{"id":56288,"date":"2026-02-13T19:08:08","date_gmt":"2026-02-13T18:08:08","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/02\/13\/targeted-lipid-nanoparticle-delivery-of-fap-car-mrna-enables-potent-in-vivo-t-cell-engineering-against-pancreatic-tumors\/"},"modified":"2026-02-13T19:08:08","modified_gmt":"2026-02-13T18:08:08","slug":"targeted-lipid-nanoparticle-delivery-of-fap-car-mrna-enables-potent-in-vivo-t-cell-engineering-against-pancreatic-tumors","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/02\/13\/targeted-lipid-nanoparticle-delivery-of-fap-car-mrna-enables-potent-in-vivo-t-cell-engineering-against-pancreatic-tumors\/","title":{"rendered":"Targeted Lipid Nanoparticle Delivery of FAP-CAR mRNA Enables Potent In Vivo T-Cell Engineering Against Pancreatic Tumors"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2026 Feb 13. doi: 10.1158\/2326-6066.CIR-25-0663. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Fibroblast activation protein (FAP), which is highly expressed on cancer-associated fibroblasts (CAFs), is a promising therapeutic target to achieve normalization of the tumor microenvironment. We previously established an ex vivo retroviral-transduced FAP-specific chimeric antigen receptor (FAP-CAR) T-cell approach to deplete FAP+ CAFs that resulted in delayed tumor growth associated with disruption of desmoplastic matrix, enhanced immune-cell infiltration, and reversed immune exclusion and immunosuppression. Herein, we describe an in vivo strategy for generating FAP-CAR T cells using anti-CD5-conjugated targeted lipid nanoparticles (tLNPs) encapsulating FAP-CAR mRNA and assessed the efficacy of this approach compared to adoptive transfer of retrovirus-transduced CAR T cells in a preclinical model of pancreatic ductal adenocarcinoma. With transient CAR expression in &gt;45% of splenic, &gt;69% of circulating, and &gt;35% of tumor-infiltrating T cells, the abundance of peripheral and intratumoral FAP-CAR+ T cells detected following a single intravenous dose of FAP-CAR mRNA tLNPs was greater than that detected following administration of 1&#215;107 ex vivo retrovirally-transduced FAP-CAR T cells. Furthermore, in vivo mRNA CAR T-cell engineering resulted in as good or greater inhibition of tumor growth as compared to adoptive transfer of ex vivo retroviral-engineered T cells. Given that in vivo generation of CAR T cells resulted in transient CAR expression and circumvented the need for autologous T-cell isolation, viral vectors, and lymphodepletion, this platform represents a potentially safer, more accessible, and cost-effective method for targeting stromal cells to normalize the tumor microenvironment in desmoplastic tumors and has potential implications for tumor antigen-targeted CAR T cells.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41686204\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20260213130801&amp;v=2.18.0.post22+67771e2\">41686204<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0663\">10.1158\/2326-6066.CIR-25-0663<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2026 Feb 13. doi: 10.1158\/2326-6066.CIR-25-0663. Online ahead of print. ABSTRACT Fibroblast activation protein (FAP), which is highly expressed on cancer-associated fibroblasts (CAFs), is a promising therapeutic target to achieve normalization of the tumor microenvironment. We previously established an ex vivo retroviral-transduced FAP-specific chimeric antigen receptor (FAP-CAR) T-cell approach to deplete FAP+ CAFs &#8230; <a title=\"Targeted Lipid Nanoparticle Delivery of FAP-CAR mRNA Enables Potent In Vivo T-Cell Engineering Against Pancreatic Tumors\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/02\/13\/targeted-lipid-nanoparticle-delivery-of-fap-car-mrna-enables-potent-in-vivo-t-cell-engineering-against-pancreatic-tumors\/\" aria-label=\"Read more about Targeted Lipid Nanoparticle Delivery of FAP-CAR mRNA Enables Potent In Vivo T-Cell Engineering Against Pancreatic 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-56288","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\/56288","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=56288"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/56288\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=56288"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=56288"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=56288"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}