{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T21:18:08Z","timestamp":1783804688719,"version":"3.55.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,25]]},"DOI":"10.7759\/cureus.13552","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T16:29:11Z","timestamp":1614270551000},"source":"Crossref","is-referenced-by-count":8,"title":["The Role of Chimeric Antigen Receptor-T Cell Therapy in the Treatment of Hematological Malignancies: Advantages, Trials, and Tribulations, and the Road Ahead"],"prefix":"10.7759","author":[{"given":"Sai","family":"Rohit Reddy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adiona","family":"Llukmani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayat","family":"Hashim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana R","family":"Haddad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dutt S","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrukh","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majdi","family":"Abu Sneineh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domonick K","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0819-1","article-title":"CAR-T \"the living drugs,\" immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy","volume":"12","author":"Liu D","year":"2019","unstructured":"Liu D. CAR-T \"the living drugs,\" immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy. J Hematol Oncol. 2019, 12:113. 10.1186\/s13045-019-0819-1","journal-title":"J Hematol Oncol"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1924379","article-title":"CAR-T cell therapy in cancer: tribulations and road ahead","volume":"2020","author":"Zhang Q","year":"2020","unstructured":"Zhang Q, Ping J, Huang Z, et al.. CAR-T cell therapy in cancer: tribulations and road ahead. J Immunol Res. 2020, 2020:1924379. 10.1155\/2020\/1924379","journal-title":"J Immunol Res"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.03.001","article-title":"The application of CAR-T cell therapy in hematological malignancies: advantages and challenges","volume":"8","author":"Zhao Z","year":"2018","unstructured":"Zhao Z, Chen Y, Francisco NM, Zhang Y, Wu M. The application of CAR-T cell therapy in hematological malignancies: advantages and challenges. Acta Pharm Sin B. 2018, 8:539-551. 10.1016\/j.apsb.2018.03.001","journal-title":"Acta Pharm Sin B"},{"key":"ref4","unstructured":"CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. (2016). Accessed. December 22,2020: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5536094\/."},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3390\/ph7121049","article-title":"Adoptive immunotherapy for hematological malignancies using T cells gene-modified to express tumor antigen-specific receptors","volume":"7","author":"Fujiwara H","year":"2014","unstructured":"Fujiwara H. Adoptive immunotherapy for hematological malignancies using T cells gene-modified to express tumor antigen-specific receptors. Pharmaceuticals. 2014, 7:1049-1068. 10.3390\/ph7121049","journal-title":"Pharmaceuticals"},{"key":"ref6","unstructured":"Leukemia and lymphoma society chimeric antigen receptor (CAR) T-cell therapy. Accessed. December 10, 2020: https:\/\/www.lls.org\/treatment\/types-of-treatment\/immunotherapy\/chimeric-antigen-receptor-car-t-cell-therapy."},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric antigen receptor therapy","volume":"379","author":"June CH","year":"2018","unstructured":"June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018, 379:64-73. 10.1056\/NEJMra1706169","journal-title":"N Engl J Med"},{"key":"ref8","unstructured":"Rutgers Cancer Institute of New Jersey. Advantages of CAR-T cell therapy. Accessed. December 15, 2020: https:\/\/www.cinj.org\/patient-care\/advantages-car-t-cell-therapy."},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.2174\/1381612824666171227222624","article-title":"Safety strategies of genetically engineered T cells in cancer immunotherapy","volume":"24","author":"Ren YB","year":"2018","unstructured":"Ren YB, Sun SJ, Han SY. Safety strategies of genetically engineered T cells in cancer immunotherapy. Curr\u00a0Pharm Des. 2018, 24:78. 10.2174\/1381612824666171227222624","journal-title":"Curr\u00a0Pharm Des"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5474602","article-title":"CAR T cell therapy: a game changer in cancer treatment","volume":"2016","author":"Alm\u00e5sbak H","year":"2016","unstructured":"Alm\u00e5sbak H, Aarvak T, Vemuri MC. CAR T cell therapy: a game changer in cancer treatment. J Immunol Res. 2016, 2016:5474602. 10.1155\/2016\/5474602","journal-title":"J Immunol Res"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-41008-7_10","article-title":"CAR T-cells","volume":"1244","author":"Nair R","year":"2020","unstructured":"Nair R, Westin J. CAR T-cells. Adv Exp Med Biol. 2020, 1244:215-233. 10.1007\/978-3-030-41008-7_10","journal-title":"Adv Exp Med Biol"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1900","article-title":"Chimeric antigen receptor T Cells in hematologic malignancies","volume":"37","author":"Shank BR","year":"2017","unstructured":"Shank BR, Do B, Sevin A, Chen SE, Neelapu SS, Horowitz SB. Chimeric antigen receptor T Cells in hematologic malignancies. Pharmacotherapy. 2017, 37:334-345. 10.1002\/phar.1900","journal-title":"Pharmacotherapy"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061283","article-title":"Killing mechanisms of chimeric antigen receptor (CAR) T cells","volume":"20","author":"Benmebarek MR","year":"2019","unstructured":"Benmebarek MR, Karches CH, Cadilha BL, Lesch S, Endres S, Kobold S. Killing mechanisms of chimeric antigen receptor (CAR) T cells. Int J Mol Sci. 2019, 20:1283. 10.3390\/ijms20061283","journal-title":"Int J Mol Sci"},{"key":"ref14","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 S","year":"2020","unstructured":"Rafiq S, Hackett CS, Brentjens RJ. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat Rev Clin Oncol. 2020, 17:147-167. 10.1038\/s41571-019-0297-y","journal-title":"Nat Rev Clin Oncol"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0460-5","article-title":"Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance","volume":"6","author":"Boyiadzis MM","year":"2018","unstructured":"Boyiadzis MM, Dhodapkar MV, Brentjens RJ, et al.. Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance. J Immunother Cancer. 2018, 6:137. 10.1186\/s40425-018-0460-5","journal-title":"J Immunother Cancer"},{"key":"ref16","unstructured":"Health & medication slideshows. CAR T-cell therapy. a healthcare professional's guide - the top questions answered. (2020). Accessed: December 20, 2020: https:\/\/www.drugs.com\/slideshow\/car-t-cell-therapy-top-10-questions-answered-1288."},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2020-001290","article-title":"CAR-T treatment for hematological malignancies","volume":"68","author":"Atrash S","year":"2020","unstructured":"Atrash S, Bano K, Harrison B, Abdallah AO. CAR-T treatment for hematological malignancies. J Investig Med. 2020, 68:956-964. 10.1136\/jim-2020-001290","journal-title":"J Investig Med"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205010","article-title":"Resistance mechanisms to CAR T-cell therapy and overcoming strategy in B-cell hematologic malignancies","volume":"20","author":"Song MK","year":"2019","unstructured":"Song MK, Park BB, Uhm JE. Resistance mechanisms to CAR T-cell therapy and overcoming strategy in B-cell hematologic malignancies. Int J Mol Sci. 2019, 20:5010. 10.3390\/ijms20205010","journal-title":"Int J Mol Sci"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02250","article-title":"Engineered T cell therapy for cancer in the clinic","volume":"10","author":"Zhao L","year":"2019","unstructured":"Zhao L, Cao YJ. Engineered T cell therapy for cancer in the clinic. Front Immunol. 2019, 10:2250. 10.3389\/fimmu.2019.02250","journal-title":"Front Immunol"},{"key":"ref20","unstructured":"FDA approval brings the first gene therapy to the United States. (2017). Accessed. December 20, 2020: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approval-brings-first-gene-therapy-united-states."},{"key":"ref21","unstructured":"FDA news release FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. (2017). Accessed. December 25, 2020: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-...."},{"key":"ref22","unstructured":"FDA news release FDA approves first cell-based gene therapy for adult patients with relapsed or refractory MCL. (2020). Accessed. December 25, 2020: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-cell-based-gene-therapy-adult-patients-relapse...."},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmrv.2019.01.005","article-title":"Risks and benefits of chimeric antigen receptor T-cell (CAR-T) therapy in cancer: a systematic review and meta-analysis","volume":"33","author":"Grigor EJM","year":"2019","unstructured":"Grigor EJM, Fergusson D, Kekre N, et al.. Risks and benefits of chimeric antigen receptor T-cell (CAR-T) therapy in cancer: a systematic review and meta-analysis. Transfus Med Rev. 2019, 33:98-110. 10.1016\/j.tmrv.2019.01.005","journal-title":"Transfus Med Rev"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545552","article-title":"Adoptive T-cell therapy for cancer: the era of engineered T cells","volume":"45","author":"Bonini C","year":"2015","unstructured":"Bonini C, Mondino A. Adoptive T-cell therapy for cancer: the era of engineered T cells. Eur J Immunol. 2015, 45:2457-2469. 10.1002\/eji.201545552","journal-title":"Eur J Immunol"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000186","article-title":"CAR T cell toxicity: current management and future directions","volume":"3","author":"Y\u00e1\u00f1ez L","year":"2019","unstructured":"Y\u00e1\u00f1ez L, S\u00e1nchez-Escamilla M, Perales MA. CAR T cell toxicity: current management and future directions. Hemasphere. 2019, 3:e186. 10.1097\/HS9.0000000000000186","journal-title":"Hemasphere"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12131","article-title":"Design and development of therapies using chimeric antigen receptor-expressing T cells","volume":"257","author":"Dotti G","year":"2014","unstructured":"Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014, 257:107-126. 10.1111\/imr.12131","journal-title":"Immunol Rev"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1002\/acg2.84","article-title":"TRUCKS, the fourth\u2010generation CAR T cells: current developments and clinical translation","volume":"3","author":"Chmielewski M","year":"2020","unstructured":"Chmielewski M, Abken H. TRUCKS, the fourth\u2010generation CAR T cells: current developments and clinical translation. Adv Cell Gene Ther. 2020, 3:e84. 10.1002\/acg2.84","journal-title":"Adv Cell Gene Ther"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-1057-4","article-title":"Next-generation chimeric antigen receptor T cells: safety strategies to overcome toxicity","volume":"18","author":"Yu S","year":"2019","unstructured":"Yu S, Yi M, Qin S, Wu K. Next-generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Mol Cancer. 2019, 18:125. 10.1186\/s12943-019-1057-4","journal-title":"Mol Cancer"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00555-x","article-title":"Clinical development of CAR T cell therapy in China: 2020 update","author":"Wei J","year":"2020","unstructured":"Wei J, Guo Y, Wang Y, et al.. Clinical development of CAR T cell therapy in China: 2020 update. Cell Mol Immunol. 2020, 10.1038\/s41423-020-00555-x","journal-title":"Cell Mol Immunol"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0028","article-title":"FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome","volume":"23","author":"Le RQ","year":"2018","unstructured":"Le RQ, Li L, Yuan W, et al.. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist. 2018, 23:943-947. 10.1634\/theoncologist.2018-0028","journal-title":"Oncologist"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1038\/mto.2016.11","article-title":"Toxicity and management in CAR T-cell therapy","volume":"3","author":"Bonifant CL","year":"2016","unstructured":"Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics. 2016, 3:16011. 10.1038\/mto.2016.11","journal-title":"Mol Ther Oncolytics"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2018.11.002","article-title":"Recent advances in CAR T-cell toxicity: mechanisms, manifestations, and management","volume":"34","author":"Brudno JN","year":"2019","unstructured":"Brudno JN, Kochenderfer JN. Recent advances in CAR T-cell toxicity: mechanisms, manifestations, and management. Blood Rev. 2019, 34:45-55. 10.1016\/j.blre.2018.11.002","journal-title":"Blood Rev"},{"key":"ref33","unstructured":"Chimeric antigen receptor T-cell therapy. (2020). Accessed. December\u00a030, 2020: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK537294\/."},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Shimabukuro-Vornhagen A","year":"2018","unstructured":"Shimabukuro-Vornhagen A, G\u00f6del P, Subklewe M, et al.. Cytokine release syndrome. J Immunother Cancer. 2018, 6:56. 10.1186\/s40425-018-0343-9","journal-title":"J Immunother Cancer"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2386187","article-title":"Neurotoxicity and cytokine release syndrome after chimeric antigen receptor T cell therapy: insights into mechanisms and novel therapies","volume":"11","author":"Siegler EL","year":"2020","unstructured":"Siegler EL, Kenderian SS. Neurotoxicity and cytokine release syndrome after chimeric antigen receptor T cell therapy: insights into mechanisms and novel therapies. Front Immunol. 2020, 11:1973. 10.1155\/2018\/2386187","journal-title":"Front Immunol"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1586\/ehm.10.46","article-title":"Immunotherapy with CAR-modified T Cells: toxicities and overcoming strategies","volume":"2018","author":"Sun S","year":"2018","unstructured":"Sun S, Hao H, Yang G, Zhang Y, Fu Y. Immunotherapy with CAR-modified T Cells: toxicities and overcoming strategies. J Immunol Res. 2018, 2018:2386187. 10.1586\/ehm.10.46","journal-title":"J Immunol Res"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1586\/ehm.10.46","article-title":"Treatment of graft-versus-host disease with monoclonal antibodies and related fusion proteins","volume":"3","author":"Schroeder T","year":"2010","unstructured":"Schroeder T, Haas R, Kobbe G. Treatment of graft-versus-host disease with monoclonal antibodies and related fusion proteins. Expert Rev Hematol. 2010, 3:633-651. 10.1586\/ehm.10.46","journal-title":"Expert Rev Hematol"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0201-9","article-title":"Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell","volume":"24","author":"Ruella M","year":"2018","unstructured":"Ruella M, Xu J, Barrett DM, et al.. Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nat Med. 2018, 24:1499-1503. 10.1038\/s41591-018-0201-9","journal-title":"Nat Med"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01237","article-title":"Understanding the mechanisms of resistance to CAR T-cell therapy in malignancies","volume":"9","author":"Cheng J","year":"2019","unstructured":"Cheng J, Zhao L, Zhang Y, et al.. Understanding the mechanisms of resistance to CAR T-cell therapy in malignancies. Front Oncol. 2019, 9:1237. 10.3389\/fonc.2019.01237","journal-title":"Front Oncol"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000188","article-title":"CAR-T cells: future perspectives","volume":"3","author":"Charrot S","year":"2019","unstructured":"Charrot S, Hallam S. CAR-T cells: future perspectives. Hemasphere. 2019, 3:e188. 10.1097\/HS9.0000000000000188","journal-title":"Hemasphere"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-019-0152-y","article-title":"Recent advances on blinatumomab for acute lymphoblastic leukemia","volume":"8","author":"Zhao J","year":"2019","unstructured":"Zhao J, Song Y, Liu D. Recent advances on blinatumomab for acute lymphoblastic leukemia. Exp Hematol Oncol. 2019, 8:28. 10.1186\/s40164-019-0152-y","journal-title":"Exp Hematol Oncol"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.09.006","article-title":"Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors","volume":"36","author":"Grosser R","year":"2019","unstructured":"Grosser R, Cherkassky L, Chintala N, Adusumilli PS. Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors. Cancer Cell. 2019, 36:471-482. 10.1016\/j.ccell.2019.09.006","journal-title":"Cancer Cell"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00910-5","article-title":"Recent advances in CAR-T cell engineering","volume":"13","author":"Huang R","year":"2020","unstructured":"Huang R, Li X, He Y, et al.. Recent advances in CAR-T cell engineering. J Hematol Oncol. 2020, 13:86. 10.1186\/s13045-020-00910-5","journal-title":"J Hematol Oncol"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113139","article-title":"Natural killer cells in immunotherapy: are we nearly there?","volume":"12","author":"Bachiller M","year":"2020","unstructured":"Bachiller M, Battram AM, Perez-Amill L, Mart\u00edn-Antonio B. Natural killer cells in immunotherapy: are we nearly there?. Cancers (Basel). 2020, 12:3139. 10.3390\/cancers12113139","journal-title":"Cancers (Basel)"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.3486","article-title":"Chimeric antigen receptor T-cell therapy: a beacon of hope in the fight against cancer","volume":"10","author":"Tariq S","year":"2018","unstructured":"Tariq S, Haider S, Hasan M, Tahir A, Khan M, Rehan A, Kamal A. Chimeric antigen receptor T-cell therapy: a beacon of hope in the fight against cancer. Cureus. 2018, 10:3486. 10.7759\/cureus.3486","journal-title":"Cureus"},{"key":"ref46","unstructured":"U.S. FDA approves kite\u2019s tecartus\u2122, the first and only CAR T treatment for relapsed or refractory mantle cell lymphoma. (2020). Accessed. December\u00a030, 2020: https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2020\/7\/us-fda-approves-kites-tecartus-the-first-and-o...."}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/50988-the-role-of-chimeric-antigen-receptor-t-cell-therapy-in-the-treatment-of-hematological-malignancies-advantages-trials-and-tribulations-and-the-road-ahead","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T19:24:50Z","timestamp":1707506690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/50988-the-role-of-chimeric-antigen-receptor-t-cell-therapy-in-the-treatment-of-hematological-malignancies-advantages-trials-and-tribulations-and-the-road-ahead"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":46,"URL":"https:\/\/doi.org\/10.7759\/cureus.13552","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2021,2,25]]}}}