{"id":16857,"date":"2024-09-29T09:29:35","date_gmt":"2024-09-29T07:29:35","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/peripheral-blood-derived-pd-1-cd28-cd19-car-modified-pd-1-t-cell-therapy-in-patients-with-solid-tumors-2\/"},"modified":"2024-09-29T09:29:35","modified_gmt":"2024-09-29T07:29:35","slug":"peripheral-blood-derived-pd-1-cd28-cd19-car-modified-pd-1-t-cell-therapy-in-patients-with-solid-tumors-2","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/peripheral-blood-derived-pd-1-cd28-cd19-car-modified-pd-1-t-cell-therapy-in-patients-with-solid-tumors-2\/","title":{"rendered":"Peripheral blood-derived PD-1\/CD28-CD19-CAR-modified PD-1+ T-cell therapy in patients with solid tumors"},"content":{"rendered":"<div>\n<p>Cancer Immunol Res. 2024 Sep 16. doi: 10.1158\/2326-6066.CIR-24-0037. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>T cells expressing PD-1 in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1- T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T cell activation-related pathways compared with PD-1- T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity towards autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1\/CD28 fusion receptor combined with a CD19 chimeric antigen receptor (CAR) into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1\/CD28-CD19-CAR PD-1+ T cells. None of these patients experienced severe side effects and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for cancer patients.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39283669\/?utm_source=Chrome&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20240929032735&amp;v=2.18.0.post9+e462414\">39283669<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-24-0037\">10.1158\/2326-6066.CIR-24-0037<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2024 Sep 16. doi: 10.1158\/2326-6066.CIR-24-0037. Online ahead of print. ABSTRACT T cells expressing PD-1 in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction &#8230; <a title=\"Peripheral blood-derived PD-1\/CD28-CD19-CAR-modified PD-1+ T-cell therapy in patients with solid tumors\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/09\/29\/peripheral-blood-derived-pd-1-cd28-cd19-car-modified-pd-1-t-cell-therapy-in-patients-with-solid-tumors-2\/\" aria-label=\"Read more about Peripheral blood-derived PD-1\/CD28-CD19-CAR-modified PD-1+ T-cell therapy in patients with solid 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-16857","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\/16857","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=16857"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/16857\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=16857"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=16857"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=16857"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}