{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:04:06Z","timestamp":1792019046588,"version":"4.4.0"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T00:00:00Z","timestamp":1721001600000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NEXTGENERATION EU","award":["project MNESYS (PE0000006)"],"award-info":[{"award-number":["project MNESYS (PE0000006)"]}]},{"name":"Italian Health ministry","award":["\u201dLife Science Hub -  Advanced Therapies (LSH - AT) Financed by Health Ministry as a part of the The National Plan for Complementary Investments to the NRRP - E.3 Innovative health eco system for APC fees"],"award-info":[{"award-number":["\u201dLife Science Hub -  Advanced Therapies (LSH - AT) Financed by Health Ministry as a part of the The National Plan for Complementary Investments to the NRRP - E.3 Innovative health eco system for APC fees"]}]},{"name":"Italian Health ministry","award":["immunomonitoring"],"award-info":[{"award-number":["immunomonitoring"]}]},{"name":"Italian Ministry of University and reaserch","award":["HEAL ITALIA- Health Extended ALliance for Innovative Therapies,Advanced Lab-research,"],"award-info":[{"award-number":["HEAL ITALIA- Health Extended ALliance for Innovative Therapies,Advanced Lab-research,"]}]},{"name":"Italian Ministry of University and reaserch","award":["Integrated Approaches of Precision Medicine -  funding  from MUR under  the National Recovery"],"award-info":[{"award-number":["Integrated Approaches of Precision Medicine -  funding  from MUR under  the National Recovery"]}]},{"name":"Italian Ministry of University and reaserch","award":["Resilience Plan (NRRP),Mission 4 Component 2 Investment 1.3 funded f"],"award-info":[{"award-number":["Resilience Plan (NRRP),Mission 4 Component 2 Investment 1.3 funded f"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Predicting immune effector cell\u2013associated neurotoxicity syndrome (ICANS) in patients infused with CAR T cells is still a conundrum. This complication, thought to be consequent to CAR T cell activation, arises a few days after infusion, when circulating CAR T cells are scarce and specific CAR T cell\u2013derived biomarkers are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      CAR\n                      <jats:sup>+<\/jats:sup>\n                      extracellular vesicle (CAR\n                      <jats:sup>+<\/jats:sup>\n                      EV) release was assessed in human CD19.CAR T cells cocultured with CD19\n                      <jats:sup>+<\/jats:sup>\n                      target cells. A prospective cohort of 100 patients with B cell lymphoma infused with approved CD19.CAR T cell products was assessed for plasma CAR\n                      <jats:sup>+<\/jats:sup>\n                      EVs as biomarkers of in vivo CD19.CAR T cell activation. Human induced pluripotent stem cell\u2013derived (iPSC-derived) neural cells were used as a model for CAR\n                      <jats:sup>+<\/jats:sup>\n                      EV-induced neurotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In vitro release of CAR\n                      <jats:sup>+<\/jats:sup>\n                      EVs occurs within 1 hour after target engagement. Plasma CAR\n                      <jats:sup>+<\/jats:sup>\n                      EVs are detectable 1 hour after infusion. A concentration greater than 132.8 CAR\n                      <jats:sup>+<\/jats:sup>\n                      EVs\/\u03bcL at hour +1 or greater than 224.5 CAR\n                      <jats:sup>+<\/jats:sup>\n                      EVs\/\u03bcL at day +1 predicted ICANS in advance of 4 days, with a sensitivity and a specificity outperforming other ICANS predictors. ENO2\n                      <jats:sup>+<\/jats:sup>\n                      nanoparticles were released by iPSC-derived neural cells upon CAR\n                      <jats:sup>+<\/jats:sup>\n                      EV exposure and were increased in plasma of patients with ICANS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Plasma CAR\n                      <jats:sup>+<\/jats:sup>\n                      EVs are an immediate signal of CD19.CAR T cell activation, are suitable predictors of neurotoxicity, and may be involved in ICANS pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>NCT04892433, NCT05807789.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Life Science Hub\u2013Advanced Therapies (financed by Health Ministry as part of the National Plan for Complementary Investments to the National Recovery and Resilience Plan [NRRP]: E.3 Innovative health ecosystem for APC fees and immunomonitoring).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci173096","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T07:34:21Z","timestamp":1717659261000},"source":"Crossref","is-referenced-by-count":35,"title":["CAR+ extracellular vesicles predict ICANS in patients with B cell lymphomas treated with CD19-directed CAR T cells"],"prefix":"10.1172","volume":"134","author":[{"given":"Gianluca","family":"Storci","sequence":"first","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De 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