Development of a Novel Anti-CD19 Chimeric Antigen Receptor : A Paradigm for an Affordable CAR T Cell Production at Academic Institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdc Il2rd/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients

Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at academic institutions

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdcscid Il2rdtm1Wjl/SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Controlling oncogenic KRAS signaling pathways with a Palladium-responsive peptide

RAS oncoproteins are molecular switches associated with critical signaling pathways that regulate cell proliferation and differentiation. Mutations in the RAS family, mainly in the KRAS isoform, are responsible for some of the deadliest cancers, which has made this protein a major target in biomedical research. Here we demonstrate that a designed bis-histidine peptide derived from the αH helix of the cofactor SOS1 binds to KRAS with high affinity upon coordination to Pd(II). NMR spectroscopy and MD studies demonstrate that Pd(II) has a nucleating effect that facilitates the access to the bioactive α-helical conformation. The binding can be suppressed by an external metal chelator and recovered again by the addition of more Pd(II), making this system the first switchable KRAS binder, and demonstrates that folding-upon-binding mechanisms can operate in metal-nucleated peptides. In vitro experiments show that the metallopeptide can efficiently internalize into living cells and inhibit the MAPK kinase cascadeS

Planes de beneficios en salud de América Latina: Una comparación regional

Garantizar el derecho a la salud en igualdad de condiciones para todos es una meta hacia la que toda sociedad quiere avanzar, máxime en una región tan desigual como América Latina y el Caribe. La cobertura universal es un objetivo importante para la mayoría de los países; sin embargo, el contexto para lograr una cobertura universal es difícil: cada día aumenta la presión sobre el gasto en salud. Entonces, ¿qué incluir o no incluir en un plan de beneficios en salud?

TIC dans les techniques de recherche avancées caractérisation et information

Proyecto interfacultativo: Facultad de Ciencias Químicas Facultad de Ciencias Biológicas Facultad de Ciencias Políticas y Sociología Facultad de Ciencias de la Información Centro de Cálculo. Proyecto interdepartamental: Departamento de Química Inorgánica I Departamento de Genética Departamento de Sociología IV Departamento de Comunicación Audiovisual y Publicidad I Departamento Atos-CAU de Ciencias.Se emplean las TIC para describir la información proporcionada por difractogramas, espectros, micrografías, capturas de microscopía y diferentes gráficas obtenidos empleando técnicas avanzadas de caracterización. En un canal creado en YouTube se da difusión del trabajo realizado que se plasma en un conjunto de diez vídeos.TIC are used to describe the information provided by diffractograms, spectra, micrographs, microscope captures and graph differents obtained using advanced characterization techniques. A channel created on YouTube shows the work done which includes a set of ten videos.Les TIC sont utilisées pour décrire les informations fournies par diffractogrammes, spectres, micrographies, microscope et capture graphique and graphiques différents obtenus par l'utilisation de techniques avancées de caractérisation.Un canal créé sur YouTube montre le travail effectué qui comprend une série de dix vidéos.Depto. de Química InorgánicaFac. de Ciencias QuímicasFALSEsubmitte

TIC as a information tool of scientific methodology

Diseño, elaboración y procesado de vídeos en los que se incluye la metodología empleada en una investigación avanzada.Design, development and processing of videos which includes the methodology used in advanced research.Depto. de Química InorgánicaFac. de Ciencias QuímicasFALSEsubmitte

La lectura del territorio como herramienta de proyecto: propuestas de estructura urbana basadas en el soporte territorial.

Presentación de la sesión Premium 4. Ámbito temático: Metrópolis Barcelona, a cargo de Loles Herrero y Sebastià Jornet. Orden de las Ponencias: 1. Objetivos y estrategias para el proyecto territorial de los espacios abiertos metropolitanos: hacia una ecologia regional | Lorena Maristany (Escola Tècnica Superior d'Arquitectura del Vallès). 2. Base territorial para la soberanía alimentaria en la Región Metropolitana de Barcelona | Manel Cunill Llenas (Agraria del Vallés, sccl). 3. Planificación para una gestión dinámica y adaptativa de la infraestructura verde metropolitana: el PEPNat como caso de estudio | Eugenia Vidal (Àrea Metropolitana de Barcelona); Laura Cid (Àrea Metropolitana de Barcelona); Antoni Farrero (Àrea Metropolitana de Barcelona); Patricia García Rodríguez (Àrea Metropolitana de Barcelona); Loles Herrero (Àrea Metropolitana de Barcelona); Kyriaki Ilousi (Àrea Metropolitana de Barcelona); Oriol Monclús (Àrea Metropolitana de Barcelona); Jordi Vila (Àrea Metropolitana de Barcelona). 4. El encaje entre las zonas urbanas y el entorno natural: los espacios fluviales del Área metropolitana de Barcelona | Patricia García Rodríguez (Àrea Metropolitana de Barcelona); José Alonso (Àrea Metropolitana de Barcelona); Laura Cid (Àrea Metropolitana de Barcelona); Antoni Farrero (Àrea Metropolitana de Barcelona); Martín Gullón (Àrea Metropolitana de Barcelona); Kyrian Ilousi (Àrea Metropolitana de Barcelona); Eugenia Vidal Casanovas (Àrea Metropolitana de Barcelona). 5. Modelizando el futuro territorio metropolitano: cálculo de potenciales urbanísticos en la metrópolis de Barcelona | Pere Manubens (Àrea Metropolitana de Barcelona); Laura Bertran (Àrea Metropolitana de Barcelona); Judith Recio (Àrea Metropolitana de Barcelona); Sandra Quesada (Àrea Metropolitana de Barcelona); Javier Alarcón (Àrea Metropolitana de Barcelona). 6. Las necesidades de la población metropolitana desde las tramas residenciales: las dotaciones socioambientales: vivienda, equipamientos y espacios verdes | Alexandra Quesada (Àrea Metropolitana de Barcelona); Mireia Peris (Àrea Metropolitana de Barcelona); Mercè González (Àrea Metropolitana de Barcelona); Elena Castellà (Àrea Metropolitana de Barcelona); Judith Recio (Àrea Metropolitana de Barcelona); Laia Molist (Àrea Metropolitana de Barcelona); Mariona Figueras (Àrea Metropolitana de Barcelona). 7. La participación en la planificación urbanística metropolitana. De la diagnosis compartida a la estrategia participada del Avance del PDU metropolitano | Mireia Peris (Àrea Metropolitana de Barcelona); Joan Caba (Àrea Metropolitana de Barcelona); Laura Ferreres (Àrea Metropolitana de Barcelona); Teresa Gómez Fabra (Àrea Metropolitana de Barcelona); Isabel Tomé (Àrea Metropolitana de Barcelona). 8. La lectura del territorio como herramienta de proyecto: propuestas de estructura urbana basadas en el soporte territorial | Anna Majoral (Àrea Metropolitana de Barcelona); Gavina Corbetta (Àrea Metropolitana de Barcelona); Jordi Peralta (Àrea Metropolitana de Barcelona)