{"id":56290,"date":"2026-02-13T19:08:08","date_gmt":"2026-02-13T18:08:08","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/02\/13\/wtx-124-a-conditionally-activated-wild-type-il2-maximizes-the-therapeutic-index-of-il2-unlike-non-alpha-muteins\/"},"modified":"2026-02-13T19:08:08","modified_gmt":"2026-02-13T18:08:08","slug":"wtx-124-a-conditionally-activated-wild-type-il2-maximizes-the-therapeutic-index-of-il2-unlike-non-alpha-muteins","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/02\/13\/wtx-124-a-conditionally-activated-wild-type-il2-maximizes-the-therapeutic-index-of-il2-unlike-non-alpha-muteins\/","title":{"rendered":"WTX-124, a Conditionally Activated Wild-Type IL2, Maximizes the Therapeutic Index of IL2, Unlike “Non-Alpha” Muteins"},"content":{"rendered":"
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Cancer Immunol Res<\/b>. 2026 Feb 13:OF1-OF16. doi: 10.1158\/2326-6066.CIR-25-0558. Online ahead of print.<\/p>\n

ABSTRACT<\/b><\/p>\n

High-dose interleukin 2 (HD IL2) produces durable responses in patients with advanced cancer, but its use is limited by life-threatening toxicities such as vascular leak syndrome (VLS). To improve the therapeutic index for IL2, a class of IL2 molecules has been engineered to not bind the alpha subunit (CD25) of the high-affinity IL2 receptor. Although these “non-alpha” muteins do not cause VLS, they have other dose-limiting toxicities and have yet to demonstrate antitumor activity comparable with HD IL2. We therefore investigated the potential of a tumor-activated, wild-type IL2 molecule (WTX-124) to improve IL2 tolerability without compromising its efficacy. In mouse models, CD25 engagement by wild-type IL2 was required for optimal activation of tumor-specific CD8+ T cells and for antitumor efficacy. Furthermore, wild-type IL2 was nearly 100-fold more potent than non-alpha IL2 in activating primary human tumor-infiltrating lymphocytes (TIL), even with FoxP3+ regulatory T cells present. Pharmacokinetic-receptor occupancy (PK\/RO) modeling showed that by masking wild-type IL2 in the periphery, WTX-124 produces high RO on TILs but low RO on peripheral lymphocytes, unlike non-alpha IL2s. These findings therefore identify the conditional activation of wild-type IL2 as a promising engineering strategy to improve IL2 tolerability without compromising its antitumor activity.<\/p>\n

PMID:41685778<\/a> | DOI:10.1158\/2326-6066.CIR-25-0558<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

Cancer Immunol Res. 2026 Feb 13:OF1-OF16. doi: 10.1158\/2326-6066.CIR-25-0558. Online ahead of print. ABSTRACT High-dose interleukin 2 (HD IL2) produces durable responses in patients with advanced cancer, but its use is limited by life-threatening toxicities such as vascular leak syndrome (VLS). To improve the therapeutic index for IL2, a class of IL2 molecules has been engineered … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-56290","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/56290","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=56290"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/56290\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=56290"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=56290"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=56290"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}