{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T03:39:46Z","timestamp":1793936386901,"version":"4.8.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF21OC0066562"],"award-info":[{"award-number":["NNF21OC0066562"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"Kr\u00e6ftens Bek\u00e6mpelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011958","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Adoptive cell therapy (ACT) has shown promising results in cancer treatment, however, achieving effective ex vivo expansion of potent, functionally active, and cytotoxic T cells remains challenging. To address this challenge, we recently developed artificial antigen-presenting scaffolds (Ag-scaffolds) capable of expanding antigen-specific T cells with phenotypes favorable for ACT.  Here, we compared the established technology using IL2\/IL21-loaded Ag-scaffolds (Ag-IL2\/21) with scaffolds incorporating Neoleukin-2\/15 (Ag-Neo2\/15), an engineered cytokine that selectively signals via IL-2R\u03b2\/\u03b3 complexes to enhance CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell proliferation while limiting regulatory T cell expansion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Antigen-specific T cells were expanded ex vivo using Ag-IL2\/21 or Ag-Neo2\/15 scaffolds. Expansion efficiency, cytokine production, and cytotoxic activity were assessed. Functional and transcriptional states were profiled using single-cell sequencing, including cytotoxic and dysfunction gene signature scoring. T cell receptor (TCR) sequencing was performed to evaluate clonal expansion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ag-Neo2\/15 scaffolds supported robust expansion of antigen-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells at levels comparable to Ag-IL2\/21 scaffolds. Ag-Neo2\/15-expanded CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells exhibited increased effector cytokine production and durable cytotoxicity against tumor cells. Single-cell transcriptomic analysis revealed higher cytotoxic gene signature scores, reduced dysfunctional scores, and increased expression of genes linked to increased proliferation in Ag-Neo2\/15-expanded T cells. TCR sequencing demonstrated preferential expansion of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell clones enriched for transcriptional features associated with antigen-experienced effector states and sustained effector function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Ag-Neo2\/15 scaffolds enhance the quality of\n                      <jats:italic>ex vivo<\/jats:italic>\n                      -expanded antigen-specific T cells by promoting a cytotoxic, less dysfunctional, and highly proliferative phenotype. These findings identify Ag-Neo2\/15 as a promising improvement for ACT manufacturing, optimizing the balance between expansion capacity and durable effector function, with potential implications for improving cancer immunotherapy outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1804678","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:46:46Z","timestamp":1781156806000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Antigen-scaffolds loaded with hyper-stable neoleukin-2\/15 expand antigen-specific T cells with a favorable phenotype for adoptive cell therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Maria","family":"Ormh\u00f8j","sequence":"first","affiliation":[{"name":"Experimental and Translational Immunology, Department for Health Technology, Technical University of Denmark","place":["Kongens Lyngby, Denmark"]},{"name":"Biotechnology, Department of Green Technology, University of Southern Denmark","place":["Odense, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamilla Kj\u00e6rgaard","family":"Munk","sequence":"additional","affiliation":[{"name":"Experimental and Translational Immunology, Department for Health Technology, Technical University of Denmark","place":["Kongens Lyngby, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri","family":"Tvingsholm","sequence":"additional","affiliation":[{"name":"Experimental and Translational Immunology, Department for Health Technology, Technical University of Denmark","place":["Kongens Lyngby, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keerthana","family":"Ramanathan","sequence":"additional","affiliation":[{"name":"Experimental and Translational Immunology, Department for Health Technology, Technical University of Denmark","place":["Kongens Lyngby, 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Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigorii","family":"Nos","sequence":"additional","affiliation":[{"name":"Experimental and Translational Immunology, Department for Health Technology, Technical University of Denmark","place":["Kongens Lyngby, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tripti","family":"Tamhane","sequence":"additional","affiliation":[{"name":"Experimental and Translational Immunology, Department for Health Technology, Technical University of Denmark","place":["Kongens Lyngby, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00f3lmfridur R\u00f3sa","family":"Halld\u00f3rsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"Experimental and Translational Immunology, Department for Health Technology, Technical University of Denmark","place":["Kongens Lyngby, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren 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