{"id":38782,"date":"2025-07-23T17:47:52","date_gmt":"2025-07-23T15:47:52","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/07\/23\/an-il-15-modified-nkp30xher2-trispecific-nk-cell-engager-enhances-nk-cell-activation-and-tumor-cell-killingyaping-cheng-on-22-de-july-de-2025-at-1000\/"},"modified":"2025-07-23T17:47:52","modified_gmt":"2025-07-23T15:47:52","slug":"an-il-15-modified-nkp30xher2-trispecific-nk-cell-engager-enhances-nk-cell-activation-and-tumor-cell-killingyaping-cheng-on-22-de-july-de-2025-at-1000","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/07\/23\/an-il-15-modified-nkp30xher2-trispecific-nk-cell-engager-enhances-nk-cell-activation-and-tumor-cell-killingyaping-cheng-on-22-de-july-de-2025-at-1000\/","title":{"rendered":"An IL-15-modified NKp30\u00d7HER2 trispecific NK cell engager enhances NK cell activation and tumor cell killing\u200bYaping Cheng   on 22 de July de 2025 at 10:00"},"content":{"rendered":"<div>\n<p><b>J Leukoc Biol<\/b>. 2025 Jul 22:qiaf107. doi: 10.1093\/jleuko\/qiaf107. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Natural killer (NK) cells represent a promising effector population for tumor immunotherapy. Conventional NK cell engagers (NKCEs), primarily targeting CD16a, show efficacy but face limitations due to receptor polymorphisms and off-target toxicity. Here, we report the development and characterization of a novel trispecific NK cell engager (TriKE) simultaneously targeting the activating receptor NKp30 and the tumor-associated antigen HER2, integrated with a modified interleukin-15 (IL-15 N72D) fused to the IL-15R\u03b1 sushi domain (IL-15R\u03b1Su) to enhance NK cell proliferation and persistence. Protein expression and affinity analyses confirmed the proper formation of the fusion protein with high-affinity binding to NKp30, HER2, and IL-15 receptor components. Flow cytometry demonstrated dose-dependent binding of the TriKE to primary human NK cells and HER2+ tumor cells. Functionally, the TriKE induced significantly greater NK cell activation, as measured by CD69 expression, compared to a bispecific engager lacking IL-15. Importantly, cytotoxicity assays revealed superior NK-mediated killing of HER2+ tumor cells upon prolonged exposure, highlighting the immunostimulatory effect of the IL-15 moiety. These results establish the \u03b1NKp30 TriKE as a potent platform to redirect NK cytotoxicity against HER2+ tumors, combining targeted receptor engagement with cytokine-driven activation to enhance NK cell-based cancer immunotherapy.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40694640\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=8405628&amp;ff=20250723114750&amp;v=2.18.0.post9+e462414\">40694640<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jleuko\/qiaf107\">10.1093\/jleuko\/qiaf107<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Leukoc Biol. 2025 Jul 22:qiaf107. doi: 10.1093\/jleuko\/qiaf107. Online ahead of print. ABSTRACT Natural killer (NK) cells represent a promising effector population for tumor immunotherapy. Conventional NK cell engagers (NKCEs), primarily targeting CD16a, show efficacy but face limitations due to receptor polymorphisms and off-target toxicity. Here, we report the development and characterization of a novel &#8230; <a title=\"An IL-15-modified NKp30\u00d7HER2 trispecific NK cell engager enhances NK cell activation and tumor cell killing\u200bYaping Cheng   on 22 de July de 2025 at 10:00\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/07\/23\/an-il-15-modified-nkp30xher2-trispecific-nk-cell-engager-enhances-nk-cell-activation-and-tumor-cell-killingyaping-cheng-on-22-de-july-de-2025-at-1000\/\" aria-label=\"Read more about An IL-15-modified NKp30\u00d7HER2 trispecific NK cell engager enhances NK cell activation and tumor cell killing\u200bYaping Cheng   on 22 de July de 2025 at 10:00\">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":[86,42],"tags":[],"class_list":["post-38782","post","type-post","status-publish","format-standard","hentry","category-journal-of-leukocyte-biology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/38782","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=38782"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/38782\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=38782"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=38782"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=38782"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}