Abstract
CAR T-cell therapy is a promising approach for cancer treatment, utilizing a patient's own T-cells (autologous cell) or T-cells from a healthy donor (allogeneic cell) to target and destroy cancer cells. Over the last decade, significant advancements have been made in this field, including the development of novel CAR constructs, improved understanding of biology and mechanisms of action, and expanded clinical applications for treating a wider range of cancers. In this review, we provide an overview of the steps involved in the production of CAR T-cells and their mechanism of action. We also introduce different CAR T-cell therapies available, including their implementation, dosage, administration, treatment cost, efficacy, and resistance. Common side effects of CAR T-cell therapy are also discussed. The CAR T-cell products highlighted in this review are FDA-approved products, which include Kymriah® (tisagenlecleucel), Tecartus® (brexucabtagene autoleucel), Abecma® (Idecabtagene vicleucel), Breyanzi® (lisocabtagene maraleucel), and Yescarta® (axicabtagene ciloleucel). In conclusion, CAR T-cell therapy has made tremendous progress over the past decade and has the potential to revolutionize cancer treatment. This review paper provides insights into the progress, challenges, and future directions of CAR T-cell therapy, offering valuable information for researchers, clinicians, and patients.
Graphical Abstract
[http://dx.doi.org/10.1155/2016/5474602] [PMID: 27298832]
[http://dx.doi.org/10.1186/s13045-020-00910-5] [PMID: 32616000]
[http://dx.doi.org/10.3389/fimmu.2019.00456] [PMID: 30941126]
[http://dx.doi.org/10.1200/JCO.20.01467] [PMID: 33021872]
[http://dx.doi.org/10.15419/bmrat.v9i2.726]
[http://dx.doi.org/10.1038/nature22395] [PMID: 28541315]
[http://dx.doi.org/10.1038/s41591-022-02182-7] [PMID: 36690811]
[http://dx.doi.org/10.1016/S0140-6736(20)32334-5] [PMID: 33308471]
[http://dx.doi.org/10.3390/ijms21113906] [PMID: 32486160]
[http://dx.doi.org/10.1182/blood.2022015526] [PMID: 36095849]
[http://dx.doi.org/10.1016/j.omtm.2016.12.006] [PMID: 28344995]
[http://dx.doi.org/10.1038/mto.2016.15] [PMID: 27347557]
[http://dx.doi.org/10.1186/1476-4598-13-219] [PMID: 25241075]
[http://dx.doi.org/10.1038/s41467-022-32866-0] [PMID: 36064867]
[http://dx.doi.org/10.3390/ijms20061283] [PMID: 30875739]
[http://dx.doi.org/10.1634/theoncologist.2019-0233] [PMID: 32043764]
[http://dx.doi.org/10.3390/v13081528]
[http://dx.doi.org/10.1001/jamaoncol.2018.0977] [PMID: 29710129]
[http://dx.doi.org/10.1001/jamanetworkopen.2020.2072] [PMID: 32250433]
[http://dx.doi.org/10.1016/j.jtct.2021.03.005] [PMID: 33823168]
[http://dx.doi.org/10.1200/JCO.22.00642] [PMID: 36399695]
[http://dx.doi.org/10.1056/NEJMoa1709866] [PMID: 29385370]
[http://dx.doi.org/10.1158/1078-0432.CCR-18-2035] [PMID: 30309857]
[http://dx.doi.org/10.1186/s40164-022-00268-z] [PMID: 35337365]
[http://dx.doi.org/10.1056/NEJMoa1804980] [PMID: 30501490]
[http://dx.doi.org/10.1182/blood-2019-129120]
[http://dx.doi.org/10.1002/hon.85_2879]
[http://dx.doi.org/10.1056/NEJMoa2116596] [PMID: 34904798]
[http://dx.doi.org/10.1158/2159-8290.CD-19-0813] [PMID: 32001516]
[http://dx.doi.org/10.1097/01.COT.0000872268.55217.67]
[http://dx.doi.org/10.1001/jama.2020.15456] [PMID: 32870282]
[http://dx.doi.org/10.1080/13696998.2021.1894158] [PMID: 33634729]
[http://dx.doi.org/10.1056/NEJMoa1914347] [PMID: 32242358]
[http://dx.doi.org/10.2147/OTT.S155778] [PMID: 31686856]
[http://dx.doi.org/10.2147/TCRM.S72943] [PMID: 26609233]
[http://dx.doi.org/10.1182/bloodadvances.2020003698] [PMID: 34638136]
[http://dx.doi.org/10.1007/s00277-015-2478-9] [PMID: 26411584]
[http://dx.doi.org/10.51731/cjht.2022.250]
[http://dx.doi.org/10.1007/s11899-021-00635-3] [PMID: 34089485]
[http://dx.doi.org/10.1056/NEJMoa1817226] [PMID: 31042825]
[http://dx.doi.org/10.3389/fimmu.2021.632937] [PMID: 33717171]
[http://dx.doi.org/10.1056/NEJMoa2024850] [PMID: 33626253]
[http://dx.doi.org/10.1097/MD.0000000000025784] [PMID: 33950974]
[http://dx.doi.org/10.1158/2326-6066.CIR-18-0551] [PMID: 31113804]
[http://dx.doi.org/10.1038/s41467-021-21177-5] [PMID: 33558511]
[http://dx.doi.org/10.1038/s41591-021-01245-5] [PMID: 33619368]
[http://dx.doi.org/10.1172/JCI126397] [PMID: 30896447]
[http://dx.doi.org/10.1038/s43018-021-00241-5] [PMID: 34485921]
[http://dx.doi.org/10.3389/fimmu.2020.01128] [PMID: 32582204]
[http://dx.doi.org/10.3389/fonc.2020.01362] [PMID: 32850436]
[http://dx.doi.org/10.1038/s41408-022-00716-3] [PMID: 35973981]
[http://dx.doi.org/10.1016/S2352-3026(21)00057-0] [PMID: 34048683]
[http://dx.doi.org/10.7573/dic.212567] [PMID: 30815024]
[http://dx.doi.org/10.1002/cpt.2561]
[http://dx.doi.org/10.1016/j.hemonc.2021.09.004] [PMID: 34699774]
[http://dx.doi.org/10.1002/ajh.26151] [PMID: 33661537]
[http://dx.doi.org/10.1002/ajh.26301] [PMID: 34310745]
[http://dx.doi.org/10.1016/S0140-6736(20)31366-0] [PMID: 32888407]
[http://dx.doi.org/10.1080/13696998.2018.1529674] [PMID: 30260711]
[http://dx.doi.org/10.1097/HS9.0000000000000524] [PMID: 33880433]
[http://dx.doi.org/10.1182/bloodadvances.2020003848] [PMID: 34478487]
[http://dx.doi.org/10.1056/NEJMoa1707447] [PMID: 29226797]
[http://dx.doi.org/10.1016/S1470-2045(18)30864-7] [PMID: 30518502]
[http://dx.doi.org/10.1016/S1470-2045(21)00591-X] [PMID: 34895487]
[http://dx.doi.org/10.1186/s13046-022-02327-z]
[http://dx.doi.org/10.1016/j.imlet.2019.05.003] [PMID: 31091431]
[http://dx.doi.org/10.7861/clinmedicine.18-4-324] [PMID: 30072559]
[http://dx.doi.org/10.1038/mto.2016.11] [PMID: 27626062]
[http://dx.doi.org/10.1146/annurev-pathol-020117-043625]
[http://dx.doi.org/10.1016/j.annonc.2020.10.478] [PMID: 33098993]