{"id":59344,"date":"2026-03-21T00:05:57","date_gmt":"2026-03-20T23:05:57","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/21\/co-expression-of-il15-promotes-effector-differentiation-and-sustained-proliferative-capacity-in-alppl2-specific-human-car-t-cells\/"},"modified":"2026-03-21T00:05:57","modified_gmt":"2026-03-20T23:05:57","slug":"co-expression-of-il15-promotes-effector-differentiation-and-sustained-proliferative-capacity-in-alppl2-specific-human-car-t-cells","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/21\/co-expression-of-il15-promotes-effector-differentiation-and-sustained-proliferative-capacity-in-alppl2-specific-human-car-t-cells\/","title":{"rendered":"Co-expression of IL15 promotes effector differentiation and sustained proliferative capacity in ALPPL2-specific human CAR T cells"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Mar 20. doi: 10.1158\/2326-6066.CIR-25-0609. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Chimeric antigen receptor (CAR) T cells have robust antitumor activity against hematologic malignancies and have the potential to benefit patients with solid tumors. Immune recognition of murine proteins expressed in adoptively transferred T cells and lack of homeostatic cytokines in the tumor microenvironment can limit the expansion and persistence of CAR T cells. CARs generated only from human sequences could reduce the risk of immune-mediated rejection and interleukin-15 (IL15), which promotes T-cell survival and fitness, may improve the expansion and persistence of CAR T cells. In this study, we report a CAR construct (ABBz) assembled from human sequences including a single-chain variable fragment (scFv) specific to ALPPL2. This binder was selected through an unbiased, high-throughput screen of a human antibody-derived, phage-displayed scFv library based on binding specificity, stringency, and low dissociation constant. We demonstrated specificity to the antigen, effective cytolytic function, and cytokine production in ABBz T cells. We showed NK-like effector differentiation with sustained proliferative capacity specific to secreted IL15 coexpression in ABBz T cells. Lastly, we demonstrated that ABBz CAR T cells had robust antitumor activity, which was further enhanced through IL15 co-expression, resulting in NK-like effector differentiation with increased cytotoxicity and superior expansion capacity due to reduced apoptosis of CAR T cells. These results demonstrate that IL15 co-expression can promote effector differentiation while maintaining the proliferative capacity of huALPPL2-CAR T cells and provide a foundation for further clinical development of IL15 co-expressing huALPPL2-CAR T cells in patients.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41860794\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260320190556&amp;v=2.19.0.post6+133c1fe\">41860794<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0609\">10.1158\/2326-6066.CIR-25-0609<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Mar 20. doi: 10.1158\/2326-6066.CIR-25-0609. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T cells have robust antitumor activity against hematologic malignancies and have the potential to benefit patients with solid tumors. Immune recognition of murine proteins expressed in adoptively transferred T cells and lack of homeostatic cytokines in the tumor &#8230; <a title=\"Co-expression of IL15 promotes effector differentiation and sustained proliferative capacity in ALPPL2-specific human CAR T cells\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/03\/21\/co-expression-of-il15-promotes-effector-differentiation-and-sustained-proliferative-capacity-in-alppl2-specific-human-car-t-cells\/\" aria-label=\"Read more about Co-expression of IL15 promotes effector differentiation and sustained proliferative capacity in ALPPL2-specific human CAR T cells\">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-59344","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\/59344","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=59344"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/59344\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=59344"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=59344"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=59344"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}