{"id":5739,"date":"2026-03-31T10:53:03","date_gmt":"2026-03-31T03:53:03","guid":{"rendered":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/?p=5739"},"modified":"2026-03-31T10:53:38","modified_gmt":"2026-03-31T03:53:38","slug":"dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer","status":"publish","type":"post","link":"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer\/","title":{"rendered":"Dual Targeting of FAP-Directed Nanoparticles and FR\u03b1-Specific CAR-T Cells Induces Additive Anti-Tumor Effects in Triple-Negative Breast Cancer"},"content":{"rendered":"<p>Tanva Thongkleang, Suyanee Thongchot, Kamonlatth Rodponthukwaji, Piriya Luangwattananun, Kwanruthai Tadpetch, Pa Thai Yenchitsomanus, Peti Thuwajit, <strong>Primana Punnakitikashem<\/strong>, Chanitra Thuwajit<\/p>\n<h2 class=\"title\">Abstract<\/h2>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<div class=\"title\">\n<p>Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited treatment options. It lacks hormone receptors and human epidermal growth factor receptor 2. The immunosuppressive tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), significantly hinders chimeric antigen receptor (CAR)-T cell therapy success. Novel strategies to overcome TME-mediated immunosuppression are urgently needed. We evaluated whether targeting CAFs with fibroblast activation protein alpha (FAP)-coated, 8-O-methylfusarubin-loaded nanoparticles called anti-FAP@OMF-NPs could enhance the anti-tumor efficacy of folate receptor alpha (FR\u03b1)-specific CAR-T cells against TNBC in a 3D cancer cells-CAFs co-culture heterospheriod (HS) model. FR\u03b1 and FAP expression in TNBC cells and primary breast CAFs were assessed using immunofluorescence and flow cytometry. Anti-FR\u03b1-CAR-T cells were generated via lentiviral transduction and characterised for activation markers. Cytotoxic activity of CAR-T cells, anti-FAP@OMF-NPs, and their combination was evaluated in 3D-HS comprising FR\u03b1-high TNBC cells and FAP-high CAFs. A fluorescent transfection assay measured cell viability. Cytokine bead arrays quantified IFN-\u03b3, granzyme A, and granzyme B levels to assess anti-tumor immune activation. PC-B-130CAFs and PC-B-132CAFs demonstrated high FAP expression compared with PC-B-004CAFs and normal human dermal fibroblast cells (HDFa). Anti-FR\u03b1-CAR-T cells selectively targeted FR\u03b1-positive TNBC cells whilst showing minimal cytotoxicity towards normal MCF-10A cells. Anti-FAP@OMF-NPs induced potent cytotoxic effects specifically in FAP-expressing CAFs. Combined treatment significantly enhanced the destruction of MDA-MB-231\/130CAF and MDA-MB-231\/132CAF HSs compared with monotherapies. This combination increased secretion of IFN-\u03b3, granzyme A, and granzyme B from anti-FR\u03b1-CAR-T cells. Targeting CAFs using anti-FAP@OMF-NPs enhances the cytotoxic efficacy of FR\u03b1-specific CAR-T cells in TNBC. This combinatorial approach offers a promising strategy to overcome TME-mediated immunosuppression. These findings support further development of dual-targeting approaches to improve therapeutic outcomes in TNBC.<\/p>\n<p><a href=\"https:\/\/murex.mahidol.ac.th\/en\/publications\/dual-targeting-of-fap-directed-nanoparticles-and-fr%CE%B1-specific-car\/\">https:\/\/murex.mahidol.ac.th\/en\/publications\/dual-targeting-of-fap-directed-nanoparticles-and-fr%CE%B1-specific-car\/<\/a><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Tanva Thongkleang, Suyanee Thongchot, Kamonlatth Rodponthukwaji, Piriya Luangwattananun, Kwanruthai Tadpetch, Pa Thai Yenchitsomanus, Peti Thuwajit, Primana Punnakitikashem, Chanitra Thuwajit Abstract Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited treatment options. It lacks hormone receptors and human epidermal growth factor receptor 2. The immunosuppressive tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), significantly hinders chimeric [&#8230;]\n","protected":false},"author":6,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18],"tags":[],"class_list":["post-5739","post","type-post","status-publish","format-standard","hentry","category-research-innovation-en"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Dual Targeting of FAP-Directed Nanoparticles and FR\u03b1-Specific CAR-T Cells Induces Additive Anti-Tumor Effects in Triple-Negative Breast Cancer - \u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Dual Targeting of FAP-Directed Nanoparticles and FR\u03b1-Specific CAR-T Cells Induces Additive Anti-Tumor Effects in Triple-Negative Breast Cancer - \u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"og:description\" content=\"Tanva Thongkleang, Suyanee Thongchot, Kamonlatth Rodponthukwaji, Piriya Luangwattananun, Kwanruthai Tadpetch, Pa Thai Yenchitsomanus, Peti Thuwajit, Primana Punnakitikashem, Chanitra Thuwajit Abstract Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited treatment options. It lacks hormone receptors and human epidermal growth factor receptor 2. The immunosuppressive tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), significantly hinders chimeric [...]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www2.si.mahidol.ac.th\/department\/biochemistry\/en\/dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer\/\" \/>\n<meta property=\"og:site_name\" content=\"\u0e20\u0e32\u0e04\u0e27\u0e34\u0e0a\u0e32\u0e0a\u0e35\u0e27\u0e40\u0e04\u0e21\u0e35 \u0e04\u0e13\u0e30\u0e41\u0e1e\u0e17\u0e22\u0e28\u0e32\u0e2a\u0e15\u0e23\u0e4c\u0e28\u0e34\u0e23\u0e34\u0e23\u0e32\u0e0a\u0e1e\u0e22\u0e32\u0e1a\u0e32\u0e25 \u0e21\u0e2b\u0e32\u0e27\u0e34\u0e17\u0e22\u0e32\u0e25\u0e31\u0e22\u0e21\u0e2b\u0e34\u0e14\u0e25\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/SIBBprogram\/\" \/>\n<meta property=\"article:published_time\" content=\"2026-03-31T03:53:03+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2026-03-31T03:53:38+00:00\" \/>\n<meta name=\"author\" content=\"Poorintra Sakuna\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Poorintra Sakuna\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www2.si.mahidol.ac.th\\\/department\\\/biochemistry\\\/en\\\/dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www2.si.mahidol.ac.th\\\/department\\\/biochemistry\\\/en\\\/dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer\\\/\"},\"author\":{\"name\":\"Poorintra Sakuna\",\"@id\":\"https:\\\/\\\/www2.si.mahidol.ac.th\\\/department\\\/biochemistry\\\/en\\\/#\\\/schema\\\/person\\\/75170c4a414d080cfd0b7428b2e0d11a\"},\"headline\":\"Dual Targeting of FAP-Directed Nanoparticles and FR\u03b1-Specific CAR-T Cells Induces Additive Anti-Tumor Effects in Triple-Negative Breast Cancer\",\"datePublished\":\"2026-03-31T03:53:03+00:00\",\"dateModified\":\"2026-03-31T03:53:38+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www2.si.mahidol.ac.th\\\/department\\\/biochemistry\\\/en\\\/dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer\\\/\"},\"wordCount\":336,\"publisher\":{\"@id\":\"https:\\\/\\\/www2.si.mahidol.ac.th\\\/department\\\/biochemistry\\\/en\\\/#organization\"},\"articleSection\":[\"Research Innovation\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www2.si.mahidol.ac.th\\\/department\\\/biochemistry\\\/en\\\/dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer\\\/\",\"url\":\"https:\\\/\\\/www2.si.mahidol.ac.th\\\/department\\\/biochemistry\\\/en\\\/dual-targeting-of-fap-directed-nanoparticles-and-fr%ce%b1-specific-car-t-cells-induces-additive-anti-tumor-effects-in-triple-negative-breast-cancer\\\/\",\"name\":\"Dual Targeting of FAP-Directed Nanoparticles and FR\u03b1-Specific CAR-T Cells Induces Additive Anti-Tumor Effects in Triple-Negative Breast Cancer - 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It lacks hormone receptors and human epidermal growth factor receptor 2. 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