{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:37:47Z","timestamp":1793230667914,"version":"4.5.0"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    CAR T-cell therapy has become a transformative modality in oncology, demonstrating sustained clinical efficacy in hematologic malignancies. Recent investigations have expanded its potential beyond cancer to immune-mediated disorders, including autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus, as well as chronic viral infections including HIV and hepatitis B. This review examines the mechanistic foundations of CAR-T cells, advances in universal and allogeneic engineering strategies designed to mitigate graft-versus-host disease and host rejection, and emerging\n                    <jats:italic>in vivo<\/jats:italic>\n                    gene-delivery platforms that aim to bypass conventional ex vivo manufacturing. We further evaluate safety-control architectures, including logic-gated and inducible systems, and discuss translational barriers related to scalability, manufacturing standardization, and long-term immune durability. While technological innovations in genome editing, synthetic biology, and computational design continue to refine CAR-T platforms, substantial biological and logistical challenges remain. A critical synthesis of these evolving strategies is necessary to distinguish incremental optimization from paradigm-shifting advances and to define the future trajectory of CAR-based immunotherapy across oncology and immune-mediated diseases.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1802718","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:17:22Z","timestamp":1774369042000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Advancements and expanding applications of CAR-T cell therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiang","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medicine, Shanghai University","place":["Shanghai, China"]},{"name":"Institute of Artificial Intelligence and Biomanufacturing, School of Medicine, Shanghai University","place":["Shanghai, China"]},{"name":"Shanghai Tenth People\u2019s Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-jie","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University","place":["Shanghai, China"]},{"name":"Institute of Artificial Intelligence and Biomanufacturing, School of Medicine, Shanghai University","place":["Shanghai, China"]},{"name":"Shanghai Tenth People\u2019s Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-wei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University","place":["Shanghai, China"]},{"name":"Institute of Artificial Intelligence and Biomanufacturing, School of Medicine, Shanghai University","place":["Shanghai, China"]},{"name":"Shanghai Tenth People\u2019s Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Gang","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, Shanghai University","place":["Shanghai, China"]},{"name":"Institute of Artificial Intelligence and Biomanufacturing, School of Medicine, Shanghai University","place":["Shanghai, China"]},{"name":"Shanghai Tenth People\u2019s Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-04-839217","article-title":"Translating anti-cd19 car T-cell therapy into clinical practice for relapsed\/refractory diffuse large B-cell lymphoma","volume":"132","author":"Chow","year":"2018","journal-title":"Blood J Am Soc Hematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"New Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1007\/s44178-024-00117-5","article-title":"CAR-T cell therapy shines as a beam of hope in the fight against acute leukemia","volume":"3","author":"Sun","year":"2024","journal-title":"Holist Integ Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s40364-025-00755-5","article-title":"Nanobody-enhanced chimeric antigen receptor T-cell therapy: overcoming barriers in solid tumors with vhh and vnar-based constructs","volume":"13","author":"Guo","year":"2025","journal-title":"biomark Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1007\/s44178-025-00205-0","article-title":"Breaking barriers: the emerging promise of CAR-T cell therapy in solid tumors","volume":"4","author":"Nie","year":"2025","journal-title":"Holist Integ Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/s13045-025-01744-9","article-title":"Challenges and limitations of chimeric antigen receptor T-cell therapies in solid tumors: why are approvals restricted to hematologic Malignancies","volume":"18","author":"Vo","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00940","article-title":"T-cell compartmentalization and functional adaptation in autoimmune inflammation: lessons from pediatric rheumatic diseases","volume":"10","author":"Mijnheer","year":"2019","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/mdr2.70007","article-title":"Breaking boundaries: chronic diseases and the frontiers of immune microenvironments","volume":"1","author":"Li","year":"2025","journal-title":"Med Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)02265-7","article-title":"Treatment of cns systemic lupus erythematosus with cd19 car T cells","volume":"404","author":"Hagen","year":"2024","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1604174","article-title":"Car T-cells meet autoimmune neurological diseases: A new dawn for therapy","volume":"16","author":"Chinas","year":"2025","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12943-022-01559-z","article-title":"Engineering the next-generation of car T-cells with crispr-cas9 gene editing","volume":"21","author":"Dimitri","year":"2022","journal-title":"Mol Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv439","article-title":"Chimeric antigen receptors modified T-cells for cancer therapy","volume":"108","author":"Dai","year":"2016","journal-title":"J Natl Cancer Inst"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2559","article-title":"Combined cd28 and 4-1bb costimulation potentiates affinity-tuned chimeric antigen receptor\u2013engineered T cells","volume":"25","author":"Drent","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00530-z","article-title":"A comparison of chimeric antigen receptors containing cd28 versus 4-1bb costimulatory domains","volume":"18","author":"Cappell","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.210","article-title":"Chimeric antigen receptors combining 4-1bb and cd28 signaling domains augment pi3kinase\/akt\/bcl-xl activation and cd8+ T cell\u2013mediated tumor eradication","volume":"18","author":"Zhong","year":"2010","journal-title":"Mol Ther"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aay8248","article-title":"4-1bb costimulation promotes car T cell survival through noncanonical nf-\u03bab signaling","volume":"13","author":"Philipson","year":"2020","journal-title":"Sci Signaling"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abo0777","article-title":"Antigen-specific depletion of cd4+ T cells by car T cells reveals distinct roles of higher-and lower-affinity tcrs during autoimmunity","volume":"7","author":"Yi","year":"2022","journal-title":"Sci Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2022-002907","article-title":"Car T cells for treating autoimmune diseases","volume":"9","author":"Blache","year":"2023","journal-title":"RMD Open"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-226142","article-title":"Cd19-car T-cell therapy induces deep tissue depletion of B cells","volume":"84","author":"Tur","year":"2025","journal-title":"Ann Rheumatic Dis"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e136185","DOI":"10.1172\/jci.insight.136185","article-title":"Cd19-targeted car regulatory T cells suppress B cell pathology without gvhd","volume":"5","author":"Imura","year":"2020","journal-title":"JCI Insight"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-225638","article-title":"Potential and pitfalls of repurposing the car-T cell regimen for the treatment of autoimmune disease","volume":"83","author":"Daamen","year":"2024","journal-title":"Ann Rheumatic Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.999549","article-title":"Target tumor microenvironment by innate T cells","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000413","article-title":"Clinical grade manufacture of cyad-101, a nkg2d-based, first in class, non\u2013gene-edited allogeneic car T-cell therapy","volume":"45","author":"Michaux","year":"2022","journal-title":"J Immunother"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.2043","article-title":"An exploratory clinical trial on intra-lumbar injection of B7h3-specific allogeneic universal car-T cells in patients with recurrent high-grade gliomas","author":"Shang","year":"2023","journal-title":"Am Soc Clin Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-168877","article-title":"Phase 1 dose escalation study of the rapidly switchable universal car-T therapy unicar-T-cd123 in relapsed\/refractory aml","author":"Ehninger","year":"2022","journal-title":"Am Soc Hematol Washington DC"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-169114","article-title":"Tvt car7: phase 1 clinical trial of base-edited\u201d Universal\u201d Car7 T cells for paediatric relapsed\/refractory T-all","author":"Chiesa","year":"2022","journal-title":"Am Soc Hematol Washington DC"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq3010","article-title":"Phase 1 clinical trial of crispr-engineered car19 universal T cells for treatment of children with refractory B cell leukemia","volume":"14","author":"Ottaviano","year":"2022","journal-title":"Sci Trans Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02182-7","article-title":"Allogeneic bcma-targeting car T cells in relapsed\/refractory multiple myeloma: phase 1 universal trial interim results","volume":"29","author":"Mailankody","year":"2023","journal-title":"Nat Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1182\/blood-2024-207322","article-title":"A novel generation of anti-cd7 universal car-T therapy for patients with relapsed or refractory cd7 positive T-all\/lbl: A phase I clinical trial","volume":"144","author":"Hu","year":"2024","journal-title":"Blood"},{"key":"B30","doi-asserted-by":"publisher","first-page":"4890","DOI":"10.1016\/j.cell.2024.06.027","article-title":"Allogeneic cd19-targeted car-T therapy in patients with severe myositis and systemic sclerosis","volume":"187","author":"Wang","year":"2024","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41591-025-04191-8","article-title":"Anti-cd19 car T cells for pediatric patients with treatment-refractory autoimmune diseases","author":"Becilli","year":"2026","journal-title":"Nat Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/d41591-023-00042-6","article-title":"First two patients receive car T cell therapy for hiv","volume":"29","author":"Carvalho","year":"2023","journal-title":"Nat Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s12943-025-02386-8","article-title":"Advancing car-based cell therapies for solid tumours: challenges, therapeutic strategies, and perspectives","volume":"24","author":"Azeez","year":"2025","journal-title":"Mol Cancer"},{"key":"B34","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41577-022-00732-1","article-title":"Roles of natural killer cells in immunity to cancer, and applications to immunotherapy","volume":"23","author":"Wolf","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40364-022-00364-6","article-title":"Car-nk cells for cancer immunotherapy: from bench to bedside","volume":"10","author":"Zhang","year":"2022","journal-title":"biomark Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/s13287-020-01741-4","article-title":"Genome engineering of induced pluripotent stem cells to manufacture natural killer cell therapies","volume":"11","author":"Shankar","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1675807","article-title":"Beyond car-T cells: exploring car-nk, car-M, and car-\u0393\u03b4 T strategies in solid tumor immunotherapy","volume":"16","author":"Hou","year":"2025","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/d41573-025-00134-7","article-title":"In vivo engineering broadens car-T cell therapy use","volume":"24","author":"Villanueva","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-011759","article-title":"T cell-specific non-viral DNA delivery and in vivo car-T generation using targeted lipid nanoparticles","volume":"13","author":"Bimbo","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.3390\/cells14151136","article-title":"Nanotechnology-based delivery of crispr\/cas9 for cancer treatment: A comprehensive review","volume":"14","author":"Rauf","year":"2025","journal-title":"Cells"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.07.006","article-title":"Efficient in vivo generation of car T cells using a retargeted fourth-generation lentiviral vector","volume":"33","author":"Coradin","year":"2025","journal-title":"Mol Ther"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.865424","article-title":"Sustainable clinical development of car-T cells\u2013switching from viral transduction towards crispr-cas gene editing","volume":"13","author":"Wagner","year":"2022","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.3390\/v15091801","article-title":"Innate immune response to viral vectors in gene therapy","volume":"15","author":"Wang","year":"2023","journal-title":"Viruses"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12967-025-06524-0","article-title":"Optimizing viral transduction in immune cell therapy manufacturing: key process design considerations","volume":"23","author":"Dan","year":"2025","journal-title":"J Trans Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2023.01.005","article-title":"Engineered exosome-mediated messenger rna and single-chain variable fragment delivery for human chimeric antigen receptor T-cell engineering","volume":"25","author":"Si","year":"2023","journal-title":"Cytotherapy"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002737","article-title":"Bispecific binder redirected lentiviral vector enables in vivo engineering of car-T cells","volume":"9","author":"Huckaby","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwae018","article-title":"Lymph node-biomimetic scaffold boosts car-T therapy against solid tumor","volume":"11","author":"Liao","year":"2024","journal-title":"Natl Sci Rev"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.04.040","article-title":"Biomaterial-based scaffolds for direct in situ programming of tumor-infiltrating T lymphocytes","volume":"370","author":"Inamdar","year":"2024","journal-title":"J Controlled Rel"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1465191","article-title":"Application of novel car technologies to improve treatment of autoimmune disease","volume":"15","author":"Cheever","year":"2024","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav1648","article-title":"Sustained B cell depletion by cd19-targeted car T cells is a highly effective treatment for murine lupus","volume":"11","author":"Kansal","year":"2019","journal-title":"Sci Trans Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200080","article-title":"Car-T cell\u2013mediated B-cell depletion in central nervous system autoimmunity","volume":"10","author":"Gupta","year":"2023","journal-title":"Neurol: Neuroimmunol Neuroinflamm"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201809158","article-title":"In vivo generation of human cd 19-car T cells results in B-cell depletion and signs of cytokine release syndrome","volume":"10","author":"Pfeiffer","year":"2018","journal-title":"EMBO Mol Med"},{"key":"B53","doi-asserted-by":"publisher","first-page":"100749","DOI":"10.1016\/j.medj.2025.100749","article-title":"Allogeneic cd19-targeted car-T therapy in refractory systemic lupus erythematosus achieved durable remission","volume":"6","author":"Wang","year":"2025","journal-title":"Med"},{"key":"B54","doi-asserted-by":"publisher","first-page":"4835","DOI":"10.1182\/blood-2023-186669","article-title":"Cd19\/bcma car-T cell therapy for refractory systemic lupus erythematosus-safety and preliminary efficacy data from a phase I clinical study","volume":"142","author":"Feng","year":"2023","journal-title":"Blood"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03899-x","article-title":"Allogeneic cd19-targeting T cells for treatment-refractory systemic lupus erythematosus: A phase 1 trial","volume":"31","author":"Wang","year":"2025","journal-title":"Nat Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02017-5","article-title":"Anti-cd19 car T cell therapy for refractory systemic lupus erythematosus","volume":"28","author":"Mackensen","year":"2022","journal-title":"Nat Med"},{"key":"B57","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1056\/NEJMoa2308917","article-title":"Cd19 car T-cell therapy in autoimmune disease\u2014a case series with follow-up","volume":"390","author":"M\u00fcller","year":"2024","journal-title":"New Engl J Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-025-01141-w","article-title":"Defining immune reset: achieving sustained remission in autoimmune diseases","volume":"25","author":"Junt","year":"2025","journal-title":"Nat Rev Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-694356","article-title":"Persistence of long-lived plasma cells and humoral immunity in individuals responding to cd19-directed car T-cell therapy","volume":"128","author":"Bhoj","year":"2016","journal-title":"Blood J Am Soc Hematol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03937-8","article-title":"Co-infusion of cd19-targeting and bcma-targeting car-T cells for treatment-refractory systemic lupus erythematosus: A phase 1 trial","volume":"31","author":"Feng","year":"2025","journal-title":"Nat Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-225785","article-title":"Bcma-cd19 compound car T cells for systemic lupus erythematosus: A phase 1 open-label clinical trial","volume":"83","author":"Wang","year":"2024","journal-title":"Ann Rheumatic Dis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1509956","article-title":"From promise to practice: car T and treg cell therapies in autoimmunity and other immune-mediated diseases","volume":"15","author":"Bulliard","year":"2024","journal-title":"Front Immunol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1038\/s41467-024-46448-9","article-title":"Regulatory T cells expressing cd19-targeted chimeric antigen receptor restore homeostasis in systemic lupus erythematosus","volume":"15","author":"Doglio","year":"2024","journal-title":"Nat Commun"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2025.07.678","article-title":"Differential transcriptomic profiles of A2. Car-tregs in recipients with rejecting versus accepting allogeneic heart allografts","volume":"25","author":"Jeong","year":"2025","journal-title":"Am J Transplant"},{"key":"B65","doi-asserted-by":"publisher","first-page":"103057","DOI":"10.1016\/j.jaut.2023.103057","article-title":"Supraphysiological foxp3 expression in human car-tregs results in improved stability, efficacy, and safety of car-treg products for clinical application","volume":"138","author":"Henschel","year":"2023","journal-title":"J Autoimmun"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004000","article-title":"How I prevent infections in patients receiving cd19-targeted chimeric antigen receptor T cells for B-cell Malignancies","volume":"136","author":"Hill","year":"2020","journal-title":"Blood J Am Soc Hematol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy152","article-title":"Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells","volume":"67","author":"Park","year":"2018","journal-title":"Clin Infect Dis"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000986","article-title":"Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with ddx3: implications for immune evasion","volume":"6","author":"Wang","year":"2010","journal-title":"PloS Pathog"},{"key":"B69","doi-asserted-by":"publisher","first-page":"7425","DOI":"10.3390\/ijms22147425","article-title":"Structural evaluation of the spike glycoprotein variants on sars-cov-2 transmission and immune evasion","volume":"22","author":"Salleh","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B70","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1146\/annurev.med.53.082901.104053","article-title":"Viral persistence: hiv\u2019s strategies of immune system evasion","volume":"53","author":"Johnson","year":"2002","journal-title":"Annu Rev Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00242","article-title":"A trispecific anti-hiv chimeric antigen receptor containing the ccr5 N-terminal region","volume":"10","author":"Hajduczki","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"e141502","DOI":"10.1172\/jci.insight.141502","article-title":"Stem cell\u2013derived car T cells traffic to hiv reservoirs in macaques","volume":"6","author":"Barber-Axthelm","year":"2021","journal-title":"JCI Insight"},{"key":"B73","doi-asserted-by":"publisher","first-page":"e153204","DOI":"10.1172\/JCI153204","article-title":"Hiv-specific car T cells return to the clinic","volume":"131","author":"Peterson","year":"2021","journal-title":"J Clin Invest"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e150211","DOI":"10.1172\/JCI150211","article-title":"Broadly neutralizing antibody\u2013derived car T cells reduce viral reservoir in individuals infected with hiv-1","volume":"131","author":"Liu","year":"2021","journal-title":"J Clin Invest"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.04.047","article-title":"T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice","volume":"145","author":"Krebs","year":"2013","journal-title":"Gastroenterology"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1340619","article-title":"Cars derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells","volume":"15","author":"Schreiber","year":"2024","journal-title":"Front Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.02.001","article-title":"Evaluation of a fully human, hepatitis B virus-specific chimeric antigen receptor in an immunocompetent mouse model","volume":"27","author":"Festag","year":"2019","journal-title":"Mol Ther"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.652223","article-title":"Car-nk cells effectively target sars-cov-2-spike-expressing cell lines in vitro","volume":"12","author":"Ma","year":"2021","journal-title":"Front Immunol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1421","article-title":"Targeting sars-cov-2 infection through car-T-like bispecific T cell engagers incorporating ace2","volume":"11","author":"Dogan","year":"2022","journal-title":"Clin Trans Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2022-165968","article-title":"Sars-cov-2 vaccine-induced cellular and humoral immunity in patients after cd19. Car-T cell therapy","volume":"140","author":"Reimann","year":"2022","journal-title":"Blood"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.06.004","article-title":"Ligand-induced degradation of a car permits reversible remote control of car T cell activity in vitro and in vivo","volume":"28","author":"Richman","year":"2020","journal-title":"Mol Ther"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1106152","article-title":"Inducible apoptosis as a safety switch for adoptive cell therapy","volume":"365","author":"Di Stasi","year":"2011","journal-title":"New Engl J Med"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.755639","article-title":"Inclusion of the inducible caspase 9 suicide gene in car construct increases safety of car. Cd19 T cell therapy in B-cell Malignancies","volume":"12","author":"Guercio","year":"2021","journal-title":"Front Immunol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"e007426","DOI":"10.1136\/jitc-2023-007426","article-title":"Her2 and hla-a* 02 dual car-T cells utilize loh in a not logic gate to address on-target off-tumor toxicity","volume":"11","author":"Bassan","year":"2023","journal-title":"J ImmunoTher Cancer"},{"key":"B85","doi-asserted-by":"publisher","first-page":"2848","DOI":"10.1158\/1538-7445.AM2022-2848","article-title":"Incorporation of inhibitory signaling domains into chimeric antigen receptors (Icar) designed for self-regulation of canonical car-T to treat solid tumors","volume":"82","author":"Bassan","year":"2022","journal-title":"Cancer Res"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2312374120","article-title":"Dual-inhibitory domain icars improve the efficiency of the and-not gate car T strategy","volume":"120","author":"Bangayan","year":"2023","journal-title":"Proc Natl Acad Sci"},{"key":"B87","doi-asserted-by":"publisher","first-page":"215ra172","DOI":"10.1126\/scitranslmed.3006597","article-title":"Pd-1\u2013and ctla-4\u2013based inhibitory chimeric antigen receptors (Icars) divert off-target immunotherapy responses","volume":"5","author":"Fedorov","year":"2013","journal-title":"Sci Trans Med"},{"key":"B88","first-page":"3184","article-title":"Dual-switch car-T cells: orthogonal molecular switches to control activation and elimination of car-T cells to target cd123+ Cancer","volume":"130","author":"Bayle","year":"2017","journal-title":"Blood"},{"key":"B89","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/s41571-019-0258-5","article-title":"Tki-based on\/off switch for car T cells","volume":"16","author":"Killock","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1911154117","article-title":"A conformation-specific on-switch for controlling car T cells with an orally available drug","volume":"117","author":"Zajc","year":"2020","journal-title":"Proc Natl Acad Sci"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.PEDIATRIC24-PR010","article-title":"Abstract pr010: developing a safe and potent tumor-targeting gated car-T cell therapy for dipg: A deadly pediatric brain tumor","volume":"84","author":"Venkataraman","year":"2024","journal-title":"Cancer Res"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-023-00828-w","article-title":"Car T cell design: approaching the elusive and-gate","volume":"33","author":"Zhao","year":"2023","journal-title":"Cell Res"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0101","article-title":"Programming car T cell tumor recognition: tuned antigen sensing and logic gating","volume":"13","author":"Hamieh","year":"2023","journal-title":"Cancer Discov"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.744823","article-title":"Advances in universal car-T cell therapy","volume":"12","author":"Lin","year":"2021","journal-title":"Front Immunol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13045-018-0677-2","article-title":"Universal cars, universal T cells, and universal car T cells","volume":"11","author":"Zhao","year":"2018","journal-title":"J Hematol Oncol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1016\/j.stem.2025.05.007","article-title":"Preferential tumor targeting of her2 by ipsc-derived car T cells engineered to overcome multiple barriers to solid tumor efficacy","volume":"32","author":"Hosking","year":"2025","journal-title":"Cell Stem Cell"},{"key":"B97","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1182\/blood-2024-208634","article-title":"Generation of functional ipsc-derived car-T cells for cancer immunotherapy via G9a\/glp inhibition","volume":"144","author":"Jing","year":"2024","journal-title":"Blood"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.07.046","article-title":"Glycan shielding enables tcr-sufficient allogeneic car-T therapy","volume":"188","author":"Wu","year":"2025","journal-title":"Cell"},{"key":"B99","doi-asserted-by":"publisher","first-page":"101250","DOI":"10.1016\/j.omtm.2024.101250","article-title":"Car-T cell manufacturing landscape\u2014Lessons from the past decade and considerations for early clinical development","volume":"32","author":"Dias","year":"2024","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02444-y","article-title":"Leveraging crispr gene editing technology to optimize the efficacy, safety and accessibility of car T-cell therapy","volume":"38","author":"Lei","year":"2024","journal-title":"Leukemia"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024024491","article-title":"Putting together the pieces: car into cd3\u03b6 Locus","volume":"143","author":"Casucci","year":"2024","journal-title":"Blood"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09507-9","article-title":"Systematic discovery of crispr-boosted car T cell immunotherapies","volume":"646","author":"Datlinger","year":"2025","journal-title":"Nature"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1067","article-title":"Programming gene and engineered-cell therapies with synthetic biology","volume":"359","author":"Kitada","year":"2018","journal-title":"Science"},{"key":"B104","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.copbio.2018.08.008","article-title":"Engineering mammalian cells for disease diagnosis and treatment","volume":"55","author":"Teixeira","year":"2019","journal-title":"Curr Opin Biotechnol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade0156","article-title":"Multidimensional control of therapeutic human cell function with synthetic gene circuits","volume":"378","author":"Li","year":"2022","journal-title":"Science"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-23-0240","article-title":"Advancing car T-cell therapies with artificial intelligence: opportunities and challenges","volume":"6","author":"Luciani","year":"2025","journal-title":"Blood Cancer Discov"},{"key":"B107","doi-asserted-by":"publisher","first-page":"e005360","DOI":"10.1136\/jitc-2022-005360","article-title":"Computational model of car T-cell immunotherapy dissects and predicts leukemia patient responses at remission, resistance, and relapse","volume":"10","author":"Liu","year":"2022","journal-title":"J ImmunoTher Cancer"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq0225","article-title":"Decoding car T cell phenotype using combinatorial signaling motif libraries and machine learning","volume":"378","author":"Daniels","year":"2022","journal-title":"Science"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0297-y","article-title":"Engineering strategies to overcome the current roadblocks in car T cell therapy","volume":"17","author":"Rafiq","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41522-025-00882-9","article-title":"Crispr-engineered microbiome: living therapeutics revolutionize blood cancer immunotherapy","volume":"12","author":"Cheng","year":"2025","journal-title":"NPJ Biofilms Microb"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1226518","article-title":"Engineering nk-car. 19 cells with the il-15\/il-15r\u03b1 Complex improved proliferation and anti-tumor effect in vivo","volume":"14","author":"Silvestre","year":"2023","journal-title":"Front Immunol"},{"key":"B112","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/cells15010021","article-title":"Car-nk engineering to overcome tme barriers","volume":"15","author":"Islam","year":"2025","journal-title":"Cells"},{"key":"B113","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","article-title":"Car-T cell therapy: current limitations and potential strategies","volume":"11","author":"Sterner","year":"2021","journal-title":"Blood Cancer J"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201607485","article-title":"Clinical development of car T cells\u2014Challenges and opportunities in translating innovative treatment concepts","volume":"9","author":"Hartmann","year":"2017","journal-title":"EMBO Mol Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1802718\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:17:23Z","timestamp":1774369043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1802718\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":114,"alternative-id":["10.3389\/fimmu.2026.1802718"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1802718","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"article-number":"1802718"}}