{"id":69235,"date":"2026-07-03T19:17:07","date_gmt":"2026-07-03T17:17:07","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/07\/03\/car-t-cells-targeting-o-glycosylated-fibronectin-exhibit-potent-cytolytic-activity-and-combine-with-tumoral-toll-like-receptor-agonism-to-overcome-tumor-resistance\/"},"modified":"2026-07-03T19:17:07","modified_gmt":"2026-07-03T17:17:07","slug":"car-t-cells-targeting-o-glycosylated-fibronectin-exhibit-potent-cytolytic-activity-and-combine-with-tumoral-toll-like-receptor-agonism-to-overcome-tumor-resistance","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/07\/03\/car-t-cells-targeting-o-glycosylated-fibronectin-exhibit-potent-cytolytic-activity-and-combine-with-tumoral-toll-like-receptor-agonism-to-overcome-tumor-resistance\/","title":{"rendered":"CAR T Cells Targeting O-Glycosylated Fibronectin Exhibit Potent Cytolytic Activity and Combine with Tumoral Toll-Like Receptor Agonism to Overcome Tumor Resistance"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Jul 3. doi: 10.1158\/2326-6066.CIR-26-0009. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Tumors remodel extracellular matrix (ECM) and glycosylation, yielding epitopes with restricted or limited detectability in normal adult tissues. Here, we evaluated the O-glycosylated IIICS domain of fibronectin (Tn-FN) as a chimeric antigen receptor (CAR) T cell target. FDC6-BB\u03b6 CAR T cells recognizing Tn-FN were benchmarked against EDB-FN-targeted L19-BB\u03b6 and Tn-MUC1-targeted 5E5-BB\u03b6. FDC6-BB\u03b6 mediated robust, antigen-dependent activation and cytotoxicity, outperforming L19-BB\u03b6 and matching 5E5-BB\u03b6 in vitro and in NSG xenografts of prostate cancer. FDC6-BB\u03b6 and 5E5-BB\u03b6 CAR T cells achieved durable tumor control with increased intratumoral CD3\u207a infiltration and reduced tumor-collagen overlap. Cytotoxicity required intact tumor interferon-\u03b3 (IFN\u03b3) receptor 1; L19-BB\u03b6 further depended on Fas, whereas FDC6-BB\u03b6 and 5E5-BB\u03b6 were less Fas-dependent. Tumoral toll-like receptor (TLR) 2\/6 or TLR4 agonism restored FDC6-BB\u03b6 killing of IFN\u03b3R1-deficient targets and induced broad inflammatory and stress-response programs. Pharmacologic perturbation implicated caspase-dependent mechanisms and a contribution from inflammasome-linked signaling, whereas ferroptosis blockade did not abrogate restored killing. These findings establish Tn-FN as a glycoform-restricted, ECM-derived CAR target and show that innate agonists can reprogram tumor state to overcome resistance from impaired IFN\u03b3 signaling.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42397032\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260703131706&amp;v=2.20.0\">42397032<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-26-0009\">10.1158\/2326-6066.CIR-26-0009<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Jul 3. doi: 10.1158\/2326-6066.CIR-26-0009. Online ahead of print. ABSTRACT Tumors remodel extracellular matrix (ECM) and glycosylation, yielding epitopes with restricted or limited detectability in normal adult tissues. Here, we evaluated the O-glycosylated IIICS domain of fibronectin (Tn-FN) as a chimeric antigen receptor (CAR) T cell target. FDC6-BB\u03b6 CAR T cells recognizing &#8230; <a title=\"CAR T Cells Targeting O-Glycosylated Fibronectin Exhibit Potent Cytolytic Activity and Combine with Tumoral Toll-Like Receptor Agonism to Overcome Tumor Resistance\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/07\/03\/car-t-cells-targeting-o-glycosylated-fibronectin-exhibit-potent-cytolytic-activity-and-combine-with-tumoral-toll-like-receptor-agonism-to-overcome-tumor-resistance\/\" aria-label=\"Read more about CAR T Cells Targeting O-Glycosylated Fibronectin Exhibit Potent Cytolytic Activity and Combine with Tumoral Toll-Like Receptor Agonism to Overcome Tumor Resistance\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-69235","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\/69235","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=69235"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/69235\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=69235"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=69235"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=69235"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}