{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:42:51Z","timestamp":1792464171265,"version":"4.5.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T00:00:00Z","timestamp":1737763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T00:00:00Z","timestamp":1737763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved. This study tested whether the overexpression of Lectin-like transcript 1 (LLT1), an NK cell inhibitory ligand, in T cell receptor (TCR) and HLA-I\/II disrupted universal CD38-targeting CAR-T cells could prevent rejection by allogeneic NK cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We generated CD38-targeting universal CAR-T cells by transducing T cells with lentiviruses encoding the CD38 CAR and LLT1 constructs. T cells were subjected to CD38, TCR, HLA-I, and HLA-II gene knockdown using CRISPR\/Cas9, followed by lentiviral transduction. We performed cytotoxicity, proliferation, and cytokine assays to evaluate the functionality of universal chimeric antigen receptor-T cell (UCAR-T) cells and conducted in vitro and in vivo assays, including allogeneic responses and RNA sequencing, to assess their resistance to allogeneic T and NK cells, anti-leukemia efficacy, and persistence in treating hematologic malignancies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Genetic editing of CD38 universal CAR-T cells, including CD38, T cell receptor alpha constant (TRAC), beta-2-microglobulin (B2M), and class II major histocompatibility complex transactivator (CIITA) knockdowns, was successfully achieved. In vitro, LLT1 overexpression boosted CAR-T cell proliferation and antitumor activity, leading to a transcriptional signature characterized by elevated stemness-related markers (\n                      <jats:italic>SELL<\/jats:italic>\n                      ,\u00a0\n                      <jats:italic>BCL6<\/jats:italic>\n                      ,\n                      <jats:italic>TCF7<\/jats:italic>\n                      , and\n                      <jats:italic>CD27<\/jats:italic>\n                      ) and increased levels of IL-10 and other cytokines. It also effectively mitigates rejection by allogeneic NK and T cells. In a humanized T-cell acute lymphoblastic leukemia (T-ALL) model, CD38 allogeneic universal CAR-T cells demonstrated superior survival rates and tumor clearance with reduced inflammatory responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>According to these results, LLT1 overexpression enhances UCAR-T cell activity and prevents allogeneic rejection, providing essential insights for the development of universal CAR-T cell therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-025-03273-2","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T22:43:51Z","timestamp":1737758631000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells"],"prefix":"10.1186","volume":"44","author":[{"given":"Shuxian","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjie","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erlie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7675-3600","authenticated-orcid":false,"given":"Xiaoming","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuechen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,25]]},"reference":[{"key":"3273_CR1","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/S1470-2045(23)00436-9","volume":"24","author":"J Pan","year":"2023","unstructured":"Pan J, Tang K, Luo Y, Seery S, Tan Y, Deng B, et al. Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2023;24:1229\u201341.","journal-title":"Lancet Oncol"},{"key":"3273_CR2","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1056\/NEJMoa1407222","volume":"371","author":"SL Maude","year":"2014","unstructured":"Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N Engl J Med. 2014;371:1507\u201317.","journal-title":"N Engl J Med"},{"key":"3273_CR3","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1056\/NEJMoa1215134","volume":"368","author":"SA Grupp","year":"2013","unstructured":"Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia. N Engl J Med. 2013;368:1509\u201318.","journal-title":"N Engl J Med"},{"key":"3273_CR4","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1172\/JCI85309","volume":"126","author":"CJ Turtle","year":"2016","unstructured":"Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Investig. 2016;126:2123\u201338.","journal-title":"J Clin Investig"},{"key":"3273_CR5","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1182\/blood-2005-11-007237","volume":"108","author":"J Carrasco","year":"2006","unstructured":"Carrasco J, Godelaine D, Van Pel A, Boon T, Van Der Bruggen P. CD45RA on human CD8 T cells is sensitive to the time elapsed since the last antigenic stimulation. Blood. 2006;108:2897\u2013905.","journal-title":"Blood"},{"key":"3273_CR6","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1172\/JCI32103","volume":"118","author":"C Berger","year":"2008","unstructured":"Berger C, Jensen MC, Lansdorp PM, Gough M, Elliott C, Riddell SR. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Investig. 2008;118:294\u2013305.","journal-title":"J Clin Investig"},{"key":"3273_CR7","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.1182\/blood-2021-146038","volume":"138","author":"SS Neelapu","year":"2021","unstructured":"Neelapu SS, Nath R, Munoz J, Tees M, Miklos DB, Frank MJ, et al. ALPHA Study: ALLO-501 Produced Deep and Durable Responses in Patients with Relapsed\/Refractory Non-Hodgkin\u2019s Lymphoma Comparable to Autologous CAR T. Blood. 2021;138:3878\u20133878.","journal-title":"Blood"},{"key":"3273_CR8","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1182\/blood-2021-150609","volume":"138","author":"BD Shah","year":"2021","unstructured":"Shah BD, Jacobson C, Solomon SR, Jain N, Johnson MC, Vainorius M, et al. Allogeneic CAR-T PBCAR0191 with Intensified Lymphodepletion Is Highly Active in Patients with Relapsed\/Refractory B-Cell Malignancies. Blood. 2021;138:302\u2013302.","journal-title":"Blood"},{"key":"3273_CR9","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/ni0508-477","volume":"9","author":"K K\u00e4rre","year":"2008","unstructured":"K\u00e4rre K. Natural killer cell recognition of missing self. Nat Immunol. 2008;9:477\u201380.","journal-title":"Nat Immunol"},{"key":"3273_CR10","doi-asserted-by":"crossref","unstructured":"Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K, et al. Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood. 1999;94:333\u20139.","DOI":"10.1182\/blood.V94.1.333.413a31_333_339"},{"key":"3273_CR11","doi-asserted-by":"crossref","unstructured":"Li W, Zhu X, Xu Y, Chen J, Zhang H, Yang Z, et al. Simultaneous editing of TCR, HLA-I\/II and HLA-E resulted in enhanced universal CAR-T resistance to allo-rejection.\u00a0Front Immunol. 2022;13:1052717.","DOI":"10.3389\/fimmu.2022.1052717"},{"key":"3273_CR12","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41421-024-00646-3","volume":"10","author":"X Liu","year":"2024","unstructured":"Liu X, Zuo F, Song J, Tang L, Wang X, Liu X, et al. Immune checkpoints HLA-E:CD94-NKG2A and HLA-C:KIR2DL1 complementarily shield circulating tumor cells from NK-mediated immune surveillance. Cell Discov. 2024;10:16.","journal-title":"Cell Discov"},{"key":"3273_CR13","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1158\/1078-0432.CCR-20-3863","volume":"27","author":"Y Hu","year":"2021","unstructured":"Hu Y, Zhou Y, Zhang M, Ge W, Li Y, Yang L, et al. CRISPR\/Cas9-engineered universal CD19\/CD22 dual-targeted CAR-T cell therapy for relapsed\/refractory B-cell acute lymphoblastic leukemia. Clin Cancer Res. 2021;27:2764\u201372.","journal-title":"Clin Cancer Res"},{"key":"3273_CR14","doi-asserted-by":"crossref","unstructured":"Aldemir H, Prod\u2019homme V, Dumaurier M-J, Retiere C, Poupon G, Cazareth J, et al. Cutting Edge: Lectin-Like Transcript 1 Is a Ligand for the CD161 Receptor. J Immunol. 2005;175:7791\u20135.","DOI":"10.4049\/jimmunol.175.12.7791"},{"key":"3273_CR15","doi-asserted-by":"publisher","first-page":"7796","DOI":"10.4049\/jimmunol.175.12.7796","volume":"175","author":"DB Rosen","year":"2005","unstructured":"Rosen DB, Bettadapura J, Alsharifi M, Mathew PA, Warren HS, Lanier LL. Cutting Edge: Lectin-Like Transcript-1 Is a Ligand for the Inhibitory Human NKR-P1A Receptor. J Immunol. 2005;175:7796\u20139.","journal-title":"J Immunol"},{"key":"3273_CR16","doi-asserted-by":"publisher","first-page":"616","DOI":"10.3324\/haematol.2015.137620","volume":"101","author":"E Drent","year":"2016","unstructured":"Drent E, Groen RWJ, Noort WA, Themeli M, van Bueren JJL, Parren PWHI, et al. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica. 2016;101:616\u201325.","journal-title":"Haematologica"},{"key":"3273_CR17","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1002\/ajh.24571","volume":"92","author":"F Zaja","year":"2017","unstructured":"Zaja F, Tabanelli V, Agostinelli C, Calleri A, Chiappella A, Varettoni M, et al. CD38, BCL-2, PD-1, and PD-1L expression in nodal peripheral T-cell lymphoma: Possible biomarkers for novel targeted therapies? Am J Hematol. 2017;92:E1-2.","journal-title":"Am J Hematol"},{"key":"3273_CR18","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0145-2126(99)00147-2","volume":"24","author":"A Keyhani","year":"2000","unstructured":"Keyhani A, Huh YO, Jendiroba D, Pagliaro L, Cortez J, Pierce S, et al. Increased CD38 expression is associated with favorable prognosis in adult acute leukemia. Leuk Res. 2000;24:153\u20139.","journal-title":"Leuk Res"},{"key":"3273_CR19","doi-asserted-by":"crossref","unstructured":"Cui Q, Qian C, Xu N, Kang L, Dai H, Cui W, et al. CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.\u00a0J Hematol Oncol. 2021;14:82.","DOI":"10.1186\/s13045-021-01092-4"},{"key":"3273_CR20","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s41423-019-0355-5","volume":"17","author":"Y Guo","year":"2020","unstructured":"Guo Y, Feng K, Tong C, Jia H, Liu Y, Wang Y, et al. Efficiency and side effects of anti-CD38 CAR T cells in an adult patient with relapsed B-ALL after failure of bi-specific CD19\/CD22 CAR T cell treatment. Cell Mol Immunol. 2020;17:430\u20132.","journal-title":"Cell Mol Immunol"},{"key":"3273_CR21","doi-asserted-by":"crossref","unstructured":"Chen Y, Xu Y, Li H, Sun T, Cao X, Wang Y, et al. A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia. New England Journal of Medicine [Internet]. 2024;390:2178\u201390.","DOI":"10.1056\/NEJMoa2400409"},{"key":"3273_CR22","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.jgg.2019.06.007","volume":"46","author":"Z Gao","year":"2019","unstructured":"Gao Z, Tong C, Wang Y, Chen D, Wu Z, Han W. Blocking CD38-driven fratricide among T cells enables effective antitumor activity by CD38-specific chimeric antigen receptor T cells. J Genet Genomics. 2019;46:367\u201377.","journal-title":"J Genet Genomics"},{"key":"3273_CR23","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1158\/2326-6066.CIR-18-0508","volume":"8","author":"Y Kagoya","year":"2020","unstructured":"Kagoya Y, Guo T, Yeung B, Saso K, Anczurowski M, Wang CH, et al. Genetic ablation of HLA class I, class II, and the T-cell receptor enables allogeneic T cells to be used for adoptive T-cell therapy. Cancer Immunol Res. 2020;8:926\u201336.","journal-title":"Cancer Immunol Res"},{"key":"3273_CR24","doi-asserted-by":"publisher","first-page":"68650","DOI":"10.18632\/oncotarget.11896","volume":"7","author":"SO Mathew","year":"2016","unstructured":"Mathew SO, Chaudhary P, Powers SB, Vishwanatha JK, Mathew PA. Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction. Oncotarget. 2016;7:68650\u201361.","journal-title":"Oncotarget"},{"key":"3273_CR25","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1172\/JCI24480","volume":"115","author":"L Gattinoni","year":"2005","unstructured":"Gattinoni L, Klebanoff CA, Palmer DC, Wrzesinski C, Kerstann K, Yu Z, et al. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J Clin Investig. 2005;115:1616\u201326.","journal-title":"J Clin Investig"},{"key":"3273_CR26","doi-asserted-by":"crossref","unstructured":"Neefjes J, Jongsma MLM, Paul P, Bakke O. Towards a systems understanding of MHC class I and MHC class II antigen presentation.\u00a0Nat Rev Immunol. 2011;11:823\u201336.","DOI":"10.1038\/nri3084"},{"key":"3273_CR27","doi-asserted-by":"crossref","unstructured":"Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: from molecular mechanisms to human therapy.\u00a0Nat Rev Immunol. 2018;18:648\u201359.","DOI":"10.1038\/s41577-018-0046-y"},{"key":"3273_CR28","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.immuni.2010.08.002","volume":"33","author":"X Zhou","year":"2010","unstructured":"Zhou X, Yu S, Zhao DM, Harty JT, Badovinac VP, Xue HH. Differentiation and Persistence of Memory CD8+ T Cells Depend on T Cell Factor 1. Immunity. 2010;33:229\u201340.","journal-title":"Immunity"},{"key":"3273_CR29","doi-asserted-by":"crossref","unstructured":"Wei W, Mu S, Han Y, Chen Y, Kuang Z, Wu X, et al. Gpr174 Knockout Alleviates DSS-Induced Colitis via Regulating the Immune Function of Dendritic Cells.\u00a0Front Immunol. 2022;13:841254.","DOI":"10.3389\/fimmu.2022.841254"},{"key":"3273_CR30","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.immuni.2019.03.020","volume":"50","author":"W Ouyang","year":"2019","unstructured":"Ouyang W, O\u2019Garra A. IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation. Immunity. 2019;50:871\u201391.","journal-title":"Immunity"},{"key":"3273_CR31","doi-asserted-by":"publisher","first-page":"3527","DOI":"10.1073\/pnas.0308304101","volume":"101","author":"JR Carlyle","year":"2004","unstructured":"Carlyle JR, Jamieson AM, Gasser S, Clingan CS, Arase H, Raulet DH. Missing self-recognition of Ocil\/Clr-b by inhibitory NKR-P1 natural killer cell receptors. Proc Natl Acad Sci U S A. 2004;101:3527\u201332.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3273_CR32","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1038\/s41422-022-00721-y","volume":"32","author":"Y Hu","year":"2022","unstructured":"Hu Y, Zhou Y, Zhang M, Zhao H, Wei G, Ge W, et al. Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed\/refractory CD7-positive hematological malignancies: a phase I clinical study. Cell Res. 2022;32:995\u20131007.","journal-title":"Cell Res"},{"key":"3273_CR33","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1182\/blood-2010-07-294520","volume":"117","author":"CHJ Lamers","year":"2011","unstructured":"Lamers CHJ, Willemsen R, Van Elzakker P, Van Steenbergen-Langeveld S, Broertjes M, Oosterwijk-Wakka J, et al. Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells. Blood. 2011;117:72\u201382.","journal-title":"Blood"},{"key":"3273_CR34","doi-asserted-by":"crossref","unstructured":"Chen S, Zhang Y, Fang C, Zhang N, Wang Y, Chen R, et al. Donor-derived and off-the-shelf allogeneic anti-CD19 CAR T-cell therapy for R\/R ALL and NHL: A systematic review and meta-analysis. Critical reviews in oncology\/hematology. 2022;179:103807.","DOI":"10.1016\/j.critrevonc.2022.103807"},{"key":"3273_CR35","doi-asserted-by":"crossref","unstructured":"Zhang Y, Fang H, Wang G, Yuan G, Dong R, Luo J, et al. Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells.\u00a0Nat Commun. 2023;14:8491.","DOI":"10.1038\/s41467-023-44176-0"},{"key":"3273_CR36","doi-asserted-by":"crossref","unstructured":"1.Jo S, Das S, Williams A, Chretien AS, Pagliardini T, le Roy A, et al. Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing.\u00a0Nat Commun. 2022;13:3453.","DOI":"10.1038\/s41467-022-30896-2"},{"key":"3273_CR37","doi-asserted-by":"crossref","unstructured":"Liu D, Tian S, Zhang K, Xiong W, Lubaki NM, Chen Z, et al. Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV. Protein Cell. Higher Education Press; 2017;861\u201377.","DOI":"10.1007\/s13238-017-0415-5"},{"key":"3273_CR38","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41587-020-0601-5","volume":"39","author":"F Mo","year":"2021","unstructured":"Mo F, Watanabe N, McKenna MK, Hicks MJ, Srinivasan M, Gomes-Silva D, et al. Engineered off-the-shelf therapeutic T cells resist host immune rejection. Nat Biotechnol. 2021;39:56\u201363.","journal-title":"Nat Biotechnol"},{"key":"3273_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111423","volume":"40","author":"R Chimienti","year":"2022","unstructured":"Chimienti R, Baccega T, Torchio S, Manenti F, Pellegrini S, Cospito A, et al. Engineering of immune checkpoints B7\u2013H3 and CD155 enhances immune compatibility of MHC-I-\/- iPSCs for \u03b2 cell replacement. Cell Rep. 2022;40: 111423.","journal-title":"Cell Rep"},{"key":"3273_CR40","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.immuni.2016.07.013","volume":"45","author":"S Chen","year":"2016","unstructured":"Chen S, Yang M, Du J, Li D, Li Z, Cai C, et al. The Self-Specific Activation Receptor SLAM Family Is Critical for NK Cell Education. Immunity. 2016;45:292\u2013304.","journal-title":"Immunity"},{"key":"3273_CR41","doi-asserted-by":"crossref","unstructured":"Hu X, Manner K, DeJesus R, White K, Gattis C, Ngo P, et al. Hypoimmune anti-CD19 chimeric antigen receptor T cells provide lasting tumor control in fully immunocompetent allogeneic humanized mice.\u00a0Nat Commun. 2023;14:2020.","DOI":"10.1038\/s41467-023-37785-2"},{"key":"3273_CR42","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1002\/eji.202049107","volume":"51","author":"Y Guo","year":"2021","unstructured":"Guo Y, Xu B, Wu Z, Bo J, Tong C, Chen D, et al. Mutant B2M-HLA-E and B2M-HLA-G fusion proteins protects universal chimeric antigen receptor-modified T cells from allogeneic NK cell-mediated lysis. Eur J Immunol. 2021;51:2513\u201321.","journal-title":"Eur J Immunol"},{"key":"3273_CR43","doi-asserted-by":"crossref","unstructured":"Zhao Y, Chen J, Andreatta M, Feng B, Xie YQ, Wenes M, et al. IL-10-expressing CAR T cells resist dysfunction and mediate durable clearance of solid tumors and metastases.\u00a0Nat Biotechnol. 2024;42:1693\u2013704.","DOI":"10.1038\/s41587-023-02060-8"},{"key":"3273_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2014.16","volume-title":"Stem memory T cells (TSCM)\u2014their role in cancer and HIV immunotherapies","author":"JK Flynn","year":"2014","unstructured":"Flynn JK, Gorry PR. Stem memory T cells (TSCM)-their role in cancer and HIV immunotherapies. Clinical & translational immunology. 2014;3:e20."},{"key":"3273_CR45","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1152\/physrev.00035.2007","volume":"88","author":"F Malavasi","year":"2008","unstructured":"Malavasi F, Deaglio S, Funaro A, Ferrero E, Horenstein AL, Ortolan E, et al. Evolution and function of the ADP ribosyl cyclase\/CD38 gene family in physiology and pathology. Physiol Rev. 2008;88:841\u201386.","journal-title":"Physiol Rev"},{"key":"3273_CR46","doi-asserted-by":"crossref","unstructured":"Huang Y, Shao M, Teng X, Si X, Wu L, Jiang P, et al. Inhibition of CD38 enzymatic activity enhances CAR-T cell immune-therapeutic efficacy by repressing glycolytic metabolism. Cell Reports Medicine. 2024;5:101400.","DOI":"10.1016\/j.xcrm.2024.101400"},{"key":"3273_CR47","doi-asserted-by":"crossref","unstructured":"Veliz K, Shen F, Shestova O, Shestov M, Shestov A, Sleiman S, et al. Deletion of CD38 enhances CD19 chimeric antigen receptor T cell function. Molecular therapy Oncology. 2024;32:200819.","DOI":"10.1016\/j.omton.2024.200819"},{"key":"3273_CR48","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1309\/74R4TB90BUWH27JX","volume":"121","author":"P Lin","year":"2004","unstructured":"Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121:482\u20138.","journal-title":"Am J Clin Pathol"},{"key":"3273_CR49","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1182\/blood.V94.6.1840","volume":"94","author":"RN Damle","year":"1999","unstructured":"Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94:1840\u20137.","journal-title":"Blood"},{"key":"3273_CR50","doi-asserted-by":"crossref","unstructured":"Xiao X, Huang S, Chen S, Wang Y, Sun Q, Xu X, et al. Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies.\u00a0J Exp Clin Cancer Res. 2021;40:367.","DOI":"10.1186\/s13046-021-02148-6"},{"key":"3273_CR51","doi-asserted-by":"crossref","unstructured":"Jin X, Cao Y, Wang L, Sun R, Cheng L, He X, et al. HLA-matched and HLA-haploidentical allogeneic CD19-directed chimeric antigen receptor T-cell infusions are feasible in relapsed or refractory B-cell acute lymphoblastic leukemia before hematopoietic stem cell transplantation. Leukemia. 2020;34:909\u201313.","DOI":"10.1038\/s41375-019-0610-x"},{"key":"3273_CR52","doi-asserted-by":"crossref","unstructured":"Chuprin J, Buettner H, Seedhom MO, Greiner DL, Keck JG, Ishikawa F, et al. Humanized mouse models for immuno-oncology research.\u00a0Nat Rev Clin Oncol. 2023;20:192\u2013206.","DOI":"10.1038\/s41571-022-00721-2"},{"key":"3273_CR53","doi-asserted-by":"crossref","unstructured":"Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research.\u00a0Nat Rev Immunol. 2007;7:118\u201330.","DOI":"10.1038\/nri2017"}],"container-title":["Journal of Experimental &amp; Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-025-03273-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-025-03273-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-025-03273-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T22:44:08Z","timestamp":1737758648000},"score":1,"resource":{"primary":{"URL":"https:\/\/jeccr.biomedcentral.com\/articles\/10.1186\/s13046-025-03273-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,25]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3273"],"URL":"https:\/\/doi.org\/10.1186\/s13046-025-03273-2","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,25]]},"assertion":[{"value":"12 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Peripheral blood samples were collected from healthy donors at the Tianjin Blood Centre, with informed consent and ethical approval. The Ethical Committee of Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, China has evaluated and approved all the experimental protocols and animal use procedure (approval number: IHCAMS-DWLL-NKRDP2021009-2).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25"}}