The success of T-cell therapies for solid tumors has been limited, among others, by the scarcity of tumor-specific targets. To better understand how successful T-cell responses induced by immune checkpoint blockade (ICB) eliminate metastatic tumors, we conducted a longitudinal landscape analysis of the neoepitope-specific T cells during treatment in patients with melanoma with and without response to ICB. We characterized the target of the T-cell responses and their evolution over time in peripheral blood and tumor. In these studies, we showed that all patients presented neoantigen-specific T-cell responses that were tumor-reactive and targeted a limited number of immunodominant epitopes. Interestingly, in patients with clinical benefit from ICB, these responses were polyclonal, with multiple TCR clonotypes specific for the same mutations, and recurrently detected over time.
\nAlternatively, a promising therapeutic option for patients without response to ICB is adoptive T-cell therapy with T cells genetically modified to target shared antigens. We propose targeting the surface expression of TYRP1 to treat cutaneous and rare subtypes of melanoma. Using a fine-tuning engineering approach, we developed a highly-sensitive CAR-T cell therapy that detects the low amounts of TYRP1 localized on the cell surface. The TYRP1 CAR-T cell therapy presents robust antitumor activity without toxicity in murine and patient-derived cutaneous, acral, and uveal melanoma models. Based on this efficacy and safety profile, we are currently planning the phase I clinical trial.<\/p>\n
Hosted by Ramon Alemany – Cancer Immunotherapy group<\/em><\/p>\n","protected":false},"featured_media":23795,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"default","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":"default","adv-header-id-meta":"","stick-header-meta":"default","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":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}}},"tags":[78],"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/agenda\/23793"}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/agenda"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/agenda"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/23795"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=23793"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=23793"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}