{"id":111795,"date":"2018-03-11T10:38:27","date_gmt":"2018-03-11T10:38:27","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/development-of-immunotherapy-strategies-aimed-at-blocking-the-immunosuppressive-tumor-microenvironment-and-enhance-antitumor-responses\/"},"modified":"2018-03-11T10:38:27","modified_gmt":"2018-03-11T10:38:27","slug":"development-of-immunotherapy-strategies-aimed-at-blocking-the-immunosuppressive-tumor-microenvironment-and-enhance-antitumor-responses","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/inmunologia\/development-of-immunotherapy-strategies-aimed-at-blocking-the-immunosuppressive-tumor-microenvironment-and-enhance-antitumor-responses\/","title":{"rendered":"Development of immunotherapy strategies aimed at blocking the immunosuppressive tumor microenvironment and enhance antitumor responses"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Jos\u00e9 Medina Echeverz <\/strong><\/h2>\n<p>La expresi\u00f3n intratumoral de la prote\u00edna inmunoestimuladora interleuquina 12 (il12) mediante adenovirus permite generar potentes respuestas inmunes antitumorales en distintos modelos tumorales murinos. Sin embargo, la eficacia antitumoral de esta estrategia en un ensayo cl\u00ednico fue muy limitada. Por lo tanto, es necesario nuevas estrategias que, combinadas con la il12, permitan potenciar su eficacia antitumoral en humanos.   la eliminaci\u00f3n de tumores grandes y establecidos requiere la activaci\u00f3n del sistema inmune innato y adaptativo y el bloqueo simult\u00e1neo del sistema inmune regulador. La il12 es un potente activador del sistema inmune innato, desencaden\u00e1ndose una potente respuesta adaptativa. Un trabajo reciente de nuestro laboratorio muestra que, en los hepatocarcinomas que resisten al tratamiento con il12, se acumulan mol\u00e9culas y c\u00e9lulas inmunosupresoras. Por lo tanto, el desarrollo de estrategias que eviten la aparici\u00f3n de este ambiente inmunosupresor inducido por la inmunoterapia pueden ser el complemento necesario para la erradicaci\u00f3n de tumores grandes y establecidos con terapias basadas en la il12.  el microambiente tumoral se compone de distintos tipos celulares que crecen embebidos en el estroma tumoral. Dicho estroma da lugar a las condiciones adecuadas para que los tumores se desarrollen. Entre otras, tgf-beta es una citoquina pleiotr\u00f3pica clave en la biolog\u00eda del tumor presente en el estroma tumoral, y por ello dicha mol\u00e9cula es una diana cl\u00e1sica en inmunoterapia frente al c\u00e1ncer. En el departamento de hepatolog\u00eda y terapia g\u00e9nica del cima se han desarrollado sendos p\u00e9ptidos inhibidores del tgf-beta, p17 y p144, caracterizados in vitro e in vivo en distintos modelos de fibrosis y esclerodermia y se ha probado su eficacia complementando estrategias de vacunaci\u00f3n frente al c\u00e1ncer. Asimismo, p144 recientemente ha entrado en ensayos cl\u00ednicos de fase ii para el tratamiento de la esclerodermia. No obstante, dichos p\u00e9ptidos presentan una vida media corta tras su administraci\u00f3n. Para solventar este problema, en el presente trabajo se vehiculizar\u00e1n los p\u00e9ptidos inhibidores del tgf-beta con el objetivo de aumentar su vida media en el torrente sangu\u00edneo y dirigir dichos p\u00e9ptidos al h\u00edgado.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Development of immunotherapy strategies aimed at blocking the immunosuppressive tumor microenvironment and enhance antitumor responses<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Development of immunotherapy strategies aimed at blocking the immunosuppressive tumor microenvironment and enhance antitumor responses <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Jos\u00e9 Medina Echeverz <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 18\/11\/2011<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Pedro Berraondo L\u00f3pez<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: ignacio javier Melero bermejo <\/li>\n<li>david Sancho Madrid (vocal)<\/li>\n<li> Diaz valdez farray nancy (vocal)<\/li>\n<li>angel Corbi lopez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Jos\u00e9 Medina Echeverz La expresi\u00f3n intratumoral de la prote\u00edna inmunoestimuladora interleuquina 12 (il12) mediante adenovirus permite generar [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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