{"id":42359,"date":"2025-09-08T18:49:18","date_gmt":"2025-09-08T16:49:18","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/08\/systematic-engineering-of-trop2-targeted-car-t-cell-therapy-overcomes-resistance-pathways-in-solid-tumors\/"},"modified":"2025-09-08T18:49:18","modified_gmt":"2025-09-08T16:49:18","slug":"systematic-engineering-of-trop2-targeted-car-t-cell-therapy-overcomes-resistance-pathways-in-solid-tumors","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/08\/systematic-engineering-of-trop2-targeted-car-t-cell-therapy-overcomes-resistance-pathways-in-solid-tumors\/","title":{"rendered":"Systematic engineering of TROP2-targeted CAR T-cell therapy overcomes resistance pathways in solid tumors"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Sep 8. doi: 10.1158\/2326-6066.CIR-25-0527. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Antibody-based therapies have revolutionized cancer treatment but have several limitations. These include: down-regulation of the target antigen; mutation of the target epitope; or in the case of antibody drug conjugates (ADCs), resistance to the chemotherapy warhead. Since TROP2-targeted therapy with ADCs yields responses in TROP2+ solid tumors but lacks the durability observed with other immunotherapy-based approaches, we developed novel TROP2-targeting chimeric antigen receptor (CAR) T cells as an alternative. We observe high potency of TROP2 directed CAR T against multiple solid tumor models. We demonstrate that CAR T cell therapy can preserve high potency in models of ADC resistance and can be further engineered to prevent cell therapy resistance; leveraging fully-human single domain (VH-only) binder discovery to rationally engineer dual epitope-binding based (biparatopic) CARs. This work highlights the potency of CAR T cell therapies and how rational engineering leveraging dual-VH targeting domains can overcome resistance pathways to current therapies. In future work, the CAR engineering approaches presented here can serve as a platform to be partnered with other strategies to address the suppressive tumor microenvironment. This work highlights the potency of CAR T cell therapies and how rational engineering leveraging dual-VH targeting domains can overcome resistance pathways to current therapies.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40920095\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250908124914&amp;v=2.18.0.post9+e462414\">40920095<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0527\">10.1158\/2326-6066.CIR-25-0527<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Sep 8. doi: 10.1158\/2326-6066.CIR-25-0527. Online ahead of print. ABSTRACT Antibody-based therapies have revolutionized cancer treatment but have several limitations. These include: down-regulation of the target antigen; mutation of the target epitope; or in the case of antibody drug conjugates (ADCs), resistance to the chemotherapy warhead. Since TROP2-targeted therapy with ADCs yields &#8230; <a title=\"Systematic engineering of TROP2-targeted CAR T-cell therapy overcomes resistance pathways in solid tumors\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/09\/08\/systematic-engineering-of-trop2-targeted-car-t-cell-therapy-overcomes-resistance-pathways-in-solid-tumors\/\" aria-label=\"Read more about Systematic engineering of TROP2-targeted CAR T-cell therapy overcomes resistance pathways in solid tumors\">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-42359","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\/42359","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=42359"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/42359\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=42359"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=42359"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=42359"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}