{"id":41929,"date":"2025-09-02T02:51:17","date_gmt":"2025-09-02T00:51:17","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/09\/02\/tunneling-cars-increasing-car-t-cell-tumor-infiltration-through-the-overexpression-of-mmp-7-and-osteopontin-b\/"},"modified":"2025-09-02T02:51:17","modified_gmt":"2025-09-02T00:51:17","slug":"tunneling-cars-increasing-car-t-cell-tumor-infiltration-through-the-overexpression-of-mmp-7-and-osteopontin-b","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/09\/02\/tunneling-cars-increasing-car-t-cell-tumor-infiltration-through-the-overexpression-of-mmp-7-and-osteopontin-b\/","title":{"rendered":"Tunneling CARs: Increasing CAR T-cell tumor infiltration through the overexpression of MMP-7 and Osteopontin-b"},"content":{"rendered":"<div>\n<p><b>Cancer Immunol Res<\/b>. 2025 Sep 1. doi: 10.1158\/2326-6066.CIR-25-0149. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy against hematologic malignancies but has struggled to achieve comparable success in solid tumors. A key obstacle in solid tumors is the extracellular matrix (ECM), which impedes CAR T-cell infiltration. In clinical trials, neuroblastoma (NB) has shown responsiveness to GD2-directed CAR T-cell therapy, however, the failure of GD2.CAR T cells to effectively clear bulky disease &#8211; characterized by dense ECM &#8211; highlights the critical challenge of infiltration. In this study, we demonstrate that GD2.CAR T cells exhibit a unique infiltration-restriction compared to other CAR T cells and endogenous T cells. A separate analysis of clinical datasets identified MMP7 and SPP1 (which encodes osteopontin; OPN) as candidate genes to improve the infiltration of GD2.CAR T cells as these were upregulated in tumor-infiltrating leukocytes. MMP-7 and OPN overexpression enhanced CAR T-cell extravasation and interstitial movement in ECM-dense environments in vitro. Overexpression of either OPN or MMP-7 significantly improved tumor infiltration in a xenograft model of NB. This resulted in improved tumor control and a survival extension in OPN-GD2.CAR T-cell treated mice compared to unmodified GD2.CAR T cells. OPN overexpression did not increase off-target infiltration into healthy tissues or promote tumor metastasis, highlighting its potential for safe therapeutic application. Our study provides a framework for further exploration of gene modifications to improve CAR T-cell infiltration in solid tumors and identifies OPN as a candidate to explore in this regard.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40889278\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20250901205114&amp;v=2.18.0.post9+e462414\">40889278<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-25-0149\">10.1158\/2326-6066.CIR-25-0149<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2025 Sep 1. doi: 10.1158\/2326-6066.CIR-25-0149. Online ahead of print. ABSTRACT Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy against hematologic malignancies but has struggled to achieve comparable success in solid tumors. A key obstacle in solid tumors is the extracellular matrix (ECM), which impedes CAR T-cell infiltration. In clinical trials, &#8230; <a title=\"Tunneling CARs: Increasing CAR T-cell tumor infiltration through the overexpression of MMP-7 and Osteopontin-b\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/09\/02\/tunneling-cars-increasing-car-t-cell-tumor-infiltration-through-the-overexpression-of-mmp-7-and-osteopontin-b\/\" aria-label=\"Read more about Tunneling CARs: Increasing CAR T-cell tumor infiltration through the overexpression of MMP-7 and Osteopontin-b\">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-41929","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\/41929","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=41929"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/41929\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=41929"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=41929"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=41929"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}