{"id":57496,"date":"2026-03-04T14:08:10","date_gmt":"2026-03-04T13:08:10","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/04\/her2-specific-synthetic-antigen-receptor-sar-t-cell-therapy-synergizes-with-radiotherapy-to-provide-improved-anti-tumor-efficacy-in-non-small-cell-lung-cancer-nsclcolga-demetra-biziotis\/"},"modified":"2026-03-04T14:08:10","modified_gmt":"2026-03-04T13:08:10","slug":"her2-specific-synthetic-antigen-receptor-sar-t-cell-therapy-synergizes-with-radiotherapy-to-provide-improved-anti-tumor-efficacy-in-non-small-cell-lung-cancer-nsclcolga-demetra-biziotis","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/04\/her2-specific-synthetic-antigen-receptor-sar-t-cell-therapy-synergizes-with-radiotherapy-to-provide-improved-anti-tumor-efficacy-in-non-small-cell-lung-cancer-nsclcolga-demetra-biziotis\/","title":{"rendered":"HER2-Specific Synthetic Antigen Receptor (SAR) T Cell Therapy Synergizes with Radiotherapy to Provide Improved Anti-Tumor Efficacy in Non-Small Cell Lung Cancer (NSCLC)\u200bOlga-Demetra Biziotis   on 4 de March de 2026 at 11:00"},"content":{"rendered":"<div>\n<p><b>J Leukoc Biol<\/b>. 2026 Mar 3:qiag030. doi: 10.1093\/jleuko\/qiag030. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>In NSCLC, radiotherapy mediates cytotoxicity but also activates radioresistance drivers like HER2. We investigated radiotherapy combined with HER2-targeted T cell therapy in a NSCLC model. The anti-tumor efficacy of radiotherapy and engineered T cells expressing a DAP12-associated synthetic antigen receptor (SAR) targeting HER2 was evaluated in HER2-expressing A549 xenografts. HER2 modulation, transcriptional regulation and tumor T cell infiltration were assessed using immunoblotting, RT-qPCR, flow cytometry, RNA-seq and immunohistochemistry. High-dose HER2-SAR T cell infusion abolished A549 tumor growth but induced graft-versus-host disease. Low-dose T cell infusion was well-tolerated and provided partial tumor inhibition. Induction radiotherapy (7 days before T cell infusion) synergistically improved tumor control and survival. Radiotherapy transiently upregulated HER2 expression (4-24h), though administering HER2-SAR T cells within this window did not enhance anti-tumor efficacy. Radiation did not enhance T cell-mediated cytotoxicity in vitro. However, in tumors, radiotherapy increased intratumoral proliferation and accumulation of HER2-SAR T cells and enhanced the extrinsic apoptotic pathway, including induction of Fas transcript and protein levels and cleaved caspase-3 (CC3). RNA-seq of irradiated tumors revealed lasting transcriptional reprogramming with increased immune activation and decreased proliferation and oncogenic signaling. Induction radiotherapy enhances HER2-SAR T cell infiltration and provides synergistic tumor suppression, likely through additional activation of immune-mediated apoptosis. These findings support further assessment of HER2-SAR T cell therapy in HER2-expressing NSCLC.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41777114\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=8405628&amp;ff=20260304080800&amp;v=2.19.0.post6+133c1fe\">41777114<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jleuko\/qiag030\">10.1093\/jleuko\/qiag030<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Leukoc Biol. 2026 Mar 3:qiag030. doi: 10.1093\/jleuko\/qiag030. Online ahead of print. ABSTRACT In NSCLC, radiotherapy mediates cytotoxicity but also activates radioresistance drivers like HER2. We investigated radiotherapy combined with HER2-targeted T cell therapy in a NSCLC model. The anti-tumor efficacy of radiotherapy and engineered T cells expressing a DAP12-associated synthetic antigen receptor (SAR) targeting &#8230; <a title=\"HER2-Specific Synthetic Antigen Receptor (SAR) T Cell Therapy Synergizes with Radiotherapy to Provide Improved Anti-Tumor Efficacy in Non-Small Cell Lung Cancer (NSCLC)\u200bOlga-Demetra Biziotis   on 4 de March de 2026 at 11:00\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/03\/04\/her2-specific-synthetic-antigen-receptor-sar-t-cell-therapy-synergizes-with-radiotherapy-to-provide-improved-anti-tumor-efficacy-in-non-small-cell-lung-cancer-nsclcolga-demetra-biziotis\/\" aria-label=\"Read more about HER2-Specific Synthetic Antigen Receptor (SAR) T Cell Therapy Synergizes with Radiotherapy to Provide Improved Anti-Tumor Efficacy in Non-Small Cell Lung Cancer (NSCLC)\u200bOlga-Demetra Biziotis   on 4 de March de 2026 at 11:00\">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-57496","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\/57496","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=57496"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/57496\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=57496"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=57496"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=57496"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}