{"id":33925,"date":"2025-06-02T18:48:49","date_gmt":"2025-06-02T16:48:49","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/06\/02\/secretion-of-a-vegf-blocking-scfv-enhances-car-t-cell-potency\/"},"modified":"2025-06-02T18:48:49","modified_gmt":"2025-06-02T16:48:49","slug":"secretion-of-a-vegf-blocking-scfv-enhances-car-t-cell-potency","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/06\/02\/secretion-of-a-vegf-blocking-scfv-enhances-car-t-cell-potency\/","title":{"rendered":"Secretion of a VEGF-blocking scFv enhances CAR T-cell potency"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Jun 2. doi: 10.1158\/2326-6066.CIR-24-0876. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>CAR T-cell therapy is an effective treatment strategy in B-cell malignancies, however, its efficacy in solid tumors remains limited. VEGF-targeted drugs are used as antitumor agents to target abnormal tumor vasculature, however, toxicities associated with systemic VEGF blockade limit their maximal therapeutic benefit. Increasing evidence suggests a role for VEGF in the immunosuppressive tumor microenvironment (TME), including through direct induction of T cell-effector dysfunction. Herein, we show that CAR T cells from patients treated with FDA-approved CAR T-cell products express members of the VEGF signaling pathway and this expression is correlated with patient non-response. To overcome putative VEGF-induced CAR T-cell dysfunction and deliver local VEGF blockade, we generated CAR T cells that secrete a VEGF-targeting scFv to block T-cell and tumor-derived VEGF within the TME. These CAR T cells potently inhibited VEGF signaling and angiogenesis in vitro, and exhibited enhanced activation, cytotoxicity, proliferation, and effector function across different antigen and solid tumor contexts. VEGF scFv-secreting CAR T cells showed improved tumor control in immunocompromised murine metastatic and orthotopic models of ovarian and lung cancer. These findings suggest that CAR T cell-secreted VEGF blockade augments CAR T-cell performance, inhibits VEGF without systemic toxicity, and warrants further development.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40455064\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250602124848&amp;v=2.18.0.post9+e462414\">40455064<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0876\">10.1158\/2326-6066.CIR-24-0876<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Jun 2. doi: 10.1158\/2326-6066.CIR-24-0876. Online ahead of print. ABSTRACT CAR T-cell therapy is an effective treatment strategy in B-cell malignancies, however, its efficacy in solid tumors remains limited. VEGF-targeted drugs are used as antitumor agents to target abnormal tumor vasculature, however, toxicities associated with systemic VEGF blockade limit their maximal therapeutic &#8230; <a title=\"Secretion of a VEGF-blocking scFv enhances CAR T-cell potency\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/06\/02\/secretion-of-a-vegf-blocking-scfv-enhances-car-t-cell-potency\/\" aria-label=\"Read more about Secretion of a VEGF-blocking scFv enhances CAR T-cell potency\">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-33925","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\/33925","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=33925"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/33925\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=33925"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=33925"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=33925"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}