{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:14:08Z","timestamp":1791886448082,"version":"4.3.4"},"reference-count":129,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Over the last decade, the emergence of several novel therapeutic approaches has changed the therapeutic perspective of human malignancies. Adoptive immunotherapy through chimeric antigen receptor T cell (CAR\u2010T), which includes the engineering of T cells to recognize tumor\u2010specific membrane antigens and, as a result, death of cancer cells, has created various clinical benefits for the treatment of several human malignancies. In particular, CAR\u2010T\u2010cell\u2010based immunotherapy is known as a critical approach for the treatment of patients with hematological malignancies such as acute lymphoblastic leukemia (ALL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and non\u2010Hodgkin's lymphoma (NHL). However, CAR\u2010T\u2010cell therapy of hematological malignancies is associated with various side effects. There are still extensive challenges in association with further progress of this therapeutic approach, from manufacturing and engineering issues to limitations of applications and serious toxicities. Therefore, further studies are required to enhance efficacy and minimize adverse events. In the current review, we summarize the development of CAR\u2010T\u2010cell\u2010based immunotherapy and current clinical antitumor applications to treat hematological malignancies. Furthermore, we will mention the current advantages, disadvantages, challenges, and therapeutic limitations of CAR\u2010T\u2010cell therapy.<\/jats:p>","DOI":"10.1002\/cam4.5551","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T06:52:03Z","timestamp":1672383123000},"page":"7844-7858","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Chimeric antigen receptor T (\n                    <scp>CAR\u2010T<\/scp>\n                    ) cells: Novel cell therapy for hematological malignancies"],"prefix":"10.1002","volume":"12","author":[{"given":"Samane","family":"Abbasi","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Sciences University of Guilan  Rasht Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milad Asghari","family":"Totmaj","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Faculty of Medicine The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoumeh","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Malekan Branch Islamic Azad University  Malekan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saba","family":"Hajazimian","sequence":"additional","affiliation":[{"name":"Immunology Research Center Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pouya","family":"Goleij","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Biology Sana Institute of Higher Education  Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Behroozi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Biotechnology, School of Medicine AJA University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behrouz","family":"Shademan","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Ege University  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-1177","authenticated-orcid":false,"given":"Alireza","family":"Isazadeh","sequence":"additional","affiliation":[{"name":"Immunology Research Center Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8642-6795","authenticated-orcid":false,"given":"Behzad","family":"Baradaran","sequence":"additional","affiliation":[{"name":"Immunology Research Center Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23916"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197148"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.152919"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.153241"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12020194"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29905"},{"issue":"9","key":"e_1_2_13_8_1","first-page":"1243","article-title":"Current management and emerging treatment strategies for multiple myeloma","volume":"60","author":"Lei M","year":"2019","journal-title":"Rinsho Ketsueki"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.254"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-017-0373-2"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000188"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.97"},{"key":"e_1_2_13_13_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/4241864","article-title":"Application of chimeric antigen receptor T cells in the treatment of hematological malignancies","volume":"2020","author":"Yan W","year":"2020","journal-title":"Biomed Res Int"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.608916"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-019-2118-z"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/mto.2016.11"},{"issue":"1","key":"e_1_2_13_17_1","article-title":"CAR T cells: a snapshot on the growing options to design a CAR","volume":"3","author":"Holzinger A","year":"2019","journal-title":"Hema"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02486"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.6.15.1464371"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0548"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.06.004"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc971"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6123"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370215584936"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0674"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-017-0081-z"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.24"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.05.012"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2015.1046430"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1582"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/acg2.84"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.4"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0735"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-400044"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-0103"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12125"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0079"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1711886"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-02-769208"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13340"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61403-3"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21113906"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2035"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02104"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-021-00418-1"},{"issue":"10","key":"e_1_2_13_46_1","first-page":"802","article-title":"CD19\u2010targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B\u2010cell acute lymphoblastic leukemia","volume":"14","author":"Davila ML","year":"2016","journal-title":"Clin Adv Hematol Oncol"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85309"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31366-0"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-004128"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14061403"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22042150"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv439"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12773"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adro.2018.08.018"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2015.10.003"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2015.12.002"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph7121049"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407222"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.221.221"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709866"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-629527"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2017-0062"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-113714"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2011.1.110"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103849"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac5415"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.05.018"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002936"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-04-842708"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.164"},{"issue":"5","key":"e_1_2_13_71_1","article-title":"CD123 AML targeting by chimeric antigen receptors: a novel magic bullet for AML therapeutics?","volume":"3","author":"Tettamanti S","year":"2014","journal-title":"Onco Targets Ther"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.154"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-20-1030"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2018.10.003"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.52"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126397"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.11.033"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-711903"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2422"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817226"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26792"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V120.21.4042.4042"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1309\/617DWB5GNFWXHW4L"},{"key":"e_1_2_13_84_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-018-0672-7"},{"key":"e_1_2_13_85_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504542"},{"key":"e_1_2_13_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2010.09.002"},{"key":"e_1_2_13_87_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94306"},{"key":"e_1_2_13_88_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1365"},{"key":"e_1_2_13_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.03.014"},{"key":"e_1_2_13_90_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.2025"},{"key":"e_1_2_13_91_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708566"},{"key":"e_1_2_13_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30928-2"},{"key":"e_1_2_13_93_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2508"},{"key":"e_1_2_13_94_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-387969"},{"key":"e_1_2_13_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-020-03198-7"},{"issue":"2","key":"e_1_2_13_96_1","first-page":"117","article-title":"An interim analysis of the ZUMA\u20101 study of KTE\u2010C19 in refractory, aggressive non\u2010Hodgkin lymphoma","volume":"15","author":"Neelapu SS","year":"2017","journal-title":"Clin Adv Hematol Oncol"},{"key":"e_1_2_13_97_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000364"},{"key":"e_1_2_13_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2013.01.003"},{"key":"e_1_2_13_99_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008226"},{"key":"e_1_2_13_100_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707447"},{"key":"e_1_2_13_101_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.745320"},{"key":"e_1_2_13_102_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-019-03685-z"},{"key":"e_1_2_13_103_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0698"},{"key":"e_1_2_13_104_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-017-0400-z"},{"key":"e_1_2_13_105_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-016-0299-5"},{"key":"e_1_2_13_106_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-018-0470-x"},{"key":"e_1_2_13_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.03.001"},{"key":"e_1_2_13_108_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.2604"},{"key":"e_1_2_13_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.100596"},{"key":"e_1_2_13_110_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-12-580068"},{"key":"e_1_2_13_111_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.627549"},{"key":"e_1_2_13_112_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar6711"},{"key":"e_1_2_13_113_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0813-7"},{"key":"e_1_2_13_114_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.780399"},{"key":"e_1_2_13_115_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-020-00599-x"},{"key":"e_1_2_13_116_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta21070"},{"key":"e_1_2_13_117_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25274"},{"key":"e_1_2_13_118_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0184-6"},{"key":"e_1_2_13_119_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.7.7.977"},{"key":"e_1_2_13_120_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.2067"},{"key":"e_1_2_13_121_1","doi-asserted-by":"publisher","DOI":"10.2217\/bmt-2020-0010"},{"key":"e_1_2_13_122_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-017-0423-1"},{"key":"e_1_2_13_123_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0697"},{"key":"e_1_2_13_124_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.09.010"},{"key":"e_1_2_13_125_1","doi-asserted-by":"publisher","DOI":"10.18609\/cgti.2018.028"},{"key":"e_1_2_13_126_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0043"},{"key":"e_1_2_13_127_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84813"},{"key":"e_1_2_13_128_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-628354"},{"key":"e_1_2_13_129_1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elz042"},{"key":"e_1_2_13_130_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2257"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.5551","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.5551","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.5551","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T21:17:04Z","timestamp":1692307024000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.5551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":129,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/cam4.5551"],"URL":"https:\/\/doi.org\/10.1002\/cam4.5551","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,30]]},"assertion":[{"value":"2022-03-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}