{"id":5015,"date":"2023-03-10T09:15:25","date_gmt":"2023-03-10T08:15:25","guid":{"rendered":"https:\/\/ibb.uab.cat\/?p=5015"},"modified":"2023-03-10T09:15:25","modified_gmt":"2023-03-10T08:15:25","slug":"nanobiotechnology-t22-pe24-h6-nanotoxin-selectively-kills-cxcr4-high-expressing-aml-patient-cells-in-vitro-and-potently-blocks-dissemination-in-vivo","status":"publish","type":"post","link":"https:\/\/ibb.uab.cat\/index.php\/2023\/03\/10\/nanobiotechnology-t22-pe24-h6-nanotoxin-selectively-kills-cxcr4-high-expressing-aml-patient-cells-in-vitro-and-potently-blocks-dissemination-in-vivo\/","title":{"rendered":"Nanobiotechnology: \u201cT22-PE24-H6 Nanotoxin Selectively Kills CXCR4-High Expressing AML Patient Cells In Vitro and Potently Blocks Dissemination In Vivo&#8221;"},"content":{"rendered":"\n<p><em>Pharmaceutics<\/em>\u00a0<strong>2023<\/strong>,\u00a0<em>15<\/em>(3), 727;\u00a0<a href=\"https:\/\/doi.org\/10.3390\/pharmaceutics15030727\">https:\/\/doi.org\/10.3390\/pharmaceutics15030727<\/a><\/p>\n\n\n\n<h2 id=\"html-abstract-title\">Abstract<\/h2>\n\n\n\n<div class=\"wp-block-image is-style-default\"><figure class=\"alignright is-resized\"><img loading=\"lazy\" src=\"https:\/\/pub.mdpi-res.com\/pharmaceutics\/pharmaceutics-15-00727\/article_deploy\/html\/images\/pharmaceutics-15-00727-ag-550.jpg?1677055639\" alt=\"\" width=\"-53\" height=\"-40\"\/><\/figure><\/div>\n\n\n\n<p>Despite advances in the development of targeted therapies for acute myeloid leukemia (AML), most patients relapse. For that reason, it is still necessary to develop novel therapies that improve treatment effectiveness and overcome drug resistance. We developed T22-PE24-H6, a protein nanoparticle that contains the exotoxin A from the bacterium\u00a0<em>Pseudomonas aeruginosa<\/em>\u00a0and is able to specifically deliver this cytotoxic domain to CXCR4<sup>+<\/sup>\u00a0leukemic cells. Next, we evaluated the selective delivery and antitumor activity of T22-PE24-H6 in CXCR4<sup>+<\/sup>\u00a0AML cell lines and BM samples from AML patients. Moreover, we assessed the in vivo antitumor effect of this nanotoxin in a disseminated mouse model generated from CXCR4<sup>+<\/sup>\u00a0AML cells. T22-PE24-H6 showed a potent, CXCR4-dependent antineoplastic effect in vitro in the MONO-MAC-6 AML cell line. In addition, mice treated with nanotoxins in daily doses reduced the dissemination of CXCR4<sup>+<\/sup>\u00a0AML cells compared to buffer-treated mice, as shown by the significant decrease in BLI signaling. Furthermore, we did not observe any sign of toxicity or changes in mouse body weight, biochemical parameters, or histopathology in normal tissues. Finally, T22-PE24-H6 exhibited a significant inhibition of cell viability in CXCR4<sup>high<\/sup>\u00a0AML patient samples but showed no activity in CXCR4<sup>low<\/sup>\u00a0samples. These data strongly support the use of T22-PE24-H6 therapy to benefit high-CXCR4-expressing AML patients.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Pharmaceutics\u00a02023,\u00a015(3), 727;\u00a0https:\/\/doi.org\/10.3390\/pharmaceutics15030727 Abstract Despite advances in the development of targeted therapies for acute myeloid leukemia (AML), most patients relapse. For that reason, it is still necessary to develop novel therapies that improve treatment effectiveness and overcome drug resistance. We developed T22-PE24-H6, a protein nanoparticle that contains the exotoxin A from the bacterium\u00a0Pseudomonas aeruginosa\u00a0and is able [&hellip;]<\/p>\n","protected":false},"author":65,"featured_media":5016,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[4],"tags":[],"_links":{"self":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/5015"}],"collection":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/comments?post=5015"}],"version-history":[{"count":1,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/5015\/revisions"}],"predecessor-version":[{"id":5017,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/posts\/5015\/revisions\/5017"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media\/5016"}],"wp:attachment":[{"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/media?parent=5015"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/categories?post=5015"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ibb.uab.cat\/index.php\/wp-json\/wp\/v2\/tags?post=5015"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}