{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:32:52Z","timestamp":1789907572885,"version":"4.0.1"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Z99CL999999"],"award-info":[{"award-number":["Z99CL999999"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for many hematological malignancies. However, high relapse rates and limited accessibility remain significant challenges. We developed a 3-day streamlined process to address these limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>T-cells were isolated from whole blood collected from healthy donors via an automated density gradient separation that included a T-isopure\u2122 antibody cocktail, which isolates T-cells through negative selection. T-cells were activated then transduced with a lentiviral vector encoding a trispecific CAR. T-cells were cultured in G-Rex vessels and harvested at day 3 or day 7 for analysis. CAR expression and T-cell phenotype were assessed by flow cytometry and gene expression analysis. Functional activity was evaluated by measuring cytotoxicity and cytokine secretion following co-culture with target cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The T-isopure isolation enriched CD3\n                      <jats:sup>+<\/jats:sup>\n                      T-cells in whole blood from 18.9% to 88.5% of CD45\n                      <jats:sup>+<\/jats:sup>\n                      cells, with a mean recovery of 40.6%. RBCs were depleted with \u2265\u200999% efficiency, with monocytes and NK cells comprising the bulk of remaining CD45\n                      <jats:sup>+<\/jats:sup>\n                      cells. The 3-day manufacturing process produced T-cells with &gt;\u200995% viability, 53% transduction efficiency, and vector copy number\u2009&lt;\u20093 copies\/cell. Phenotypic analysis revealed a high proportion of stem\/central memory T-cells at both timepoints, with no significant differences observed. Cytotoxicity assays demonstrated strong and sustained killing of NALM6 tumor cells, comparable between both products. Gene expression profiling indicated that day 3 products were less differentiated, exhibiting a memory-like phenotype and reduced inflammatory signaling, further supported by protein analysis of culture supernatants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study establishes a rapid, GMP-compliant method for manufacturing polyfunctional, CAR T-cells directly from whole blood. The workflow outlined here achieved a potent, phenotypically favorable CAR T-cell product without compromising viability or cytotoxic function. Compared to the standard 7-day method, the 3-day approach resulted in expression of genes associated with a more stem-like phenotype while reducing manufacturing time and cost. This method may provide a practical alternative for decentralized CAR T-cell manufacturing, particularly in resource-limited settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08306-8","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:09:29Z","timestamp":1784128169000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of a 3-day manufacturing method to generate CD19-CD20-CD22 trispecific CAR T-cells from whole blood"],"prefix":"10.1186","volume":"24","author":[{"given":"Isabella","family":"Vignola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Prochazkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lipei","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Fuksenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarmila","family":"Sarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjian","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibeawuchi","family":"Oparaocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oxana","family":"Slessareva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Forrest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rimas","family":"Orentas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boro","family":"Dropulic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Somerville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Stroncek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah W.","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0135-0961","authenticated-orcid":false,"given":"Steven L.","family":"Highfill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"8306_CR1","doi-asserted-by":"crossref","unstructured":"Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3(95).","DOI":"10.1126\/scitranslmed.3002842"},{"issue":"4","key":"8306_CR2","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","volume":"11","author":"RC Sterner","year":"2021","unstructured":"Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69.","journal-title":"Blood Cancer J"},{"key":"8306_CR3","doi-asserted-by":"crossref","unstructured":"Mitra A, Barua A, Huang L, Ganguly S, Feng Q, He B. From bench to bedside: the history and progress of CAR T cell therapy. Front Immunol. 2023;14.","DOI":"10.3389\/fimmu.2023.1188049"},{"key":"8306_CR4","unstructured":"Cells CART. Engineering Patients\u2019 Immune Cells to Treat Their Cancers: National Cancer Institute; [updated February 26, 2025; cited 2025 June 23]. Available from: https:\/\/www.cancer.gov\/about-cancer\/treatment\/research\/car-t-cells."},{"issue":"5","key":"8306_CR5","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1056\/NEJMoa1709866","volume":"378","author":"L Maude Shannon","year":"2018","unstructured":"Maude Shannon L, Laetsch Theodore W, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018;378(5):439\u201348.","journal-title":"N Engl J Med"},{"issue":"1","key":"8306_CR6","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1056\/NEJMoa1804980","volume":"380","author":"SJ Schuster","year":"2019","unstructured":"Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019;380(1):45\u201356.","journal-title":"N Engl J Med"},{"issue":"26","key":"8306_CR7","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","volume":"377","author":"S Neelapu Sattva","year":"2017","unstructured":"Neelapu Sattva S, Locke Frederick L, Bartlett Nancy L, Lekakis Lazaros J, Miklos David B, Jacobson Caron A, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017;377(26):2531\u201344.","journal-title":"N Engl J Med"},{"key":"8306_CR8","doi-asserted-by":"crossref","unstructured":"Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma(ZUMA-1): a single-arm, multicentre, phase 1\u20132 trial. The Lancet Oncology.2019;20(1):31\u201342.","DOI":"10.1016\/S1470-2045(18)30864-7"},{"key":"8306_CR9","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.3389\/fimmu.2019.02711","volume":"10","author":"M Seif","year":"2019","unstructured":"Seif M, Einsele H, L\u00f6ffler J. CAR T Cells Beyond Cancer: Hope for Immunomodulatory Therapy of Infectious Diseases. Front Immunol. 2019;10:2711.","journal-title":"Front Immunol"},{"issue":"10","key":"8306_CR10","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1038\/nm.2446","volume":"17","author":"L Gattinoni","year":"2011","unstructured":"Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, et al. A human memory T cell subset with stem cell-like properties. Nat Med. 2011;17(10):1290\u20137.","journal-title":"Nat Med"},{"issue":"6","key":"8306_CR11","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/s43018-021-00207-7","volume":"2","author":"L Biasco","year":"2021","unstructured":"Biasco L, Izotova N, Rivat C, Ghorashian S, Richardson R, Guvenel A, et al. Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients. Nat Cancer. 2021;2(6):629\u201342.","journal-title":"Nat Cancer"},{"issue":"7","key":"8306_CR12","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1001\/jamaoncol.2018.0977","volume":"4","author":"I Hernandez","year":"2018","unstructured":"Hernandez I, Prasad V, Gellad WF. Total Costs of Chimeric Antigen Receptor T-Cell Immunotherapy. JAMA Oncol. 2018;4(7):994\u20136.","journal-title":"JAMA Oncol"},{"issue":"3","key":"8306_CR13","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.jcyt.2024.11.013","volume":"27","author":"R Traynor","year":"2024","unstructured":"Traynor R, Vignola I, Sarkar S, Prochazkova M, Cai Y, Shi R, et al. Efficient manufacturing of CAR-T cells from whole blood: a scalable approach to reduce costs and enhance accessibility in cancer therapy. Cytotherapy. 2024;27(3):400\u20139.","journal-title":"Cytotherapy"},{"key":"8306_CR14","doi-asserted-by":"crossref","unstructured":"Orentas RJ, Xiong Y, Xie Y, Zhu Z, Oparaocha I, Sleesareva O, et al. Technological and manufacturing innovation drive improved access to engineered T cell therapies. Med Reserach Archives. 2023;11(11).","DOI":"10.18103\/mra.v11i11.4759"},{"issue":"9","key":"8306_CR15","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1200\/JCO.22.01214","volume":"41","author":"T Wang","year":"2023","unstructured":"Wang T, Tang Y, Cai J, Wan X, Hu S, Lu X, et al. Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial. J Clin Oncol. 2023;41(9):1670\u201383.","journal-title":"J Clin Oncol"},{"issue":"8","key":"8306_CR16","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1001\/jamaoncol.2017.0184","volume":"3","author":"N Ahmed","year":"2017","unstructured":"Ahmed N, Brawley V, Hegde M, Bielamowicz K, Kalra M, Landi D, et al. HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 2017;3(8):1094\u2013101.","journal-title":"JAMA Oncol"},{"issue":"6","key":"8306_CR17","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/s43018-024-00749-6","volume":"5","author":"M Hegde","year":"2024","unstructured":"Hegde M, Navai S, DeRenzo C, Joseph SK, Sanber K, Wu M, et al. Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial. Nat Cancer. 2024;5(6):880\u201394.","journal-title":"Nat Cancer"},{"key":"8306_CR18","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1126\/scitranslmed.abc6401","volume":"13","author":"D Schneider","year":"2021","unstructured":"Schneider D, Xiong Y, Wu D, Hu P, Alabanza L, Steimle B, et al. Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models. Sci Transl Med. 2021;13:586.","journal-title":"Sci Transl Med"},{"key":"8306_CR19","doi-asserted-by":"crossref","unstructured":"Ying Xiong YX, Zhu Z, Oparaocha I, Sleesareva O, Dropuliv B, Rimas J. Orentas. Technological and manufacturing innovation drive improved access to engineered T cell therapies. Med Res Archives. 2023;11(11).","DOI":"10.18103\/mra.v11i11.4759"},{"key":"8306_CR20","doi-asserted-by":"crossref","unstructured":"Sheng M, Vick L, Collins C, Nielsen R, Tuscano JM, Orentas RJ, et al. editors. Developing and Characterizing the Anti-Tumor Efficacy of a Tri-Specific CAR T Cell Targeting CD19, CD20 and CD22. Blood; 2024. 2024\/11\/05.","DOI":"10.1182\/blood-2024-199366"},{"issue":"8","key":"8306_CR21","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/nri1413","volume":"4","author":"MJ Bevan","year":"2004","unstructured":"Bevan MJ. Helping the CD8\u2009+\u2009T-cell response. Nat Rev Immunol. 2004;4(8):595\u2013602.","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"8306_CR22","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.chembiol.2023.10.024","volume":"31","author":"IC Lane","year":"2024","unstructured":"Lane IC, Kembuan G, Carreiro J, Kann MC, Lin W, Bouffard AA, et al. Genetic retargeting of E3 ligases to enhance CAR T cell therapy. Cell Chem Biol. 2024;31(2):338\u2013. \u2013\u200948.e5.","journal-title":"Cell Chem Biol"},{"issue":"2","key":"8306_CR23","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.immuni.2018.01.006","volume":"48","author":"LK Smith","year":"2018","unstructured":"Smith LK, Boukhaled GM, Condotta SA, Mazouz S, Guthmiller JJ, Vijay R, et al. Interleukin-10 Directly Inhibits CD8(+) T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity. Immunity. 2018;48(2):299\u2013e3125.","journal-title":"Immunity"},{"issue":"2","key":"8306_CR24","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1007\/s13205-020-02549-y","volume":"11","author":"S Kumari","year":"2021","unstructured":"Kumari S, Arora M, Singh J, Chauhan SS, Kumar S, Chopra A. L-Selectin expression is associated with inflammatory microenvironment and favourable prognosis in breast cancer. 3 Biotech. 2021;11(2):38.","journal-title":"3 Biotech"},{"issue":"4","key":"8306_CR25","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1002\/eji.200636678","volume":"37","author":"CA Jansen","year":"2007","unstructured":"Jansen CA, Cruijsen CW, de Ruiter T, Nanlohy N, Willems N, Janssens-Korpela PL, et al. Regulated expression of the inhibitory receptor LAIR-1 on human peripheral T cells during T cell activation and differentiation. Eur J Immunol. 2007;37(4):914\u201324.","journal-title":"Eur J Immunol"},{"issue":"4","key":"8306_CR26","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.immuni.2025.01.016","volume":"58","author":"W Huai","year":"2025","unstructured":"Huai W, Yang K, Xing C, Song K, Lyu H, Williams NS, et al. OAS cross-activates RNase L intercellularly through cell-to-cell transfer of 2-5A to spread innate immunity. Immunity. 2025;58(4):797\u2013e8106.","journal-title":"Immunity"},{"issue":"4","key":"8306_CR27","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/imm.13163","volume":"159","author":"DC Y\u00e1nez","year":"2020","unstructured":"Y\u00e1nez DC, Ross S, Crompton T. The IFITM protein family in adaptive immunity. Immunology. 2020;159(4):365\u201372.","journal-title":"Immunology"},{"issue":"20","key":"8306_CR28","doi-asserted-by":"publisher","first-page":"11254","DOI":"10.1128\/JVI.00576-12","volume":"86","author":"S Zhou","year":"2012","unstructured":"Zhou S, Cerny AM, Fitzgerald KA, Kurt-Jones EA, Finberg RW. Role of interferon regulatory factor 7 in T cell responses during acute lymphocytic choriomeningitis virus infection. J Virol. 2012;86(20):11254\u201365.","journal-title":"J Virol"},{"issue":"2","key":"8306_CR29","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.jid.2023.08.006","volume":"144","author":"EJ Lee","year":"2024","unstructured":"Lee EJ, Kim JY, Yeo JH, Park S, Bae YJ, Kwon IJ, et al. ISG15\u2013USP18 Dysregulation by Oxidative Stress Promotes IFN-\u03b3 Secretion from CD8\u2009+\u2009T Cells in Vitiligo. J Invest Dermatology. 2024;144(2):273\u2013e8311.","journal-title":"J Invest Dermatology"},{"issue":"3","key":"8306_CR30","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.it.2023.01.002","volume":"44","author":"L Soriano-Baguet","year":"2023","unstructured":"Soriano-Baguet L, Brenner D. Metabolism and epigenetics at the heart of T cell function. Trends Immunol. 2023;44(3):231\u201344.","journal-title":"Trends Immunol"},{"issue":"4","key":"8306_CR31","doi-asserted-by":"publisher","first-page":"901","DOI":"10.4049\/jimmunol.2000228","volume":"205","author":"Z Qiu","year":"2020","unstructured":"Qiu Z, Khairallah C, Romanov G, Sheridan BS. Cutting Edge: Batf3 Expression by CD8 T Cells Critically Regulates the Development of Memory Populations. J Immunol. 2020;205(4):901\u20136.","journal-title":"J Immunol"},{"issue":"9","key":"8306_CR32","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1158\/2326-6066.CIR-17-0405","volume":"6","author":"S Ghassemi","year":"2018","unstructured":"Ghassemi S, Nunez-Cruz S, O\u2019Connor RS, Fraietta JA, Patel PR, Scholler J, et al. Reducing Ex Vivo Culture Improves the Antileukemic Activity of Chimeric Antigen Receptor (CAR) T Cells. Cancer Immunol Res. 2018;6(9):1100\u20139.","journal-title":"Cancer Immunol Res"},{"issue":"18","key":"8306_CR33","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1056\/NEJMoa2408771","volume":"392","author":"J Svoboda","year":"2025","unstructured":"Svoboda J, Landsburg DJ, Gerson J, Nasta SD, Barta SK, Chong EA, et al. Enhanced CAR T-Cell Therapy for Lymphoma after Previous Failure. N Engl J Med. 2025;392(18):1824\u201335.","journal-title":"N Engl J Med"},{"issue":"7","key":"8306_CR34","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/s41408-022-00694-6","volume":"12","author":"J Yang","year":"2022","unstructured":"Yang J, He J, Zhang X, Li J, Wang Z, Zhang Y, et al. Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study. Blood Cancer J. 2022;12(7):104.","journal-title":"Blood Cancer J"},{"issue":"9","key":"8306_CR35","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1158\/2159-8290.CD-22-1276","volume":"13","author":"MJ Dickinson","year":"2023","unstructured":"Dickinson MJ, Barba P, J\u00e4ger U, Shah NN, Blaise D, Briones J, et al. A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development. Cancer Discov. 2023;13(9):1982\u201397.","journal-title":"Cancer Discov"},{"issue":"6","key":"8306_CR36","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41408-022-00688-4","volume":"12","author":"C Zhang","year":"2022","unstructured":"Zhang C, He J, Liu L, Wang J, Wang S, Liu L, et al. Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia. Blood Cancer J. 2022;12(6):96.","journal-title":"Blood Cancer J"},{"issue":"2","key":"8306_CR37","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41551-021-00842-6","volume":"6","author":"S Ghassemi","year":"2022","unstructured":"Ghassemi S, Durgin JS, Nunez-Cruz S, Patel J, Leferovich J, Pinzone M, et al. Rapid manufacturing of non-activated potent CAR T cells. Nat Biomed Eng. 2022;6(2):118\u201328.","journal-title":"Nat Biomed Eng"},{"issue":"9","key":"8306_CR38","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1158\/2159-8290.CD-22-1276","volume":"13","author":"MJ Dickinson","year":"2023","unstructured":"Dickinson MJ, Barba P, Jager U, Shah NN, Blaise D, Briones J, et al. A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development. Cancer Discov. 2023;13(9):1982\u201397.","journal-title":"Cancer Discov"},{"issue":"10","key":"8306_CR39","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nrc3322","volume":"12","author":"L Gattinoni","year":"2012","unstructured":"Gattinoni L, Klebanoff CA, Restifo NP. Paths to stemness: building the ultimate antitumour T cell. Nat Rev Cancer. 2012;12(10):671\u201384.","journal-title":"Nat Rev Cancer"},{"issue":"12","key":"8306_CR40","doi-asserted-by":"publisher","first-page":"3324","DOI":"10.1002\/eji.201546000","volume":"45","author":"C Mathieu","year":"2015","unstructured":"Mathieu C, Beltra JC, Charpentier T, Bourbonnais S, Di Santo JP, Lamarre A, et al. IL-2 and IL-15 regulate CD8\u2009+\u2009memory T-cell differentiation but are dispensable for protective recall responses. Eur J Immunol. 2015;45(12):3324\u201338.","journal-title":"Eur J Immunol"},{"issue":"4","key":"8306_CR41","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nri2735","volume":"10","author":"WE Paul","year":"2010","unstructured":"Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10(4):225\u201335.","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"8306_CR42","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/nri2711","volume":"10","author":"M Saraiva","year":"2010","unstructured":"Saraiva M, O\u2019Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010;10(3):170\u201381.","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"8306_CR43","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1097\/CJI.0b013e31827806e6","volume":"35","author":"CA Klebanoff","year":"2012","unstructured":"Klebanoff CA, Gattinoni L, Restifo NP. Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy? J Immunother. 2012;35(9):651\u201360.","journal-title":"J Immunother"},{"key":"8306_CR44","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","volume":"29","author":"W Ouyang","year":"2011","unstructured":"Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol. 2011;29:71\u2013109.","journal-title":"Annu Rev Immunol"},{"issue":"6","key":"8306_CR45","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.coviro.2011.10.008","volume":"1","author":"JW Schoggins","year":"2011","unstructured":"Schoggins JW, Rice CM. Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol. 2011;1(6):519\u201325.","journal-title":"Curr Opin Virol"},{"issue":"3","key":"8306_CR46","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.cell.2015.12.032","volume":"164","author":"S Mostafavi","year":"2016","unstructured":"Mostafavi S, Yoshida H, Moodley D, LeBoit\u00e9 H, Rothamel K, Raj T, et al. Parsing the Interferon Transcriptional Network and Its Disease Associations. Cell. 2016;164(3):564\u201378.","journal-title":"Cell"},{"issue":"1","key":"8306_CR47","first-page":"103489","volume":"73","author":"M Ahmadi","year":"2025","unstructured":"Ahmadi M, Putnam N, Dotson M, Hayoun D, Padilla J, Fatima N, et al. Accelerating CAR T cell manufacturing with an automated next-day process. Curr Res Transl Med. 2025;73(1):103489.","journal-title":"Curr Res Transl Med"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08306-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08306-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08306-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:53:04Z","timestamp":1786521184000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08306-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8306"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08306-8","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"assertion":[{"value":"30 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Samples for this study were obtained from healthy donors in accordance with the Declaration of Helsinki, and as part of a National Institutes of Health Clinical Center institutional review board-approved protocol (protocol 99-CC-0168; Clinical Trials Registration, NCT00001846). Donors provided written informed consent, and blood samples were de-identified prior to distribution.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"923"}}