism was observed in 4 patients median chimerism 0.065%, (range 0.05-0.27%). With a median of follow up of 33 moths, 6 (85.7%) patients remain alive and in complete remission. The 3-year overall survival was 83.3% (95% confidence interval 68.1-98.5), and the 3-year relapse cumulative incidence was 28.6% (95% confidence interval 11.5-45.7). Conclusions. This study shows that NKAE cell infusion as a consolidation strategy was feasible and safe but could not improve the pediatric AML relapse rate in this small cohort.
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- 2020
38. Enfermedad de Iselin, una apofisitis emergente
- Author
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Belenguer Pola,Laura, Borque Navarro,Elena, González Gayán,Laura, and Navarro Zapata,Mª Carmen
- Published
- 2020
39. La anamnesis, un arma muy poderosa para el pediatra
- Author
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Borque Navarro,Elena, Belenguer Pola,Laura, González Gayán,Laura, and Navarro Zapata,Mª Carmen
- Published
- 2020
40. El aprendizaje basado en retos como agente generador de ideas transformadoras en el mundo empresarial
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Alba Ruiz-Morales, Carmen, Navarro Zapata, Estela, and Gómez Cuesta, Laura
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Marketing ,Creatividad ,Aprendizaje activo - Abstract
El reto al que se está enfrentando nuestra sociedad debido al COVID -19 ha puesto en evidencia la importancia y necesidad de competencias como la creatividad, la comunicación y el compromiso ético. Este hecho no debe pasar desapercibido para la comunidad universitaria si verdaderamente, como docentes comprometidos con nuestra labor, queremos asumir la responsabilidad de preparar y formar a nuestros estudiantes para el mundo real. Este artículo pretende describir el proyecto multidisciplinar llevado a cabo durante el curso 2019/2020 en la Universidad Europea y la idoneidad de metodologías como el aprendizaje basado en retos para ayudar a desarrollar, tanto al profesorado como a los estudiantes, las competencias anteriormente señaladas. El proyecto consistió en la reformulación de la tradicional y conocida “Feria de marketing” y su transformación en un reto más complejo: una “Exposición de ideas transformadoras”, donde la creatividad se convirtió en una herramienta transversal, la comunicación oral, escrita y visual en una vía para el éxito y el compromiso ético en la base de cualquier propuesta empresarial. La actividad se llevó a cabo en dos campus distintos al mismo tiempo, con la implicación de diferentes asignaturas en cada uno de ellos, lo que dificultó su diseño, pero resultó tremendamente enriquecedor por los aprendizajes que se pudieron extraer tras la comparación de ambas experiencias. El profesorado que participó en el reto pertenecía a la Facultad de Ciencias Sociales y de la Comunicación e impartía asignaturas dentro de diferentes disciplinas. En el campus de Villaviciosa el proyecto se llevó a cabo dentro de dos grados distintos: el Grado en Marketing y el Grado en Gestión Empresarial basada en el Análisis de Datos, y en el campus de Alcobendas participaron el Grado en Marketing, el Grado en Dirección y Administración de Empresas, y la asignatura de Relaciones públicas y organización de eventos de marketing, perteneciente al segundo curso del Ciclo Formativo de Grado Superior en Marketing y Publicidad. La asunción de roles profesionales y la valoración de las propuestas entre iguales logró extraer del alumnado un mayor compromiso con su propio aprendizaje, además de mostrarles de manera clara y práctica evidencias de la utilidad de los conocimientos adquiridos en el aula, hecho que repercutió de manera positiva en la adquisición de los resultados de aprendizaje y de las competencias curriculares contemplados en cada materia. La medición de la satisfacción del alumnado evidenció su satisfacción tanto con lo aprendido como con la metodología utilizada, animándonos a seguir trabajando y a compartir la experiencia de aprendizaje que se describe en este artículo. Sin financiación No data 2019 UEM
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- 2020
41. Supporting Israel by withholding support to International Organizations: UNRWA and UNESCO in Trump’s foreign policy
- Author
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Estela Navarro Zapata, Alberto Moreno Melgarejo, and Julieta Espín Ocampo
- Subjects
05 social sciences ,Estados Unidos ,General Social Sciences ,Política internacional ,Public administration ,International law ,050601 international relations ,Relaciones Internacionales ,0506 political science ,Politics ,Foreign policy ,Order (business) ,Political science ,Agency (sociology) ,050602 political science & public administration ,Israel ,Administration (government) - Abstract
This paper analyses the steps undertaken by the Trump Administration against UNESCO and UNRWA,the former being a specialized organization, and the latter a specialized agency of the United Nations system, in order to pressure the Palestinian representatives to reach a final peaceagreement with Israel that would go against the basic national aspirations of the Palestinian people and the international law. The article aims to highlight the consequences of this new political approach and how it directly affects the relationship between Palestinians and Israel. El presente artículo analiza los pasos tomados por la Administración Trump en contra de la UNESCO y la UNRWA, la primera, organismo especializado y la segunda agencia especializada del sistema de Naciones Unidas, con el objetivo de presionar a los representantes palestinos para alcanzar un acuerdo de paz con Israel, aún en contra de las aspiraciones básicas del pueblo palestino y del derecho internacional. Asimismo, el artículo pretende mostrar las consecuencias de esta nueva estrategia política y cómo está afectando directamente la relación entre los palestinos e Israel. Sin financiación No data JCR 2020 0.222 SJR (2020) Q3, 309/595 Social Sciences (miscellaneous) 0.375 IDR (2019) C1, 8/85 Ciencias Políticas UEM
- Published
- 2020
42. Me mareo cuando me peinas
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Belenguer Pola,Laura, Borque Navarro,Elena, González Gayán,Laura, and Navarro Zapata,Mª Carmen
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- 2020
43. Neumonías repetidas, ¿buscamos algo más?
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Borque Navarro,Elena, Belenguer Pola,Laura, González Gayán,Laura, and Navarro Zapata,Mª Carmen
- Published
- 2020
44. SARS-CoV-2 specific memory T lymphocytes from COVID-19 convalescent donors: identification, biobanking and large-scale production for Adoptive Cell Therapy
- Author
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Ferreras, C, primary, Pascual-Miguel, B, additional, Mestre-Durán, C, additional, Navarro-Zapata, A, additional, Clares-Villa, L, additional, Martín-Cortázar, C, additional, De Paz, R, additional, Marcos, A, additional, Vicario, JL, additional, Balas, A, additional, García-Sánchez, F, additional, Eguizabal, C, additional, Solano, C, additional, Mora-Rillo, M, additional, Soria, B, additional, and Pérez-Martínez, A, additional
- Published
- 2020
- Full Text
- View/download PDF
45. Donor’s graft ex vivo T‐cell depletion with fludarabine reduces graft‐versus‐host disease signs and improves survival after intestinal transplantation – an experimental study
- Author
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Vela, Maria, primary, Stringa, Pablo, additional, González‐Navarro, Pablo, additional, Machuca, Mariana, additional, Pascual‐Miguel, Bárbara, additional, Mestre, Carmen, additional, Arreola, Nidia M., additional, Papa‐Gobbi, Rodrigo, additional, Navarro‐Zapata, Alfonso, additional, Pires‐Lobo, Sara C., additional, Andrés, Ane M., additional, Hernández‐Oliveros, Francisco, additional, and Pérez‐Martínez, Antonio, additional
- Published
- 2020
- Full Text
- View/download PDF
46. Supporting Israel by Withholding Support from International Organizations: UNRWA and UNESCO in Trump’s Foreign Policy.
- Author
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Espín Ocampo, Julieta, primary, Moreno Melgarejo, Alberto, additional, and Navarro Zapata, Estela, additional
- Published
- 2020
- Full Text
- View/download PDF
47. Estudios sobre la intensidad tecnológica de las exportaciones de manufacturas : análisis general y del caso España-Asia
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Navarro Zapata, Amadeo Fernando
- Abstract
Tesis Doctoral leída en la Universidad Rey Juan Carlos de Madrid en 2019. Directores de la Tesis: María Arrazola Vacas y José de Hevia Payá En los últimos años el estudio de la intensidad tecnológica de las exportaciones de manufacturas ha suscitado gran interés tanto en el ámbito académico como de diseño de la política económica, debido entre otras causas a sus importantes implicaciones sobre el crecimiento económico. Sin embargo, a pesar del creciente interés y de la importancia señalada, los estudios existentes son aún escasos, e incluso inexistentes en el caso de España. Las autoridades españolas en las distintas estrategias de internacionalización de la economía española han puesto el foco en la necesidad de mejorar la intensidad tecnológica de las manufacturas exportadas por las empresas españolas. Asimismo, dichas estrategias enfatizan en la necesidad de mejorar la diversificación geográfica de las exportaciones españolas, caracterizadas por una alta concentración en los países de la UE, y con poca presencia en algunos mercados con gran importancia en el comercio internacional, como es el caso de los mercados asiáticos. Esta tesis aborda estas deficiencias desde diferentes perspectivas que son claves para poder disponer de herramientas que permitan, por una parte a las empresas españolas elaborar planes de expansión hacia nuevos mercados, y por otra parte a las autoridades españolas para diseñar e implementar políticas económicas que favorezcan dichos planes de expansión. El análisis comparativo de las exportaciones de manufacturas españolas, de los principales exportadores de la UE y del resto del mundo a la ASEAN, determina posibles potencialidades para las empresas manufactureras españolas en su procesos de internacionalización en la ASEAN, con especial énfasis en las manufacturas con mayor intensidad tecnológica, para ello se profundiza en aspectos como la complementariedad de los patrones de comercio, la concentración y las ventajas comparativas reveladas. Las competencias sobre la política comercial exterior dentro de la UE, de la cual forma parte España, están en manos de las instituciones comunitarias, por lo tanto, la firma de los tratados comerciales y de libre comercio suscritos por la UE afectan directamente a España. Es por ello que en esta tesis se amplia el análisis de los flujos comerciales de manufacturas España-ASEAN al contexto europeo, y mediante el análisis de variables como el peso del comercio intraindustrial y las ventajas comparativas, se determina que una mayor integración comercial entre ambos bloques podría por una parte consolidar la UE como un importante mercado para la ASEAN, y por otra incrementar las exportaciones de la UE hacia el bloque asiático. Los factores determinantes de la sofisticación tecnológica, de la especialización tecnológica, y del valor total de las manufacturas exportadas con alta intensidad tecnológica por los países de la OCDE, entre los cuales se encuentra España, es otra de las cuestiones importantes que esta tesis aborda. Los resultados del estudio empírico demuestran que entre dichos factores mencionados se encuentran variables como el gasto en I+D, las importaciones de manufacturas con alta intensidad tecnológica, el stock de inversión directa extranjera recibida, la calidad del capital humano, la inversión en capital físico, y el tamaño de la economía exportadora. Esta tesis también analiza el ámbito regional de las exportaciones de manufacturas españolas al mundo y a los países de Asia Oriental, atendiendo a su intensidad tecnológica. Se observa una relación positiva entre la importancia del sector manufacturero en las regiones españolas y el valor total de las exportaciones de manufacturas con alta intensidad tecnológica exportadas. Teniendo en cuenta la importancia de los países de Asia Oriental en los mercados internacionales de manufacturas, se constata que las exportaciones regionales a estos países son mejorables, tanto en términos cuantitativos como cualitativos. El análisis de concentración de las manufacturas exportadas con alto contenido tecnológico por la regiones españolas revela unos índices bajos de concentración, tanto al mundo como a los países de Asia Oriental. El análisis de similitud entre la distribución de manufacturas exportadas de las regiones españolas y la distribución de manufacturas exportadas para el conjunto de España revela que en líneas generales existe un alto grado de similitud, y que dicha similitud se ha homogeneizado con el paso del tiempo. En la última parte de la tesis se realiza un análisis gravitacional de las exportaciones de manufacturas con alta intensidad tecnológica exportadas por España y por la regiones españolas. Los resultados muestran que el tamaño de la economía destino de las exportaciones de manufacturas españolas y los costes asociados son factores determinantes en la localización de dichas manufacturas, con grado de influencia dispar dependiendo de la intensidad tecnológica. El tamaño de la economía regional exportadora, el tamaño de la economía destino de las exportaciones regionales, y los costes asociados a las mismas son factores determinantes en el caso de las exportaciones regionales de manufacturas, aunque su importancia varía según la intensidad tecnológica. Asimismo, los resultados muestran que el tamaño de la economía exportadora es un factor más determinante en las exportaciones de manufacturas regionales con alto contenido tecnológico de aquellas regiones con una renta per cápita superior a la media. No disponer de puerto marítimo afecta negativamente sobre las exportaciones regionales de manufacturas con alto contenido tecnológico. Por último, tener frontera exterior afecta positivamente al volumen de exportaciones regionales de manufacturas con mayor contenido tecnológico.
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- 2019
48. Doctor@, necesito una masterclass para alimentar a mi bebé
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Navarro Zapata, M. C., Borque Navarro, E., Navarro Zapata, M. C., and Borque Navarro, E.
- Abstract
Complementary feeding is an obligatory and periodically reviewed topic in any pediatric treaty. Recommendations change over the years. One of the main activities and competences of the primary care pediatrician in terms of food refers, in addition to promoting breastfeeding, is to advise families and to approach the correct pediatric feeding practices to each age group, offering appropriate recommendations taking into account cultural influences. In our clinics, parents ask us many questions about the right food for their children that I will try to answer in this text based on the latest recommendations., En cualquier tratado pediátrico, la alimentación complementaria es un tema obligado y periódicamente revisado. Por otro lado, las recomendaciones van cambiando a lo largo de los años. Una de las principales actividades y competencias del pediatra de Atención Primaria en lo que a la alimentación se refiere, además de fomentar la lactancia materna, consiste en aconsejar y acercar a las familias las prácticas alimentarias pediátricas correctas para cada grupo de edad, ofreciendo recomendaciones adecuadas que tengan en cuenta las influencias culturales. En nuestras consultas, los padres nos plantean múltiples dudas con respecto a la alimentación adecuada para sus hijos que trataré de responder en este texto apoyándome en las últimas recomendaciones.
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- 2019
49. Mi niño cojea: ¿debo preocuparme?
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Belenguer Pola, L., Borque Navarro, E., Dadlani Dadlani, N., Pestana Gallardo, D., Navarro Zapata, M. C., Belenguer Pola, L., Borque Navarro, E., Dadlani Dadlani, N., Pestana Gallardo, D., and Navarro Zapata, M. C.
- Published
- 2019
50. Explorando en la consulta de Atención Primaria la autoimagen corporal en adolescentes
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Pestana Gallardo, D., Borque Navarro, E., Belenguer Pola, L., Dadlani Dadlani, N., Navarro Zapata, M. C., Pestana Gallardo, D., Borque Navarro, E., Belenguer Pola, L., Dadlani Dadlani, N., and Navarro Zapata, M. C.
- Published
- 2019
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