{"id":65392,"date":"2026-05-25T19:28:30","date_gmt":"2026-05-25T17:28:30","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/05\/25\/preconditioning-determines-engraftment-and-therapeutic-efficacy-of-anti-cd19-car-t-cells-in-murine-lupus\/"},"modified":"2026-05-25T19:28:30","modified_gmt":"2026-05-25T17:28:30","slug":"preconditioning-determines-engraftment-and-therapeutic-efficacy-of-anti-cd19-car-t-cells-in-murine-lupus","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/05\/25\/preconditioning-determines-engraftment-and-therapeutic-efficacy-of-anti-cd19-car-t-cells-in-murine-lupus\/","title":{"rendered":"Preconditioning determines engraftment and therapeutic efficacy of anti-CD19 CAR-T cells in murine lupus"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 May 14;215(5):vkag112. doi: 10.1093\/jimmun\/vkag112.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Anti-CD19 chimeric antigen receptor (CAR) T cells have emerged as a promising therapeutic strategy for autoimmune diseases, including systemic lupus erythematosus. An unresolved question is how immunosuppressive preconditioning regimens influence CAR-T cell engraftment and therapeutic efficacy. In murine models, whole-body irradiation is required for optimal CAR-T cell engraftment. However, irradiation alone can ameliorate lupus disease, confounding attribution of CAR-T-specific effects. To delineate the contribution of CAR-T cells beyond irradiation, we investigated how conditioning intensity shapes immunologic and physiological outcomes in lupus-prone New Zealand Black\/New Zealand White (NZB\/W) F1 mice. We generated murine anti-CD19 CAR-T cells incorporating a CD28 costimulatory domain and compared their efficacy following low-, intermediate- and high-dose irradiation. High-dose irradiation induced disease improvement that limited mechanistic discrimination between irradiation- and CAR-T-mediated effects, whereas low-dose irradiation failed to support durable CAR-T cell engraftment. In contrast, an intermediate-dose irradiation regimen in 22-week-old mice achieved consistent CAR-T cell engraftment in lymphoid organs while minimizing irradiation-driven disease modulation. Under these conditions, CAR-T cell treatment induced significant depletion of B cells in blood and spleen, including na\u00efve B cells, marginal zone B cells, and plasma cells, accompanied by reduced anti-double-stranded DNA antibody levels and prevention of renal disease progression. Collectively, these findings demonstrate that intermediate-intensity conditioning enables mechanistic separation of CAR-T-mediated immune remodeling from irradiation effects in murine lupus and provide a preclinical framework that aligns with the pressing need for reduced-intensity lymphodepletion strategies in human CAR-T therapy for autoimmune diseases.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/42179345\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260525132829&amp;v=2.20.0\">42179345<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkag112\">10.1093\/jimmun\/vkag112<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 May 14;215(5):vkag112. doi: 10.1093\/jimmun\/vkag112. ABSTRACT Anti-CD19 chimeric antigen receptor (CAR) T cells have emerged as a promising therapeutic strategy for autoimmune diseases, including systemic lupus erythematosus. An unresolved question is how immunosuppressive preconditioning regimens influence CAR-T cell engraftment and therapeutic efficacy. In murine models, whole-body irradiation is required for optimal CAR-T cell &#8230; <a title=\"Preconditioning determines engraftment and therapeutic efficacy of anti-CD19 CAR-T cells in murine lupus\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/05\/25\/preconditioning-determines-engraftment-and-therapeutic-efficacy-of-anti-cd19-car-t-cells-in-murine-lupus\/\" aria-label=\"Read more about Preconditioning determines engraftment and therapeutic efficacy of anti-CD19 CAR-T cells in murine lupus\">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":[42,71],"tags":[],"class_list":["post-65392","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/65392","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=65392"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/65392\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=65392"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=65392"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=65392"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}