{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T21:01:45Z","timestamp":1785013305590,"version":"3.55.0"},"reference-count":18,"publisher":"Begell House","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Crit Rev Oncog"],"published-print":{"date-parts":[[2026]]},"abstract":"<p>CAR T cell therapy, pioneered by Prof. Zelig Eshhar, has transformed hematologic malignancies but faces significant barriers in solid tumors, including poor infiltration, toxicity, and cytokine release syndrome. This perspective explores CAR T cell\u2013derived extracellular vesicles (CAR T EVs) as an emerging platform that extends Eshhar's vision by delivering CAR-mediated cytotoxicity with enhanced tumor penetration, physiological barrier, and reduced immunogenicity. EVs carry functional CARs as immunomodulatory cargo, enabling precise antigen targeting without cellular proliferation risks. Key advantages and challenges are reviewed. Building on Eshhar's foundational work, CAR T EVs represent a nanotechnology-immunotherapy alternative.<\/p>","DOI":"10.1615\/critrevoncog.2026063206","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T19:47:17Z","timestamp":1770061637000},"page":"1-4","source":"Crossref","is-referenced-by-count":0,"title":["Review Article: The Evolution and Future of Immunotherapy: The Promise of CAR T Cell-\u0080\u0093Derived Extracellular Vesicles"],"prefix":"10.1615","volume":"31","author":[{"given":"Anat","family":"Aharon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat Globerson","family":"Levin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"613","reference":[{"key":"2","doi-asserted-by":"crossref","unstructured":"Asari K, Chelvaretnam S, Mom KT, Bhuiyan S, Pham Q, Fitri A, Palma C, Shojaee M, Khanabdali R, Hinch L, Rice G. Enhancing chimeric antigen receptor-extracellular vesicles (CAR-EV) technology: The future of cancer therapy. J Vis Exp. 2025 Sep 19(223).","DOI":"10.3791\/68726"},{"key":"3","doi-asserted-by":"crossref","unstructured":"Globerson Levin A, Riviere I, Eshhar Z, Sadelain M. CAR T cells: Building on the CD19 paradigm. Eur J Immunol. 2021;51(9):2151-63.","DOI":"10.1002\/eji.202049064"},{"key":"4","doi-asserted-by":"crossref","unstructured":"Eshhar Z. From the mouse cage to human therapy: A personal perspective of the emergence of T-bodies\/chimeric antigen receptor T cells. Hum Gene Ther. 2014;25(9):773-8.","DOI":"10.1089\/hum.2014.2532"},{"key":"5","doi-asserted-by":"crossref","unstructured":"Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A. 1993;90(2):720-4.","DOI":"10.1073\/pnas.90.2.720"},{"key":"6","doi-asserted-by":"crossref","unstructured":"Aharon A, Horn G, Bar-Lev TH, Zagagi Yohay E, Waks T, Levin M, Deshet Unger N, Avivi I, Globerson Levin A. Extracellular vesicles derived from chimeric antigen receptor-T cells: A potential therapy for cancer. Hum Gene Ther. 2021;32(19-20):1224-41.","DOI":"10.1089\/hum.2021.192"},{"key":"7","doi-asserted-by":"crossref","unstructured":"Wang JS, Schellenberg SJ, Demeros A, Lin AY. Exosomes in review: A new frontier in CAR-T cell therapies. Neoplasia. 2025;62:101147.","DOI":"10.1016\/j.neo.2025.101147"},{"key":"8","doi-asserted-by":"crossref","unstructured":"De Sousa KP, Rossi I, Abdullahi M, Ramirez MI, Stratton D, Inal JM. Isolation and characterization of extracellular vesicles and future directions in diagnosis and therapy. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2023;15(1):e1835.","DOI":"10.1002\/wnan.1835"},{"key":"9","doi-asserted-by":"crossref","unstructured":"Turturici G, Tinnirello R, Sconzo G, Geraci F. Extracellular membrane vesicles as a mechanism of cell-to-cell communication: Advantages and disadvantages. Am J Physiol Cell Physiol. 2014;306(7):C621-33.","DOI":"10.1152\/ajpcell.00228.2013"},{"key":"10","doi-asserted-by":"crossref","unstructured":"Teng F, Fussenegger M. Shedding light on extracellular vesicle biogenesis and bioengineering. Adv Sci. 2020;8(1):2003505.","DOI":"10.1002\/advs.202003505"},{"key":"11","doi-asserted-by":"crossref","unstructured":"Sani F, Shojaei S, Tabatabaei SA, Khorraminejad-Shirazi M, Latifi M, Sani M, Azarpira N. CAR-T cell-derived exosomes: A new perspective for cancer therapy. Stem Cell Res Ther. 2024;15(1):174.","DOI":"10.1186\/s13287-024-03783-4"},{"key":"12","doi-asserted-by":"crossref","unstructured":"Fu W, Lei C, Liu S, Cui Y, Wang C, Qian K, Li T, Shen Y, Fan X, Lin F, Ding M. CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity. Nat Commun. 2019;10(1):4355.","DOI":"10.1038\/s41467-019-12321-3"},{"key":"13","doi-asserted-by":"crossref","unstructured":"Tang XJ, Sun XY, Huang KM, Zhang L, Yang ZS, Zou DD, Wang B, Warnock GL, Dai LJ, Luo J. Therapeutic potential of CAR-T cell-derived exosomes: A cell-free modality for targeted cancer therapy. Oncotarget. 2015;6(42):44179.","DOI":"10.18632\/oncotarget.6175"},{"key":"14","doi-asserted-by":"crossref","unstructured":"Aharon A, Spector P, Ahmad RS, Horrany N, Sabbach A, Brenner B, Aharon-Peretz J. Extracellular vesicles of Alzheimer's disease patients as a biomarker for disease progression. Mol Neurobiol. 2020;57(10):4156-69.","DOI":"10.1007\/s12035-020-02013-1"},{"key":"15","doi-asserted-by":"crossref","unstructured":"Moon GJ, Sung JH, Kim DH, Kim EH, Cho YH, Son JP, Cha JM, Bang OY. Application of mesenchymal stem cell-derived extracellular vesicles for stroke: Biodistribution and microRNA study. Transl Stroke Res. 2019;10(5):509-21.","DOI":"10.1007\/s12975-018-0668-1"},{"key":"16","doi-asserted-by":"crossref","unstructured":"Yaacoub S, Vannoy E, Maslova S, Haffey A, Khorsandi K, Sheybani N, Haydar D. CAR-T cell therapy in brain malignancies: Obstacles in the face of cellular trafficking and persistence. Front Immunol. 2025;16:1596499.","DOI":"10.3389\/fimmu.2025.1596499"},{"key":"17","doi-asserted-by":"crossref","unstructured":"Basyoni AE, Atta A, Salem MM, Mohamed TM. Harnessing exosomes for targeted drug delivery systems to combat brain cancer. Cancer Cell Int. 2025;25(1):150.","DOI":"10.1186\/s12935-025-03731-z"},{"key":"18","doi-asserted-by":"crossref","unstructured":"Kang M, Jordan V, Blenkiron C, Chamley LW. Biodistribution of extracellular vesicles following administration into animals: A systematic review. J Extracell Vesicles. 2021;10(8):e12085.","DOI":"10.1002\/jev2.12085"},{"key":"19","doi-asserted-by":"crossref","unstructured":"Liu J, Nordin JZ, McLachlan AJ, Chrzanowski W. Extracellular vesicles as the next-generation modulators of pharmacokinetics and pharmacodynamics of medications and their potential as adjuvant therapeutics. Clin Transl Med. 2024;14(8):e70002.","DOI":"10.1002\/ctm2.70002"}],"container-title":["Critical Reviews\u2122 in Oncogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.dl.begellhouse.com\/download\/article\/325717bc0f5fac26\/CRO-63206.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T20:33:55Z","timestamp":1785011635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.dl.begellhouse.com\/journals\/439f422d0783386a,5a518e4904bba712,325717bc0f5fac26.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1615\/critrevoncog.2026063206","relation":{},"ISSN":["0893-9675"],"issn-type":[{"value":"0893-9675","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]}}}