{"id":7952,"date":"2026-04-21T16:00:04","date_gmt":"2026-04-21T23:00:04","guid":{"rendered":"https:\/\/rakuten-med.com\/us\/?post_type=press_releases&#038;p=7952"},"modified":"2026-04-21T01:10:42","modified_gmt":"2026-04-21T08:10:42","slug":"rakuten-medical-presents-new-preclinical-findings-at-aacr-2026-showing-cox-2-inhibition-reduces-photoimmunotherapy-induced-edema-via-pge%e2%82%82-suppression","status":"publish","type":"press_releases","link":"https:\/\/rakuten-med.com\/us\/news\/press-releases\/2026\/04\/21\/7952\/","title":{"rendered":"Rakuten Medical Presents New Preclinical Findings at AACR 2026 Showing COX\u20112 Inhibition Reduces Photoimmunotherapy\u2011Induced Edema via PGE\u2082 Suppression"},"content":{"rendered":"<div id=\"pl-7952\"  class=\"panel-layout\" ><div id=\"pg-7952-0\"  class=\"panel-grid panel-no-style\"  style=\"margin-bottom: 0px\" ><div id=\"pgc-7952-0-0\"  class=\"panel-grid-cell\" ><div id=\"panel-7952-0-0-0\" class=\"so-panel widget widget_sow-editor panel-first-child panel-last-child\" data-index=\"0\" ><div\n\t\t\t\n\t\t\tclass=\"so-widget-sow-editor so-widget-sow-editor-base\"\n\t\t\t\n\t\t>\n<div class=\"siteorigin-widget-tinymce textwidget\">\n\t<ul>\n<li><strong><em>First study showing that post\u2011photoimmunotherapy PGE\u2082 production driven by COX\u20112 activity may contribute to edema formation<\/em><\/strong><\/li>\n<li><strong><em>Findings suggest that prophylactic COX\u20112 inhibition may mitigate edema and improve treatment safety<\/em><\/strong><\/li>\n<\/ul>\n<p><strong>SAN DIEGO <\/strong><strong>\u2014 April 21, 2026 \u2014 <\/strong>Rakuten Medical, Inc., a global biotechnology company developing and commercializing the Alluminox\u00ae platform-based photoimmunotherapy, announces a poster titled \u201c<a href=\"https:\/\/www.abstractsonline.com\/pp8\/#!\/21436\/presentation\/5131\" target=\"_blank\" rel=\"noopener\">COX-2\/PGE2 driven, photoimmunotherapy-induced edema is reduced by prophylactic NSAIDs in mouse tumor models<\/a>\u201d was presented today at the 2026 Annual Meeting of the American Association for Cancer Research (AACR 2026) in San Diego. The poster examined the mechanism underlying photoimmunotherapy-induced edema and the potential of cyclooxygenase\u20112 (COX\u20112) inhibition to reduce edema.<\/p>\n<p>COX\u20112 is an inducible enzyme that is upregulated under inflammatory conditions. Previous mouse studies by Rakuten Medical showed that <a href=\"https:\/\/rakuten-med.com\/us\/news\/press-releases\/2024\/04\/11\/7834\/\">prophylactic selective COX\u20112 inhibition reduced the volume of photoimmunotherapy-induced edema by 30\u201350%<\/a>.<\/p>\n<p>In this AACR poster presentation, induction of COX\u20112 expression and secretion of prostaglandin E\u2082 (PGE\u2082) were observed following photoimmunotherapy. While co\u2011incubation with either a selective COX\u20112 inhibitor or a pan\u2011COX inhibitor did not suppress COX\u20112 expression, PGE\u2082 secretion was blocked by these agents. PGE\u2082 is known to be produced predominantly via COX\u20112 activity under inflammatory conditions and to contribute to edema formation by increasing vascular permeability. Importantly, in the mouse tumor models evaluated here, COX inhibition did not affect anti-tumor efficacy.<\/p>\n<p>Collectively, these results suggest that photoimmunotherapy\u2011induced edema is mediated by induction of COX\u20112 expression followed by COX\u20112 activity-dependent PGE\u2082 production; also, prophylactic COX\u20112 inhibition may allow better management of edema.<\/p>\n<p>Photoimmunotherapy based on Rakuten Medical\u2019s proprietary Alluminox platform involves the administration of a drug that selectively binds to target cells, followed by laser illumination that has been shown in the preclinical setting to rapidly and selectively disrupt the cell membrane of the targeted cells. From early clinical studies<sup>1<\/sup> and from real-world clinical use in Japan<sup>2<\/sup> in head and neck cancer, photoimmunotherapy with ASP-1929 suggests that the safety profile may be manageable: of note, edema is a commonly reported adverse event, and in cases where tongue swelling or laryngeal edema poses a risk of airway obstruction, prophylactic interventions such as tracheostomy may be required. These measures can place a significant burden on patients, underscoring the need for less invasive approaches to edema management.<\/p>\n<p><em>Disclaimer: Rakuten Medical\u2019s photoimmunotherapy is investigational outside Japan.<\/em><\/p>\n<p>Strategies to manage photoimmunotherapy\u2011induced edema are being evaluated in real\u2011world settings through a multicenter investigator\u2011initiated study in Japan. Based on the findings of this preclinical study and ongoing clinical research, Rakuten Medical continues to evaluate safety, with aims to optimize the safety of its Alluminox platform and better manage patient burden.<\/p>\n<p><span style=\"text-decoration: underline\"><b>Key findings presented at AACR 2026<\/b><\/span><\/p>\n<p><b>Title: COX-2\/PGE<sub>2<\/sub> driven, photoimmunotherapy-induced edema is reduced by prophylactic NSAIDs in mouse tumor models<\/b><\/p>\n<p><span style=\"font-weight: 400\">Poster Link: <\/span><span style=\"font-weight: 400\"><a href=\"https:\/\/rakuten-med.com\/us\/wp-content\/uploads\/sites\/6\/2026\/04\/Amantea-4297-AACR-2026-poster.pdf\">View\/Download Poster [PDF]<\/a><\/span><\/p>\n<p><span style=\"font-weight: 400\">Abstract Number: 4297<\/span><\/p>\n<p><span style=\"font-weight: 400\">Abstract Link: <\/span><a href=\"https:\/\/www.abstractsonline.com\/pp8\/#!\/21436\/presentation\/5131\" target=\"_blank\" rel=\"noopener\"><span style=\"font-weight: 400\">https:\/\/www.abstractsonline.com\/pp8\/#!\/21436\/presentation\/5131<\/span><\/a><\/p>\n<ul>\n<li><em>In vitro<\/em>, Ephrin A2 (EphA2)-expressing CT26 and LL2 tumor models were incubated with an anti\u2011EphA2-IR700 conjugate \u00b1 light, and COX\u20112 expression was assessed by real\u2011time PCR and Western blot, showing increased expression following photoimmunotherapy light illumination.<\/li>\n<li>Co\u2011incubation with the selective COX\u20112 inhibitor robenacoxib or the pan\u2011COX inhibitor flurbiprofen did not suppress post\u2011photoimmunotherapy COX\u20112 expression.<\/li>\n<li>ELISA analysis revealed immediate post\u2011photoimmunotherapy induction of PGE\u2082 secretion, which was completely blocked by COX inhibition.<\/li>\n<li><em>In vivo<\/em>, photoimmunotherapy\u2011induced edema peaked six hours post\u2011photoimmunotherapy in CT26\u2011EphA2 and LL2\u2011EphA2 mouse tumor models.<\/li>\n<li>Prophylactic treatment with either COX inhibitor significantly reduced edema (p \u22640001).<\/li>\n<li>COX\u20112 expression was increased post\u2011photoimmunotherapy in tumor lysates, while COX\u20111 expression was unchanged and unaffected by COX inhibition.<\/li>\n<li>Elevated circulating PGE\u2082 metabolites post\u2011photoimmunotherapy were observed <em>in vivo <\/em>and were abrogated by COX inhibition.<\/li>\n<li>In a human hypopharyngeal cancer xenograft model, edema similarly peaked at six hours post\u2011photoimmunotherapy and was significantly reduced by prophylactic COX inhibition (p \u22640001).<\/li>\n<li>No compromise in photoimmunotherapy-induced antitumor efficacy was observed with COX inhibitor treatment.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<ol style=\"font-size: 0.8em\">\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Cognetti DM, Johnson JM, Curry JM, et al. Phase 1\/2a, open\u2011label, multicenter study of RM\u20111929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma. Head Neck. 2021;43(12):3875\u20133887. doi:10.1002\/hed.26885<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">Shinozaki T, et al. Real\u2011world clinical experience with ASP\u20111929 photoimmunotherapy in head and neck cancer. 34th Annual Meeting of the Japanese Society for Head and Neck Surgery; January 2025.<\/span><\/li>\n<\/ol>\n<\/div>\n<\/div><\/div><\/div><\/div><div id=\"pg-7952-1\"  class=\"panel-grid panel-no-style\"  style=\"margin-bottom: 0px\" ><div id=\"pgc-7952-1-0\"  class=\"panel-grid-cell\" ><div id=\"panel-7952-1-0-0\" class=\"so-panel widget widget_sow-editor panel-first-child panel-last-child\" data-index=\"1\" ><div class=\"panel-widget-style panel-widget-style-for-7952-1-0-0\" ><div\n\t\t\t\n\t\t\tclass=\"so-widget-sow-editor so-widget-sow-editor-base\"\n\t\t\t\n\t\t>\n<div class=\"siteorigin-widget-tinymce textwidget\">\n\t<p><b>About Rakuten Medical, Inc.<br \/>\n<\/b><span style=\"font-weight: 400\">Rakuten Medical, Inc. is a global biotechnology company developing and commercializing Alluminox\u00ae platform-based photoimmunotherapy, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing. Rakuten Medical\u2019s photoimmunotherapy is currently investigational outside Japan. Rakuten Medical is committed to its mission to conquer cancer by developing its pioneering treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 5 countries\/regions, including the United States, where it is headquartered, Japan, Taiwan, Switzerland and India. For more information, visit <\/span><a href=\"http:\/\/www.rakuten-med.com\"><span style=\"font-weight: 400\">www.rakuten-med.com<\/span><\/a><span style=\"font-weight: 400\">.\u00a0<\/span><\/p>\n<p><b>About Alluminox\u00ae platform<br \/>\n<\/b><span style=\"font-weight: 400\">The Alluminox\u00ae platform is Rakuten Medical\u2019s investigational technology platform that combines pharmaceuticals, medical devices, medical technology, and other peripheral technologies. Rakuten Medical is developing Alluminox platform-based photoimmunotherapy, which involves two key steps: 1) drug administration and 2) targeted illumination using medical devices. The drug component consists of a cell-targeting moiety conjugated to a light-activatable dye, such as IRDye\u00ae 700DX (IR700), that selectively binds to the surface of targeted cells, such as tumor cells. The device component consists of a light source that locally illuminates the targeted cells with red light (690nm) to transiently activate the drug. Rakuten Medical\u2019s pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted tumor cells and\/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Photoimmunotherapy was originally developed by Dr. Hisataka Kobayashi and his team at the National Cancer Institute in the United States. Outside Japan, Rakuten Medical\u2019s Alluminox platform-based photoimmunotherapy is investigational.\u00a0<\/span><\/p>\n<p><b>Media &amp; Investor Contact:<br \/>\n<\/b><span style=\"font-weight: 400\">Ai Yoshikawa<br \/>\n<\/span><span style=\"font-weight: 400\">Associate Director, Global Corporate Communications &amp; Investor Relations<br \/>\n<\/span><span style=\"font-weight: 400\">Tel: +81-(0)70-4196-0845<br \/>\n<\/span><span style=\"font-weight: 400\">Email: <\/span><a href=\"mailto:ai.yoshikawa@rakuten-med.com\"><span style=\"font-weight: 400\">ai.yoshikawa@rakuten-med.com<\/span><\/a><\/p>\n<\/div>\n<\/div><\/div><\/div><\/div><\/div><div id=\"pg-7952-2\"  class=\"panel-grid panel-no-style\" ><div id=\"pgc-7952-2-0\"  class=\"panel-grid-cell\" ><div id=\"panel-7952-2-0-0\" class=\"so-panel widget widget_sow-button panel-first-child panel-last-child\" data-index=\"2\" ><div style=\"padding: 30px 0px 0px 0px;\" class=\"panel-widget-style panel-widget-style-for-7952-2-0-0\" ><div\n\t\t\t\n\t\t\tclass=\"so-widget-sow-button so-widget-sow-button-flat-6fd36f18507f-7952\"\n\t\t\t\n\t\t><div class=\"ow-button-base ow-button-align-center\"\n>\n\t\t\t<a\n\t\t\t\t\thref=\"https:\/\/rakuten-med.com\/us\/contact\/\"\n\t\t\t\t\tclass=\"rakuten-btn sowb-button ow-icon-placement-left ow-button-hover\" \t>\n\t\t<span>\n\t\t\t\n\t\t\tContact Us\t\t<\/span>\n\t\t\t<\/a>\n\t<\/div>\n<\/div><\/div><\/div><\/div><\/div><\/div>","protected":false},"excerpt":{"rendered":"<p>First study showing that post\u2011photoimmunotherapy PGE\u2082 production driven by COX\u20112 activity may contribute to edema formation Findings suggest that prophylactic [&hellip;]<\/p>\n","protected":false},"author":4,"featured_media":0,"template":"","meta":{"_acf_changed":false,"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":""},"class_list":{"0":"post-7952","1":"press_releases","2":"type-press_releases","3":"status-publish","5":"entry"},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - 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