{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:26:57Z","timestamp":1786688817430,"version":"build-2736575974"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of hematologic malignancies but remains largely ineffective against solid tumors, where stromal barriers and an immunosuppressive microenvironment restrict T-cell infiltration and function. Cell-free vesicular derivatives of therapeutic lymphocytes may help overcome these limitations while preserving antigen specificity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Artificial vesicles were generated from CAR-T cells (CAR-AVs) by brief ultrasonication followed by differential centrifugation. Their physicochemical and functional properties were evaluated in vitro using scanning electron microscopy, flow cytometry with DiO labeling and recombinant CD19\u2013PE, real-time impedance analysis, and qRT-PCR of apoptosis-associated genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Scanning electron microscopy revealed nanoscale, membrane-enclosed vesicles with mean \u00b1 SD diameters of 132 \u00b1 76 nm for CAR-AVs and 149 \u00b1 63 nm for T cell-derived vesicles (T-AVs). Flow cytometry detected CAR expression on 52.7 \u00b1 20.5% of CAR-AVs, compared with 8.3 \u00b1 6.1% background staining in T-AVs and 64.2 \u00b1 14.4% CD19\u2013PE-positive parental CAR-T cells. At a protein-normalized dose of 15 \u00b5g mL\u20131, CAR-AVs selectively suppressed the proliferation of CD19-expressing tumor cells, reducing the cell index by approximately 26\u201327% in PC3M(CD19+) cultures and 68% in A431(CD19+) cultures, with minimal effects on antigen-negative counterparts. T-AVs induced only modest, antigen-independent suppression. In antigen-positive models, CAR-AV treatment upregulated\n                      <jats:italic>MDM2, CDKN1A\/p21, BBC3\/PUMA<\/jats:italic>\n                      , and\n                      <jats:italic>BAX<\/jats:italic>\n                      , consistent with activation of stress- and apoptosis-associated signaling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Ultrasonication-derived CAR-AVs preserve detectable CAR display and retain antigen-associated antitumor activity in solid-tumor models. These findings support CAR-AVs as a promising and potentially scalable cell-free complement to CAR-T therapy, while highlighting the need for particle-resolved quantification, dose-response studies, and\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1895812","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:32:03Z","timestamp":1786685523000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasonication-derived CAR-T vesicles preserve antigen-specific cytotoxic function"],"prefix":"10.3389","volume":"16","author":[{"given":"E.A.","family":"Zmievskaya","sequence":"first","affiliation":[{"name":"Institute of Fundamental Medicine and Biology, Kazan Federal University","place":["Kazan, 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