{"id":33687,"date":"2025-05-29T19:47:09","date_gmt":"2025-05-29T17:47:09","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/05\/29\/nanobody-directed-cea-targeting-car-t-cells-eliminate-gastrointestinal-cancer-xenografts\/"},"modified":"2025-05-29T19:47:09","modified_gmt":"2025-05-29T17:47:09","slug":"nanobody-directed-cea-targeting-car-t-cells-eliminate-gastrointestinal-cancer-xenografts","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/05\/29\/nanobody-directed-cea-targeting-car-t-cells-eliminate-gastrointestinal-cancer-xenografts\/","title":{"rendered":"Nanobody-Directed CEA-targeting CAR T Cells Eliminate Gastrointestinal Cancer Xenografts"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 May 29. doi: 10.1158\/2326-6066.CIR-24-0137. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Gastrointestinal cancers (GICs), including gastric cancers (GCs) and colorectal cancers (CRCs), are among the leading causes of cancer-related deaths worldwide. Metastatic GCs and CRCs often develop resistance or fail to respond to current therapies. Adoptive T-cell immunotherapy, especially with T cells expressing chimeric antigen receptors (CAR) targeting CD19, has revolutionized leukemia treatment. However, the development of CAR T-cell therapy for GICs is still in progress. Here, we used a Sequentially Tumor-selected Antibody and Antigen Retrieval (STAR) system to isolate a nanobody that directs CAR T cells to attack GI tumor cells in preclinical mouse models. The nanobody VHHB30 specifically binds to the N-terminal (non-glycosylated) domain of carcinoembryonic antigen (CEA). The resulting VHHB30-CAR T cells (CEACARTs) exhibited cytotoxicity against both CRC and GC cell lines in vitro in a CEA-dependent manner. Moreover, third-generation CEACARTs showed enhanced antitumor activity compared to second-generation CEACARTs. Further, in vivo studies demonstrated that the CEACARTs eradicated various colorectal and gastric tumor xenografts in preclinical mouse models, highlighting a promising approach for CAR T-cell therapy development in GICs through unbiased in vivo selection of potent VHH binders.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40439687\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250529134708&amp;v=2.18.0.post9+e462414\">40439687<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0137\">10.1158\/2326-6066.CIR-24-0137<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 May 29. doi: 10.1158\/2326-6066.CIR-24-0137. Online ahead of print. ABSTRACT Gastrointestinal cancers (GICs), including gastric cancers (GCs) and colorectal cancers (CRCs), are among the leading causes of cancer-related deaths worldwide. Metastatic GCs and CRCs often develop resistance or fail to respond to current therapies. Adoptive T-cell immunotherapy, especially with T cells expressing &#8230; <a title=\"Nanobody-Directed CEA-targeting CAR T Cells Eliminate Gastrointestinal Cancer Xenografts\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/05\/29\/nanobody-directed-cea-targeting-car-t-cells-eliminate-gastrointestinal-cancer-xenografts\/\" aria-label=\"Read more about Nanobody-Directed CEA-targeting CAR T Cells Eliminate Gastrointestinal Cancer Xenografts\">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-33687","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\/33687","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=33687"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/33687\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=33687"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=33687"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=33687"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}