{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T04:27:11Z","timestamp":1792902431943,"version":"4.5.0"},"reference-count":165,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"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                    Chimeric Antigen Receptor (CAR)-T cell therapy represents a transformative breakthrough in cancer immunotherapy by harnessing the adaptive immune system to selectively eradicate cancer cells. Pioneering advances in the treatment of hematological malignancies have led to the FDA approval of several CAR-T cell therapies, particularly for patients with relapsed or refractory disease. This success is a result of continuous refinements in CAR architecture, which have evolved from early prototypes with limited therapeutic efficacy to advanced next-generation receptors that incorporate co-stimulatory domains, cytokine signaling, safety switches, and precision control mechanisms. This review elucidates the fundamental rationale behind CAR-T cell development and addresses key biological challenges encountered. Advances in receptor engineering, metabolic reprogramming, and optimized immune signaling have markedly enhanced the persistence, antitumor activity, and safety profiles of CAR-T cells. Additionally, emerging genetic engineering tools, including CRISPR, base editing, prime editing, and RNA and epigenome editing, hold promise for reducing immunogenicity and minimizing the risk of graft-versus-host disease (GVHD). However, CAR-T cell therapy continues to face several challenges, including severe side effects such as cytokine release syndrome (CRS) and neurotoxicity, inconsistent therapeutic responses, and high production costs. To overcome these barriers, novel approaches are under development that include generating CAR-T cells\n                    <jats:italic>in vivo<\/jats:italic>\n                    , utilizing logic-gated CAR systems, and expanding CAR platforms to include other immune effector cells, such as natural killer cells (CAR-NK) and macrophages (CAR-M). The future of CAR-based therapies is expected to integrate synthetic biology, immune checkpoint modulation, and innovative delivery methods to enhance both therapeutic efficacy and safety. This review synthesizes current knowledge and emerging strategies to guide future advancements aimed at expanding the applicability of CAR therapy to various cancer types and potentially other diseases.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1615212","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T04:10:25Z","timestamp":1752725425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":43,"title":["Tracing the development of CAR-T cell design: from concept to next-generation platforms"],"prefix":"10.3389","volume":"16","author":[{"given":"Ahdab A.","family":"Alsaieedi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kawther A.","family":"Zaher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.5938","article-title":"Immunotherapy - strategies for expanding its role in the treatment of all major tumor sites","volume":"11","author":"Sanghera","year":"2019","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0548","article-title":"The basic principles of chimeric antigen receptor design","volume":"3","author":"Sadelain","year":"2013","journal-title":"Cancer Discov"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41577-021-00547-6","article-title":"Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy","volume":"22","author":"Morris","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B6","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":"B7","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":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0042-2","article-title":"CAR T cells for infection, autoimmunity and allotransplantation","volume":"18","author":"Maldini","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188049","article-title":"From bench to bedside: the history and progress of CAR T cell therapy","volume":"14","author":"Mitra","year":"2023","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(87)90502-X","article-title":"Expression of chimeric receptor composed of immunoglobulin-derived V regions and T-cell receptor-derived C regions","volume":"149","author":"Kuwana","year":"1987","journal-title":"Biochem Biophys Res Commun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.720","article-title":"Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors","volume":"90","author":"Eshhar","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.24.10024","article-title":"Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity","volume":"86","author":"Gross","year":"1989","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1183","article-title":"A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer","volume":"12","author":"Kershaw","year":"2006","journal-title":"Clin Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.01.021","article-title":"Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells","volume":"44","author":"Kawalekar","year":"2016","journal-title":"Immunity"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.6.2791","article-title":"Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product","volume":"161","author":"Finney","year":"1998","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"95ra73","DOI":"10.1126\/scitranslmed.3002842","article-title":"T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia","volume":"3","author":"Kalos","year":"2011","journal-title":"Sci Transl Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103849","article-title":"Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia","volume":"365","author":"Porter","year":"2011","journal-title":"N Engl J Med"},{"key":"B18","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":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024850","article-title":"Idecabtagene vicleucel in relapsed and refractory multiple myeloma","volume":"384","author":"Munshi","year":"2021","journal-title":"N Engl J Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.10.4318","article-title":"Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells","volume":"91","author":"Moritz","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B21","article-title":"In vivo antitumor activity of T cells redirected with chimeric antibody\/T-cell receptor genes","volume":"55","author":"Hwu","year":"1995","journal-title":"Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0102-70","article-title":"Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta\/CD28 receptor","volume":"20","author":"Maher","year":"2002","journal-title":"Nat Biotechnol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"177ra38","DOI":"10.1126\/scitranslmed.3005930","article-title":"CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia","volume":"5","author":"Brentjens","year":"2013","journal-title":"Sci Transl Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.04.020","article-title":"CD28 costimulation: from mechanism to therapy","volume":"44","author":"Esensten","year":"2016","journal-title":"Immunity"},{"key":"B25","doi-asserted-by":"publisher","first-page":"7296","DOI":"10.1038\/s41467-021-27613-w","article-title":"CD137 (4-1BB) costimulation of CD8(+) T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation","volume":"12","author":"Otano","year":"2021","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403302","article-title":"Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia","volume":"18","author":"Imai","year":"2004","journal-title":"Leukemia"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.09.004","article-title":"Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells","volume":"28","author":"Zhao","year":"2015","journal-title":"Cancer Cell"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3838","article-title":"4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors","volume":"21","author":"Long","year":"2015","journal-title":"Nat Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-04-348540","article-title":"Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias","volume":"118","author":"Brentjens","year":"2011","journal-title":"Blood"},{"key":"B30","doi-asserted-by":"publisher","first-page":"303ra139","DOI":"10.1126\/scitranslmed.aac5415","article-title":"Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia","volume":"7","author":"Porter","year":"2015","journal-title":"Sci Transl Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma","volume":"380","author":"Schuster","year":"2019","journal-title":"N Engl J Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2016.10.020","article-title":"Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma","volume":"25","author":"Locke","year":"2017","journal-title":"Mol Ther"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2116133","article-title":"Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma","volume":"386","author":"Locke","year":"2022","journal-title":"N Engl J Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2114254","DOI":"10.1080\/21645515.2022.2114254","article-title":"Current updates on generations, approvals, and clinical trials of CAR T-cell therapy","volume":"18","author":"Asmamaw Dejenie","year":"2022","journal-title":"Hum Vaccin Immunother"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.09.009","article-title":"In vivo fate and activity of second- versus third-generation CD19-specific CAR-T cells in B cell non-Hodgkin\u2019s lymphomas","volume":"26","author":"Ramos","year":"2018","journal-title":"Mol Ther"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003351","article-title":"Epitope spreading driven by the joint action of CART cells and pharmacological STING stimulation counteracts tumor escape via antigen-loss variants","volume":"9","author":"Conde","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0426","article-title":"A phase I\/IIa trial using CD19-targeted third-generation CAR T cells for lymphoma and leukemia","volume":"24","author":"Enblad","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-125423","article-title":"Third-generation CAR T cells targeting CD19 are associated with an excellent safety profile and might improve persistence of CAR T cells in treated patients","volume":"134","author":"Schubert","year":"2019","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-024-00275-6","article-title":"HER2-targeting CAR-T cells show highly efficient anti-tumor activity against glioblastoma both in vitro and in vivo","volume":"25","author":"Li","year":"2024","journal-title":"Genes Immun"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2015.1046430","article-title":"TRUCKs: the fourth generation of CARs","volume":"15","author":"Chmielewski","year":"2015","journal-title":"Expert Opin Biol Ther"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1090959","DOI":"10.3389\/fimmu.2022.1090959","article-title":"CAR T cell therapy becomes CHIC: \u201ccytokine help intensified CAR\u201d T cells","volume":"13","author":"Thomas","year":"2022","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/acg2.84","article-title":"TRUCKS, the fourth-generation CAR T cells: Current developments and clinical translation","volume":"3","author":"Chmielewski","year":"2020","journal-title":"Adv In Cell And Gene Ther"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123586","article-title":"Immunomodulatory effects of IL-2 and IL-15; implications for cancer immunotherapy","volume":"12","author":"Yang","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.728962","article-title":"CD19 CAR-T cells with membrane-bound IL-15 for B-cell acute lymphoblastic leukemia after failure of CD19 and CD22 CAR-T cells: case report","volume":"12","author":"Sun","year":"2021","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005187","article-title":"GD2-targeting CAR-T cells enhanced by transgenic IL-15 expression are an effective and clinically feasible therapy for glioblastoma","volume":"10","author":"Gargett","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1811","article-title":"Eradication of neuroblastoma by T cells redirected with an optimized GD2-specific chimeric antigen receptor and interleukin-15","volume":"25","author":"Chen","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003897","article-title":"Targeting disialoganglioside GD2 with chimeric antigen receptor-redirected T cells in lung cancer","volume":"10","author":"Reppel","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08261-8","article-title":"Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers","volume":"637","author":"Steffin","year":"2025","journal-title":"Nature"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.09.021","article-title":"Arming CAR-T cells with cytokines and more: Innovations in the fourth-generation CAR-T development","volume":"31","author":"Tang","year":"2023","journal-title":"Mol Ther"},{"key":"B50","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/s41467-021-21241-0","article-title":"Targeting IL-21 to tumor-reactive T cells enhances memory T cell responses and anti-PD-1 antibody therapy","volume":"12","author":"Li","year":"2021","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1016","article-title":"Interleukin-7 mediates selective expansion of tumor-redirected cytotoxic T lymphocytes (CTLs) without enhancement of regulatory T-cell inhibition","volume":"20","author":"Perna","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0293","article-title":"Glypican-3-specific CAR T cells coexpressing IL15 and IL21 have superior expansion and antitumor activity against hepatocellular carcinoma","volume":"8","author":"Batra","year":"2020","journal-title":"Cancer Immunol Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.09.015","article-title":"CAR T cell therapy for solid tumors: bright future or dark reality","volume":"28","author":"Wagner","year":"2020","journal-title":"Mol Ther"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4086","article-title":"IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor","volume":"36","author":"Adachi","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58814","article-title":"IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors","volume":"121","author":"Kerkar","year":"2011","journal-title":"J Clin Invest"},{"key":"B56","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.omto.2022.03.009","article-title":"CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities","volume":"25","author":"Kankeu Fonkoua","year":"2022","journal-title":"Mol Ther Oncolytics"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1542917","DOI":"10.1080\/2162402X.2018.1542917","article-title":"Safety and efficacy of Tet-regulated IL-12 expression in cancer-specific T cells","volume":"8","author":"Alsaieedi","year":"2019","journal-title":"Oncoimmunology"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.002","article-title":"Augmentation of antitumor immunity by human and mouse CAR T cells secreting IL-18","volume":"20","author":"Hu","year":"2017","journal-title":"Cell Rep"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0874-1","article-title":"Cytokine IL-36gamma improves CAR T-cell functionality and induces endogenous antitumor response","volume":"35","author":"Li","year":"2021","journal-title":"Leukemia"},{"key":"B60","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12943-025-02334-6","article-title":"Strategies to overcome tumour relapse caused by antigen escape after CAR T therapy","volume":"24","author":"Lu","year":"2025","journal-title":"Mol Cancer"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0676-7","article-title":"Adoptive cellular therapy with T cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity","volume":"21","author":"Lai","year":"2020","journal-title":"Nat Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4478","article-title":"A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects","volume":"24","author":"Kagoya","year":"2018","journal-title":"Nat Med"},{"key":"B63","doi-asserted-by":"publisher","first-page":"102931","DOI":"10.1016\/j.ebiom.2020.102931","article-title":"CAR-T design: Elements and their synergistic function","volume":"58","author":"Jayaraman","year":"2020","journal-title":"EBioMedicine"},{"key":"B64","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s00018-021-04089-x","article-title":"Tuning the ignition of CAR: optimizing the affinity of scFv to improve CAR-T therapy","volume":"79","author":"Duan","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.12.7647","article-title":"T cell activation by antibody-like immunoreceptors: increase in affinity of the single-chain fragment domain above threshold does not increase T cell activation against antigen-positive target cells but decreases selectivity","volume":"173","author":"Chmielewski","year":"2004","journal-title":"J Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1920662117","article-title":"Structure-guided engineering of the affinity and specificity of CARs against Tn-glycopeptides","volume":"117","author":"Sharma","year":"2020","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.04.024","article-title":"A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization","volume":"25","author":"Drent","year":"2017","journal-title":"Mol Ther"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1182409","article-title":"Screening and characterization of the scFv for chimeric antigen receptor T cells targeting CEA-positive carcinoma","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0916","article-title":"Treatment with humanized selective CD19CAR-T cells shows efficacy in highly treated B-ALL patients who have relapsed after receiving murine-based CD19CAR-T therapies","volume":"25","author":"Zhao","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1339","article-title":"Sustained therapeutic efficacy of humanized anti-CD19 chimeric antigen receptor T cells in relapsed\/refractory acute lymphoblastic leukemia","volume":"26","author":"Heng","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0945","article-title":"Tuning the antigen density requirement for CAR T-cell activity","volume":"10","author":"Majzner","year":"2020","journal-title":"Cancer Discov"},{"key":"B72","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s40364-022-00417-w","article-title":"CAR-T cell potency: from structural elements to vector backbone components","volume":"10","author":"Mazinani","year":"2022","journal-title":"biomark Res"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.07.013","article-title":"Function of novel anti-CD19 chimeric antigen receptors with human variable regions is affected by hinge and transmembrane domains","volume":"25","author":"Alabanza","year":"2017","journal-title":"Mol Ther"},{"key":"B74","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13045-025-01672-8","article-title":"Correction: Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells","volume":"18","author":"Qin","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0421-7","article-title":"A safe and potent anti-CD19 CAR T cell therapy","volume":"25","author":"Ying","year":"2019","journal-title":"Nat Med"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1097\/01.cji.0000161397.96582.59","article-title":"The role of extracellular spacer regions in the optimal design of chimeric immune receptors: evaluation of four different scFvs and antigens","volume":"28","author":"Guest","year":"2005","journal-title":"J Immunother"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.10.7028","article-title":"Antigen sensitivity of CD22-specific chimeric TCR is modulated by target epitope distance from the cell membrane","volume":"180","author":"James","year":"2008","journal-title":"J Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.12.009","article-title":"Engineering and design of chimeric antigen receptors","volume":"12","author":"Guedan","year":"2019","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.91","article-title":"Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc \u2018spacer\u2019 domain in the extracellular moiety of chimeric antigen receptors avoids \u2018off-target\u2019 activation and unintended initiation of an innate immune response","volume":"17","author":"Hombach","year":"2010","journal-title":"Gene Ther"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-14-0127","article-title":"The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity","volume":"3","author":"Hudecek","year":"2015","journal-title":"Cancer Immunol Res"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.208","article-title":"Chimeric antigen receptors with mutated IgG4 Fc spacer avoid fc receptor binding and improve T cell persistence and antitumor efficacy","volume":"23","author":"Jonnalagadda","year":"2015","journal-title":"Mol Ther"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00507","article-title":"Extracellular NGFR spacers allow efficient tracking and enrichment of fully functional CAR-T cells co-expressing a suicide gene","volume":"9","author":"Casucci","year":"2018","journal-title":"Front Immunol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051182","article-title":"Hinge and transmembrane domains of chimeric antigen receptor regulate receptor expression and signaling threshold","volume":"9","author":"Fujiwara","year":"2020","journal-title":"Cells"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.09.019","article-title":"Genetic modification of T cells","volume":"17","author":"Bonini","year":"2011","journal-title":"Biol Blood Marrow Transpl"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-545020","article-title":"A highly compact epitope-based marker\/suicide gene for easier and safer T-cell therapy","volume":"124","author":"Philip","year":"2014","journal-title":"Blood"},{"key":"B86","doi-asserted-by":"publisher","first-page":"aab4077","DOI":"10.1126\/science.aab4077","article-title":"Remote control of therapeutic T cells through a small molecule-gated chimeric receptor","volume":"350","author":"Wu","year":"2015","journal-title":"Science"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124430","article-title":"Sensitive and adaptable pharmacological control of CAR T cells through extracellular receptor dimerization","volume":"5","author":"Leung","year":"2019","journal-title":"JCI Insight"},{"key":"B88","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 U.S.A"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2021.07.002","article-title":"Safety switches for adoptive cell therapy","volume":"74","author":"Sahillioglu","year":"2022","journal-title":"Curr\u00a0Opin Immunol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1016\/j.ymthe.2020.07.010","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":"B91","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s12896-019-0537-3","article-title":"Modulation of chimeric antigen receptor surface expression by a small molecule switch","volume":"19","author":"Juillerat","year":"2019","journal-title":"BMC Biotechnol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-023-01646-6","article-title":"In situ PEGylation of CAR T cells alleviates cytokine release syndrome and neurotoxicity","volume":"22","author":"Gong","year":"2023","journal-title":"Nat\u00a0Mater"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay9209","article-title":"Engineering light-controllable CAR T cells for cancer immunotherapy","volume":"6","author":"Huang","year":"2020","journal-title":"Sci Adv"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00779-w","article-title":"Control of the activity of CAR-T cells within tumours via focused ultrasound","volume":"5","author":"Wu","year":"2021","journal-title":"Nat BioMed Eng"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X20666220201092908","article-title":"Potential goals, challenges, and safety of focused ultrasound application for central nervous system disorders","volume":"20","author":"Perez-Neri","year":"2022","journal-title":"Curr Neuropharmacol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2024.e00352","article-title":"Current clinical investigations of focused ultrasound blood-brain barrier disruption: A review","volume":"21","author":"Durham","year":"2024","journal-title":"Neurotherapeutics"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-004185","article-title":"To go or not to go? Biological logic gating engineered T cells","volume":"10","author":"Abbott","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2459","article-title":"Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells","volume":"31","author":"Kloss","year":"2013","journal-title":"Nat Biotechnol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9689-9","article-title":"Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling","volume":"32","author":"Wilkie","year":"2012","journal-title":"J Clin Immunol"},{"key":"B100","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1158\/2326-6066.CIR-13-0008","article-title":"Chimeric antigen receptor T Cells with dissociated signaling domains exhibit focused antitumor activity with reduced potential for toxicity in vivo","volume":"1","author":"Lanitis","year":"2013","journal-title":"Cancer Immunol Res"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-20-0118","article-title":"Treatment of multiple myeloma using chimeric antigen receptor T cells with dual specificity","volume":"8","author":"Globerson Levin","year":"2020","journal-title":"Cancer Immunol Res"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc1855","article-title":"T cell circuits that sense antigen density with an ultrasensitive threshold","volume":"371","author":"Hernandez-Lopez","year":"2021","journal-title":"Science"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08366-0","article-title":"Engineered receptors for soluble cellular communication and disease sensing","volume":"638","author":"Piraner","year":"2025","journal-title":"Nature"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-143474","article-title":"Tandem CD19\/CD22 dual targets CAR-T cells therapy acquires superior CR rate than CD19 CAR-T cells: A case controlled study","volume":"136","author":"Cui","year":"2020","journal-title":"Blood"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87366","article-title":"Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies","volume":"126","author":"Ruella","year":"2016","journal-title":"J Clin Invest"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.185","article-title":"Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma","volume":"21","author":"Hegde","year":"2013","journal-title":"Mol Ther"},{"key":"B107","doi-asserted-by":"publisher","first-page":"215ra172","DOI":"10.1126\/scitranslmed.3006597","article-title":"PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses","volume":"5","author":"Fedorov","year":"2013","journal-title":"Sci\u00a0Transl Med"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-20-0208","article-title":"NOT-gated CD93 CAR T cells effectively target AML with minimized endothelial cross-reactivity","volume":"2","author":"Richards","year":"2021","journal-title":"Blood Cancer Discov"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12092612","article-title":"CD19-CAR-T cells bearing a KIR\/PD-1-based inhibitory CAR eradicate CD19(+)HLA-C1(-) Malignant B cells while sparing CD19(+)HLA-C1(+) healthy B cells","volume":"12","author":"Tao","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B110","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/s41467-021-21078-7","article-title":"Engineering advanced logic and distributed computing in human CAR immune cells","volume":"12","author":"Cho","year":"2021","journal-title":"Nat Commun"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252212201","article-title":"Significant advancements and evolutions in chimeric antigen receptor design","volume":"25","author":"Gaimari","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B112","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/j.cell.2018.03.038","article-title":"Universal chimeric antigen receptors for multiplexed and logical control of T cell responses","volume":"173","author":"Cho","year":"2018","journal-title":"Cell"},{"key":"B113","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1158\/2326-6066.CIR-21-0095","article-title":"CRASH-IT switch enables reversible and dose-dependent control of TCR and CAR T-cell function","volume":"9","author":"Sahillioglu","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.07.005","article-title":"Engineering CAR-T cells for next-generation cancer therapy","volume":"38","author":"Hong","year":"2020","journal-title":"Cancer Cell"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba6527","article-title":"Designed protein logic to target cells with precise combinations of surface antigens","volume":"369","author":"Lajoie","year":"2020","journal-title":"Science"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.780399","article-title":"Implementing logic gates for safer immunotherapy of cancer","volume":"12","author":"Savanur","year":"2021","journal-title":"Front Immunol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abe7378","article-title":"SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma","volume":"13","author":"Choe","year":"2021","journal-title":"Sci Transl Med"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2023.128","article-title":"Genome editing in engineered T cells for cancer immunotherapy","volume":"34","author":"Bonini","year":"2023","journal-title":"Hum Gene Ther"},{"key":"B119","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":"B120","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-405365","article-title":"A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR","volume":"119","author":"Torikai","year":"2012","journal-title":"Blood"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1038\/nature21405","article-title":"Targeting a CAR to the TRAC locus with CRISPR\/Cas9 enhances tumour rejection","volume":"543","author":"Eyquem","year":"2017","journal-title":"Nature"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23063207","article-title":"Simultaneous genetic ablation of PD-1, LAG-3, and TIM-3 in CD8 T cells delays tumor growth and improves survival outcome","volume":"23","author":"Ciraolo","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.07.021","article-title":"Current status and challenges of DNA base editing tools","volume":"28","author":"Jeong","year":"2020","journal-title":"Mol Ther"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0084-6","article-title":"Base editing: advances and therapeutic opportunities","volume":"19","author":"Porto","year":"2020","journal-title":"Nat Rev Drug Discov"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2023.03.004","article-title":"Prime editing: advances and therapeutic applications","volume":"41","author":"Zhao","year":"2023","journal-title":"Trends Biotechnol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1038\/nature17946","article-title":"Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage","volume":"533","author":"Komor","year":"2016","journal-title":"Nature"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002071","article-title":"In the business of base editors: Evolution from bench to bedside","volume":"21","author":"Porto","year":"2023","journal-title":"PloS Biol"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01595-6","article-title":"Programmable A-to-Y base editing by fusing an adenine base editor with an N-methylpurine DNA glycosylase","volume":"41","author":"Tong","year":"2023","journal-title":"Nat Biotechnol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-replace genome editing without double-strand breaks or donor DNA","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.05.014","article-title":"Prevalence of anti-adeno-associated virus immune responses in international cohorts of healthy donors","volume":"14","author":"Kruzik","year":"2019","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B131","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":"B132","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abh0272","article-title":"Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity","volume":"13","author":"Prinzing","year":"2021","journal-title":"Sci Transl Med"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-1319","article-title":"Disruption of SUV39H1-mediated H3K9 methylation sustains CAR T-cell function","volume":"14","author":"Jain","year":"2024","journal-title":"Cancer Discov"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012714","article-title":"Genetic ablation of PRDM1 in antitumor T cells enhances therapeutic efficacy of adoptive immunotherapy","volume":"139","author":"Yoshikawa","year":"2022","journal-title":"Blood"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c10631","article-title":"Robust, Durable Gene Activation In Vivo via mRNA-Encoded Activators","volume":"16","author":"Beyersdorf","year":"2022","journal-title":"ACS Nano"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.4976","article-title":"CRISPR\/dCas9-tet1-mediated DNA methylation editing","volume":"14","author":"Qian","year":"2024","journal-title":"Bio Protoc"},{"key":"B137","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1016\/j.cell.2021.03.025","article-title":"Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing","volume":"184","author":"Nunez","year":"2021","journal-title":"Cell"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.3390\/genes8010041","article-title":"RNA editing, ADAR1, and the innate immune response","volume":"8","author":"Wang","year":"2017","journal-title":"Genes (Basel)"},{"key":"B139","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.tcb.2024.06.006","article-title":"ADAR1: from basic mechanisms to inhibitors","volume":"35","author":"Rehwinkel","year":"2025","journal-title":"Trends Cell Biol"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0768-9","article-title":"Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade","volume":"565","author":"Ishizuka","year":"2019","journal-title":"Nature"},{"key":"B141","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12964-021-00716-z","article-title":"Developing PspCas13b-based enhanced RESCUE system, eRESCUE, with efficient RNA base editing","volume":"19","author":"Li","year":"2021","journal-title":"Cell Commun Signal"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-023-01531-y","article-title":"Programmable RNA base editing via targeted modifications","volume":"20","author":"Song","year":"2024","journal-title":"Nat Chem Biol"},{"key":"B143","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/j.cell.2024.01.035","article-title":"A versatile CRISPR-Cas13d platform for multiplexed transcriptomic regulation and metabolic engineering in primary human T cells","volume":"187","author":"Tieu","year":"2024","journal-title":"Cell"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2017.57","article-title":"In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers","volume":"12","author":"Smith","year":"2017","journal-title":"Nat Nanotechnol"},{"key":"B145","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201809158","article-title":"In vivo generation of human CD19-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":"B146","doi-asserted-by":"publisher","first-page":"105266","DOI":"10.1016\/j.ebiom.2024.105266","article-title":"Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment","volume":"106","author":"Bui","year":"2024","journal-title":"EBioMedicine"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.03.004","article-title":"Direct in vivo CAR T cell engineering","volume":"45","author":"Short","year":"2024","journal-title":"Trends Pharmacol Sci"},{"key":"B148","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.jconrel.2022.08.033","article-title":"Lipid nanoparticles produce chimeric antigen receptor T cells with interleukin-6 knockdown in vivo","volume":"350","author":"Zhou","year":"2022","journal-title":"J Control Release"},{"key":"B149","doi-asserted-by":"publisher","first-page":"121339","DOI":"10.1016\/j.biomaterials.2021.121339","article-title":"In situ T-cell transfection by anti-CD3-conjugated lipid nanoparticles leads to T-cell activation, migration, and phenotypic shift","volume":"281","author":"Kheirolomoom","year":"2022","journal-title":"Biomaterials"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines12101148","article-title":"Recent advances in lipid nanoparticles and their safety concerns for mRNA delivery","volume":"12","author":"Wang","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14092339","article-title":"Regulation of NKG2D stress ligands and its relevance in cancer progression","volume":"14","author":"Jones","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00349","article-title":"Adaptations of natural killer cells to self-MHC class I","volume":"5","author":"Bessoles","year":"2014","journal-title":"Front Immunol"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01145-x","article-title":"Development of NK cell-based cancer immunotherapies through receptor engineering","volume":"21","author":"Page","year":"2024","journal-title":"Cell Mol Immunol"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14153839","article-title":"CAR-NK cells: A chimeric hope or a promising therapy","volume":"14","author":"Sabbah","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.226","article-title":"Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity","volume":"32","author":"Liu","year":"2018","journal-title":"Leukemia"},{"key":"B156","doi-asserted-by":"publisher","first-page":"102975","DOI":"10.1016\/j.ebiom.2020.102975","article-title":"CAR-NK cells: A promising cellular immunotherapy for cancer","volume":"59","author":"Xie","year":"2020","journal-title":"EBioMedicine"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2022.10.011","article-title":"Gene-edited and CAR-NK cells: Opportunities and challenges with engineering of NK cells for immunotherapy","volume":"27","author":"Wu","year":"2022","journal-title":"Mol Ther Oncolytics"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0462-y","article-title":"Human chimeric antigen receptor macrophages for cancer immunotherapy","volume":"38","author":"Klichinsky","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01687-8","article-title":"A second-generation M1-polarized CAR macrophage with antitumor efficacy","volume":"25","author":"Lei","year":"2024","journal-title":"Nat Immunol"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1464218","article-title":"CAR-macrophage: Breaking new ground in cellular immunotherapy","volume":"12","author":"Huang","year":"2024","journal-title":"Front Cell Dev Biol"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1532833","article-title":"CAR-macrophages: tailoring cancer immunotherapy","volume":"15","author":"Chettri","year":"2024","journal-title":"Front Immunol"},{"key":"B162","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s13045-020-00983-2","article-title":"Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions","volume":"13","author":"Zhang","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-SITC2024.1144","article-title":"1144 Combined CAR-M and T cell therapy to remodel TGFbeta-rich solid tumors","volume":"12","author":"Sugimura","year":"2024","journal-title":"J ImmunoTher Cancer"},{"key":"B164","article-title":"FDA grants accelerated Available online at: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma. approval to lifileucel for unresectable or metastatic melanoma2024\u201321 June 2025","year":""},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202501095","article-title":"From multi-omics to visualization and beyond: bridging micro and macro insights in CAR-T cell therapy","volume":"12","author":"Gong","year":"2025","journal-title":"Adv Sci (Weinh)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1615212\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T13:11:59Z","timestamp":1753276319000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1615212\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":165,"alternative-id":["10.3389\/fimmu.2025.1615212"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1615212","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]},"article-number":"1615212"}}