{"id":16860,"date":"2024-09-29T09:29:35","date_gmt":"2024-09-29T07:29:35","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/ptprz1-targeting-rna-car-t-cells-exert-antigen-specific-and-bystander-antitumor-activity-in-glioblastoma\/"},"modified":"2024-09-29T09:29:35","modified_gmt":"2024-09-29T07:29:35","slug":"ptprz1-targeting-rna-car-t-cells-exert-antigen-specific-and-bystander-antitumor-activity-in-glioblastoma","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/ptprz1-targeting-rna-car-t-cells-exert-antigen-specific-and-bystander-antitumor-activity-in-glioblastoma\/","title":{"rendered":"PTPRZ1-targeting RNA CAR T cells exert antigen-specific and bystander antitumor activity in glioblastoma"},"content":{"rendered":"<div>\n<p>Cancer Immunol Res. 2024 Sep 13. doi: 10.1158\/2326-6066.CIR-23-1094. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>The great success of chimeric antigen receptor (CAR) T-cell therapy in the treatment of patients with B-cell malignancies has prompted its translation to solid tumors. In the case of glioblastoma (GBM), clinical trials have shown modest efficacy, but efforts to develop more effective anti-GBM CAR T cells are ongoing. In this study, we selected PTPRZ1 as a target for GBM treatment. We isolated six anti-human PTPRZ1 scFv from a human phage display library and produced 2nd generation CAR T cells in an RNA format. Patient-derived GBM PTPRZ1-knock-in cell lines were used to select the CAR construct that showed high cytotoxicity while consistently displaying high CAR expression (471_28z). CAR T cells incorporating 471_28z were able to release IFN-\u03b3, IL-2, TNF-\u03b1, Granzyme B, IL-17A, IL-6, and soluble FasL, and displayed low tonic signaling. Additionally, they maintained an effector memory phenotype after in vitro killing. In addition, 471_28z CAR T cells displayed strong bystander killing against PTPRZ1-negative cell lines after pre-activation by PTPRZ1-positive tumor cells but did not kill antigen-negative non-tumor cells. In an orthotopic xenograft tumor model using NSG mice, a single dose of anti-PTPRZ1 CAR T cells significantly delayed tumor growth. Taken together, these results validate PTPRZ1 as a GBM target and prompt the clinical translation of anti-PTPRZ1 CAR T cells.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39269445\/?utm_source=Chrome&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20240929032735&amp;v=2.18.0.post9+e462414\">39269445<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-23-1094\">10.1158\/2326-6066.CIR-23-1094<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2024 Sep 13. doi: 10.1158\/2326-6066.CIR-23-1094. Online ahead of print. ABSTRACT The great success of chimeric antigen receptor (CAR) T-cell therapy in the treatment of patients with B-cell malignancies has prompted its translation to solid tumors. In the case of glioblastoma (GBM), clinical trials have shown modest efficacy, but efforts to develop more &#8230; <a title=\"PTPRZ1-targeting RNA CAR T cells exert antigen-specific and bystander antitumor activity in glioblastoma\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/ptprz1-targeting-rna-car-t-cells-exert-antigen-specific-and-bystander-antitumor-activity-in-glioblastoma\/\" aria-label=\"Read more about PTPRZ1-targeting RNA CAR T cells exert antigen-specific and bystander antitumor activity in glioblastoma\">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-16860","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\/16860","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=16860"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16860\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=16860"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=16860"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=16860"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}