{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:53:23Z","timestamp":1784912003270,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Adoptive therapy with CD19 chimeric antigen receptor (CAR) T cells is effective against B-cell malignancies; however, T-cell activation rapidly declines, increasing the risk of early leukemia relapses. To augment CD19 CAR T-cell functionality, we interfered with the physiological control of T-cell activation by a CAR that prevents the T cell\u2019s inherent CD30\u2013CD30L interaction. Redirected by the bispecific CD30\/CD19 CAR, T cells were superior to canonical CD19 CAR T cells in eliminating CD30\n                    <jats:sup>-<\/jats:sup>\n                    CD19\n                    <jats:sup>+<\/jats:sup>\n                    cells. Also, CD19\n                    <jats:sup>+<\/jats:sup>\n                    B acute leukemia cells from patients were more efficiently eliminated by the CD30\/CD19 CAR T cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    than by CD19 CAR T cells. For simultaneous CD30 blocking and CD19 targeting, the scFv order CD30\/CD19 in the CAR was superior to CD19\/CD30 in forming an optimal synaptic gap. The extended T-cell functionality was not due to binding of any two targets since the bispecific CD20\/CD19 CAR was less efficient. Preventing the CD30\u2013CD30L interaction results in reduced TRAF2 levels, increased I\u03baB\u03b1, late partial feedback Ser529-p65 phosphorylation, a moderate pSTAT3 elevation, enhanced granzyme B\/IFN-\u03b3 production, and a dampened Th2 polarization, shifting CD8+ CAR T cells from an immunosuppressive to a more cytotoxic phenotype. Our data demonstrate a strategy in augmenting the efficacy of CD19 CAR T cells against B-cell malignancies by concomitant blocking the T cell\u2019s own CD30\u2013CD30L interaction.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1725641","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:29:26Z","timestamp":1777526966000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Blocking CD30 on CD19 CAR T cells augments their functional capacities against B-cell leukemia\/lymphoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Tim","family":"Schlierkamp-Voosen","sequence":"first","affiliation":[{"name":"Div. Genetic Immunotherapy, Leibniz Institute for Immunotherapy","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Barden","sequence":"additional","affiliation":[{"name":"Div. Genetic Immunotherapy, Leibniz Institute for Immunotherapy","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Janning","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital Regensburg","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcell","family":"Kaljanac","sequence":"additional","affiliation":[{"name":"Div. Genetic Immunotherapy, Leibniz Institute for Immunotherapy","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis Christoph","family":"Harrer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital Regensburg","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Dreger","sequence":"additional","affiliation":[{"name":"Div. Genetic Immunotherapy, Leibniz Institute for Immunotherapy","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Hammon","sequence":"additional","affiliation":[{"name":"Div. Genetic Immunotherapy, Leibniz Institute for Immunotherapy","place":["Regensburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Ertelt","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery, Faculty of Medicine, Leipzig University","place":["Leipzig, Germany"]},{"name":"Center for Scalable Data Analytics and Artificial Intelligence ScaDS. 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