{"id":38,"date":"2021-11-03T00:03:50","date_gmt":"2021-11-03T00:03:50","guid":{"rendered":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue1\/?p=38"},"modified":"2022-08-02T12:02:08","modified_gmt":"2022-08-02T12:02:08","slug":"mogamulizumab-mechanism-of-action-and-measuring-the-response-to-treatment","status":"publish","type":"post","link":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/mogamulizumab-mechanism-of-action-and-measuring-the-response-to-treatment\/","title":{"rendered":"Mogamulizumab mechanism of action and measuring the response to treatment"},"content":{"rendered":"<p>Interview and article by Christine Clark, PhD, FRPharmS.<\/p>\n<p>Mogamulizumab is a humanised monoclonal antibody that selectively binds to C-C chemokine receptor 4 (CCR4). CCR4 is involved in trafficking of lymphocytes to skin and is expressed on the surface of tumour cells in certain T-cell malignancies.<\/p>\n<p><!--more--><\/p>\n<p>When mogamulizumab is used to treat cutaneous T-cell lymphoma (CTCL) the response is usually monitored by assessment of all four affected anatomical compartments \u2013 skin, lymph nodes, viscera and blood.<\/p>\n<p>Mogamulizumab is an antibody that selectively binds to CCR4<sup>1<\/sup>\u00a0and elicits anti-tumour activity by antibody-dependent cellular cytotoxicity (ADCC).<sup>2<\/sup>\u00a0CCR4 in association with its ligands \u2013 the chemokines thymus- and activation-regulated chemokine (TARC, CCL17) and macrophage-derived chemokine (MDC, CCL22)<sup>3<\/sup>\u00a0\u2013 is involved in the trafficking of T-cells to the skin as part of normal immunosurveillance.<sup>4,5<\/sup>\u00a0In CTCL it is also involved in the trafficking of skin-homing neoplastic T-cells, leading to local immune responses and skin manifestations.<sup>5<\/sup><\/p>\n<p>CCR4 is also expressed on T-regulatory (Treg) cells and mogamulizumab-induced depletion of T-reg cells<sup>6<\/sup> may also contribute to the overall anti-tumour effects.<\/p>\n<p><strong>Assessing response<\/strong><br \/>\nProfessor Pablo Ortiz-Romero (Dermatology Department, Hospital 12 de Octubre Medical School, Madrid Spain) describes how the response to treatment is monitored:<\/p>\n<p><iframe loading=\"lazy\" title=\"Article 5 - Ortiz #1\" src=\"https:\/\/player.vimeo.com\/video\/641728124?dnt=1&amp;app_id=122963\" width=\"500\" height=\"281\" frameborder=\"0\" allow=\"autoplay; fullscreen; picture-in-picture; clipboard-write\"><\/iframe><\/p>\n<p>The response to treatment is measured using disease-specific international consensus guidelines<sup>7<\/sup>\u00a0by assessment of all four affected anatomical compartments \u2013 skin, lymph nodes, viscera and blood.<br \/>\nThe skin response is measured using the mSWAT (modified severity weighted assessment tool) that takes account of the percentage of body surface area affected and the type and severity of lesions. This \u201ctranslates into numbers \u2026 what the patient has on the skin\u201d on a scale from 0 to 400, says Professor Ortiz. Peripheral blood is assessed using flow cytometry. Lymph node and visceral involvement is assessed by CT scan or PET-CT scan.<\/p>\n<p><span style=\"font-size: 10pt;\">References<\/span><\/p>\n<ol>\n<li><span style=\"font-size: 10pt;\">Potiligeo (mogamulizumab) Summary of Product Characteristics<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Kim YH et al Lancet 2018;19:1192-1204<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Yoshie O &amp; Matsushima K. CCR4 and its ligands: from bench to bedside. Int Immunol. 2015 Jan;27(1):11-20. doi: 10.1093\/intimm\/dxu079.<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Ferenczi K et al J Invest Dermatol 2002;119:1405-1410<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Girardi M et al. N Engl J Med2004;350:1978-1988<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Ni X et al. Clin Cancer Res. 2015;21:274-85. \u00a0doi: 10.1158\/1078-0432.CCR-14-0830<\/span><\/li>\n<li><span style=\"font-size: 10pt;\">Olsen EA et al. J Clin Oncol 2011;29:2598-2607<\/span><\/li>\n<\/ol>\n<p>&nbsp;<\/p>\n<p><a href=\"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/\">Back to homepage -&gt;<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Interview and article by Christine Clark, PhD, FRPharmS. Mogamulizumab is a humanised monoclonal antibody that selectively binds to C-C chemokine receptor 4 (CCR4). CCR4 is involved in trafficking [&hellip;]<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-38","post","type-post","status-publish","format-standard","hentry","category-in-this-issue"],"acf":[],"_links":{"self":[{"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/posts\/38","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/comments?post=38"}],"version-history":[{"count":18,"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/posts\/38\/revisions"}],"predecessor-version":[{"id":141,"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/posts\/38\/revisions\/141"}],"wp:attachment":[{"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/media?parent=38"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/categories?post=38"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.medicalupdateonline.com\/conferenceconnectissue02101\/wp-json\/wp\/v2\/tags?post=38"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}