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Volume 31, Issue 13
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Cancer is a significant health challenge worldwide, causing social and economic burdens. Despite advancements in medicine, it remains a leading cause of death and is projected to increase by 2040. While conventional treatments like surgery, radiation, and chemotherapy are effective, they often have severe side effects. CAR T-cell (chimeric antigen receptor T-cell) treatment is a novel immunotherapy method personalized to the patient's immune system and directly targets cancer cells. It originated in the 1980s, and advancements have made it more effective. However, challenges remain, such as severe side effects, high costs, and manufacturing variability. Despite these challenges, the treatment with CAR T-cells has shown remarkable success, especially in hematologic malignancies. Though, it is new to solid tumours, ongoing research looks promising. CAR T-cell therapy offers hope for fightingcancer, and it stands poised to redefine cancer treatment paradigms, giving renewed optimism to patients globally.

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References

  1. MattiuzziC. LippiG. Current cancer epidemiology.J. Epidemiol. Glob. Health20199421722210.2991/jegh.k.191008.00131854162
     [Google Scholar]
  2. SharmaP. JhawatV. MathurP. DuttR. Innovation in cancer therapeutics and regulatory perspectives.Med. Oncol.202223957610.1007/s12032‑022‑01677‑035195787
     [Google Scholar]
  3. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
     [Google Scholar]
  4. SternerR.C. SternerR.M. CAR-T cell therapy: Current limitations and potential strategies.Blood Cancer J.11469202110.1038/s41408‑021‑00459‑733824268
     [Google Scholar]
  5. WaldmanA.D. FritzJ.M. LenardoM.J. A guide to cancer immunotherapy: From T cell basic science to clinical practice.Nat. Rev. Immunol.2020201165166810.1038/s41577‑020‑0306‑532433532
     [Google Scholar]
  6. KeyvaniV. RiahiE. YousefiM. EsmaeiliS.A. ShafabakhshR. Moradi Hasan-AbadA. Mahjoubin-TehranM. HamblinM.R. MollazadehS. MirzaeiH. Gynecologic cancer, cancer stem cells, and possible targeted therapies.Front. Pharmacol.20221382357210.3389/fphar.2022.82357235250573
     [Google Scholar]
  7. GarridoF. AptsiauriN. DoorduijnE.M. Garcia LoraA.M. van HallT. The urgent need to recover MHC class I in cancers for effective immunotherapy.Curr. Opin. Immunol.201639445110.1016/j.coi.2015.12.00726796069
     [Google Scholar]
  8. KuwanaY. AsakuraY. UtsunomiyaN. NakanishiM. ArataY. ItohS. NagaseF. KurosawaY. Expression of chimeric receptor composed of immunoglobulin-derived V resions and T-cell receptor-derived C regions.Biochem. Biophys. Res. Commun.1987149396096810.1016/0006‑291X(87)90502‑X3122749
     [Google Scholar]
  9. BrudnoJ.N. KochenderferJ.N. Toxicities of chimeric antigen receptor T cells: Recognition and management.Blood2016127263321333010.1182/blood‑2016‑04‑70375127207799
     [Google Scholar]
  10. GruppS.A. KalosM. BarrettD. AplencR. PorterD.L. RheingoldS.R. TeacheyD.T. ChewA. HauckB. WrightJ.F. MiloneM.C. LevineB.L. JuneC.H. Chimeric antigen receptor- modified T cells for acute lymphoid leukemia.N. Engl. J. Med.2013368161509151810.1056/NEJMoa121513423527958
     [Google Scholar]
  11. NeelapuS.S. TummalaS. KebriaeiP. WierdaW. GutierrezC. LockeF.L. KomanduriK.V. LinY. JainN. DaverN. WestinJ. GulbisA.M. LoghinM.E. de GrootJ.F. AdkinsS. DavisS.E. RezvaniK. HwuP. ShpallE.J. Chimeric antigen receptor T-cell therapy - Assessment and management of toxicities.Nat. Rev. Clin. Oncol.2018151476210.1038/nrclinonc.2017.14828925994
     [Google Scholar]
  12. HernandezI. PrasadV. GelladW.F. Total costs of chimeric antigen receptor T-cell immunotherapy.JAMA Oncol.20184799499610.1001/jamaoncol.2018.097729710129
     [Google Scholar]
  13. VormittagP. GunnR. GhorashianS. VeraitchF.S. A guide to manufacturing CAR T cell therapies.Curr. Opin. Biotechnol.20185316418110.1016/j.copbio.2018.01.02529462761
     [Google Scholar]
  14. BrentjensR.J. DavilaM.L. RiviereI. CD19-targeted T Cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia.Sci. Transl. Med.20135177177ra3810.1126/scitranslmed.3005930
     [Google Scholar]
  15. CohenA.D. GarfallA.L. StadtmauerE.A. MelenhorstJ.J. LaceyS.F. LancasterE. VoglD.T. WeissB.M. DengelK. NelsonA. PlesaG. ChenF. DavisM.M. HwangW.T. YoungR.M. BrogdonJ.L. IsaacsR. Pruteanu-MaliniciI. SiegelD.L. LevineB.L. JuneC.H. MiloneM.C. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma.J. Clin. Invest.201912962210222110.1172/JCI12639730896447
     [Google Scholar]
  16. KoneruM. O’CearbhaillR. PendharkarS. SpriggsD.R. BrentjensR.J. A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16ecto directed chimeric antigen receptors for recurrent ovarian cancer.J. Transl. Med.201513110210.1186/s12967‑015‑0460‑x25890361
     [Google Scholar]
  17. MajznerR.G. TheruvathJ.L. NellanA. HeitzenederS. CuiY. MountC.W. RietbergS.P. LindeM.H. XuP. RotaC. SotilloE. LabaniehL. LeeD.W. OrentasR.J. DimitrovD.S. ZhuZ. CroixB.S. DelaidelliA. SekunovaA. BonviniE. MitraS.S. QuezadoM.M. MajetiR. MonjeM. SorensenP.H.B. MarisJ.M. MackallC.L. CAR T cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors.Clin. Cancer Res.20192582560257410.1158/1078‑0432.CCR‑18‑043230655315
     [Google Scholar]
  18. NeelapuS.S. LockeF.L. BartlettN.L. LekakisL.J. MiklosD.B. JacobsonC.A. BraunschweigI. OluwoleO.O. SiddiqiT. LinY. TimmermanJ.M. StiffP.J. FriedbergJ.W. FlinnI.W. GoyA. HillB.T. SmithM.R. DeolA. FarooqU. McSweeneyP. MunozJ. AviviI. CastroJ.E. WestinJ.R. ChavezJ.C. GhobadiA. KomanduriK.V. LevyR. JacobsenE.D. WitzigT.E. ReaganP. BotA. RossiJ. NavaleL. JiangY. AycockJ. EliasM. ChangD. WiezorekJ. GoW.Y. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma.N. Engl. J. Med.2017377262531254410.1056/NEJMoa170744729226797
     [Google Scholar]
  19. PorterD.L. LevineB.L. KalosM. BaggA. JuneC.H. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia.N. Engl. J. Med.2011365872573310.1056/NEJMoa110384921830940
     [Google Scholar]
  20. RajeN. BerdejaJ. LinY. SiegelD. JagannathS. MadduriD. LiedtkeM. RosenblattJ. MausM.V. TurkaA. LamL.P. MorganR.A. FriedmanK. MassaroM. WangJ. RussottiG. YangZ. CampbellT. HegeK. PetroccaF. QuigleyM.T. MunshiN. KochenderferJ.N. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma.N. Engl. J. Med.2019380181726173710.1056/NEJMoa181722631042825
     [Google Scholar]
  21. van SchalkwykM.C.I. PapaS.E. JeannonJ.P. UrbanoT.G. SpicerJ.F. MaherJ. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer.Hum. Gene Ther. Clin. Dev.201324313414210.1089/humc.2013.14424099518
     [Google Scholar]
  22. YekuO.O. PurdonT.J. KoneruM. SpriggsD. BrentjensR.J. Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment.Sci. Rep.2017711054110.1038/s41598‑017‑10940‑828874817
     [Google Scholar]
  23. AtabatiH. YazdanpanahE. MortazaviH. bajestaniS.G. RaoofiA. EsmaeiliS.A. KhalediA. SaburiE. AfshariJ.T. SathyapalanT. MoghaddamA.S. SahebkarA. Immunoregulatory effects of tolerogenic probiotics in multiple sclerosis.Adv. Exp. Med. Biol.20211286Part II8710510.1007/978‑3‑030‑55035‑6_633725347
     [Google Scholar]
  24. GrossG. WaksT. EshharZ. Expression of immunoglobulin-T- cell receptor chimeric molecules as functional receptors with antibody-type specificity.Proc. Natl. Acad. Sci. USA19898624100241002810.1073/pnas.86.24.100242513569
     [Google Scholar]
  25. EshharZ. WaksT. GrossG. SchindlerD.G. 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.Proc. Natl. Acad. Sci. USA199390272072410.1073/pnas.90.2.7208421711
     [Google Scholar]
  26. BirdR.E. HardmanK.D. JacobsonJ.W. JohnsonS. KaufmanB.M. LeeS.M. LeeT. PopeS.H. RiordanG.S. WhitlowM. Single-chain antigen-binding proteins.Science1988242487742342610.1126/science.31403793140379
     [Google Scholar]
  27. HustonJ.S. LevinsonD. Mudgett-HunterM. TaiM.S. NovotnýJ. MargoliesM.N. RidgeR.J. BruccoleriR.E. HaberE. CreaR. Protein engineering of antibody binding sites: Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in Escherichia coli.Proc. Natl. Acad. Sci. USA198885165879588310.1073/pnas.85.16.58793045807
     [Google Scholar]
  28. EshharZ. Tumor-specific T-bodies: Towards clinical application.Cancer Immunol. Immunother.1997453-413113610.1007/s0026200504159435856
     [Google Scholar]
  29. RosenbaumL. Tragedy, perseverance, and chance - The story of CAR-T therapy.N. Engl. J. Med.2017377141313131510.1056/NEJMp171188628902570
     [Google Scholar]
  30. MaudeS.L. FreyN. ShawP.A. AplencR. BarrettD.M. BuninN.J. ChewA. GonzalezV.E. ZhengZ. LaceyS.F. MahnkeY.D. MelenhorstJ.J. RheingoldS.R. ShenA. TeacheyD.T. LevineB.L. JuneC.H. PorterD.L. GruppS.A. Chimeric antigen receptor T cells for sustained remissions in leukemia.N. Engl. J. Med.2014371161507151710.1056/NEJMoa140722225317870
     [Google Scholar]
  31. MaudeS.L. LaetschT.W. BuechnerJ. RivesS. BoyerM. BittencourtH. BaderP. VernerisM.R. StefanskiH.E. MyersG.D. QayedM. De MoerlooseB. HiramatsuH. SchlisK. DavisK.L. MartinP.L. NemecekE.R. YanikG.A. PetersC. BaruchelA. BoisselN. MechinaudF. BalduzziA. KruegerJ. JuneC.H. LevineB.L. WoodP. TaranT. LeungM. MuellerK.T. ZhangY. SenK. LebwohlD. PulsipherM.A. GruppS.A. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia.N. Engl. J. Med.2018378543944810.1056/NEJMoa170986629385370
     [Google Scholar]
  32. ParkJ.H. RivièreI. GonenM. WangX. SénéchalB. CurranK.J. SauterC. WangY. SantomassoB. MeadE. RoshalM. MaslakP. DavilaM. BrentjensR.J. SadelainM. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia.N. Engl. J. Med.2018378544945910.1056/NEJMoa170991929385376
     [Google Scholar]
  33. PorterD.L. HwangW.-T. FreyN.V. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia.Sci. Transl. Med.20157303303ra13910.1126/scitranslmed.aac5415
     [Google Scholar]
  34. SchusterS.J. SvobodaJ. ChongE.A. NastaS.D. MatoA.R. AnakÖ. BrogdonJ.L. Pruteanu-MaliniciI. BhojV. LandsburgD. WasikM. LevineB.L. LaceyS.F. MelenhorstJ.J. PorterD.L. JuneC.H. Chimeric antigen receptor T cells in refractory B-cell lymphomas.N. Engl. J. Med.2017377262545255410.1056/NEJMoa170856629226764
     [Google Scholar]
  35. FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome.2017Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisagenlecleucel-b-cell-all-and-tocilizumab-cytokine-release-syndrome
  36. FDA approves tisagenlecleucel for adults with relapsed or refractory large B-cell lymphoma.2018Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisagenlecleucel-adults-relapsed-or-refractory-large-b-cell-lymphoma?elqTrackId=5578022d641d45d5a723adaf982a493c&elq=933c3d8ba491426680135d5ae119dcc6&elqaid=3339&elqat=1&e=
  37. SchepisiG. CursanoM.C. CasadeiC. MennaC. AltavillaA. LolliC. CerchioneC. PaganelliG. SantiniD. ToniniG. MartinelliG. De GiorgiU. CAR-T cell therapy: A potential new strategy against prostate cancer.J. Immunother. Cancer20197125810.1186/s40425‑019‑0741‑731619289
     [Google Scholar]
  38. Ruiz-GarciaE. Astudillo-de la VegaH. Translational research and onco-omics applications in the era of cancer personal genomics.SpringerCham201910.1007/978‑3‑030‑24100‑1
     [Google Scholar]
  39. JensenM.C. PopplewellL. CooperL.J. Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans.Biol. Blood Marrow Transplant.20101691245125610.1016/j.bbmt.2010.03.014
     [Google Scholar]
  40. ThistlethwaiteF.C. GilhamD.E. GuestR.D. RothwellD.G. PillaiM. BurtD.J. ByatteA.J. KirillovaN. ValleJ.W. SharmaS.K. ChesterK.A. WestwoodN.B. HalfordS.E.R. NabarroS. WanS. AustinE. HawkinsR.E. The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity.Cancer Immunol. Immunother.201766111425143610.1007/s00262‑017‑2034‑728660319
     [Google Scholar]
  41. SavoldoB. RamosC.A. LiuE. MimsM.P. KeatingM.J. CarrumG. KambleR.T. BollardC.M. GeeA.P. MeiZ. LiuH. GrilleyB. RooneyC.M. HeslopH.E. BrennerM.K. DottiG. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients.J. Clin. Invest.201112151822182610.1172/JCI4611021540550
     [Google Scholar]
  42. ZhongX.S. MatsushitaM. PlotkinJ. RiviereI. SadelainM. Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/Akt/Bcl-XL activation and CD8+ T cell-mediated tumor eradication.Mol. Ther.201018241342010.1038/mt.2009.21019773745
     [Google Scholar]
  43. ChmielewskiM. AbkenH. TRUCKS, the fourth-generation CAR T cells: Current developments and clinical translation.Adv. Cell Gene Ther.202033e8410.1002/acg2.84
     [Google Scholar]
  44. KagoyaY. TanakaS. GuoT. AnczurowskiM. WangC.H. SasoK. ButlerM.O. MindenM.D. HiranoN. A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects.Nat. Med.201824335235910.1038/nm.447829400710
     [Google Scholar]
  45. HonikelM.M. OlejniczakS.H. Co-stimulatory receptor signaling in CAR-T cells.Biomolecules2022129130310.3390/biom1209130336139142
     [Google Scholar]
  46. ParkJ.H. RiviereI. WangX. Efficacy and safety of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed or refractory B-ALL.J. Clin. Oncol.201533Suppl 1510.1200/jco.2015.33.15_suppl.7010
     [Google Scholar]
  47. LeeD.W. KochenderferJ.N. Stetler-StevensonM. CuiY.K. DelbrookC. FeldmanS.A. FryT.J. OrentasR. SabatinoM. ShahN.N. SteinbergS.M. StroncekD. TscherniaN. YuanC. ZhangH. ZhangL. RosenbergS.A. WayneA.S. MackallC.L. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial.Lancet2015385996751752810.1016/S0140‑6736(14)61403‑325319501
     [Google Scholar]
  48. ShahN.N. LeeD.W. YatesB. YuanC.M. ShalabiH. MartinS. WoltersP.L. SteinbergS.M. BakerE.H. DelbrookC.P. Stetler-StevensonM. FryT.J. StroncekD.F. MackallC.L. Long-term follow-up of CD19- CAR T-cell therapy in children and young adults with B-ALL.J. Clin. Oncol.202139151650165910.1200/JCO.20.0226233764809
     [Google Scholar]
  49. TurtleC.J. HanafiL.A. BergerC. GooleyT.A. CherianS. HudecekM. SommermeyerD. MelvilleK. PenderB. BudiartoT.M. RobinsonE. SteevensN.N. ChaneyC. SomaL. ChenX. YeungC. WoodB. LiD. CaoJ. HeimfeldS. JensenM.C. RiddellS.R. MaloneyD.G. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients.J. Clin. Invest.201612662123213810.1172/JCI8530927111235
     [Google Scholar]
  50. SabatinoM. ChoiK. ChiruvoluV. BetterM. Production of anti-CD19 CAR T cells for ZUMA-3 and-4: Phase 1/2 multicenter studies evaluating KTE-C19 in patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (R/R ALL).Blood201612822122710.1182/blood.V128.22.1227.1227
     [Google Scholar]
  51. ShahB.D. BishopM.R. OluwoleO.O. LoganA.C. BaerM.R. DonnellanW.B. O’DwyerK.M. HolmesH. ArellanoM.L. GhobadiA. PagelJ.M. LinY. CassadayR.D. ParkJ.H. AbediM. CastroJ.E. DeAngeloD.J. MaloneA.K. MawadR. SchillerG.J. RossiJ.M. BotA. ShenT. GoyalL. JainR.K. VezanR. WierdaW.G. KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results.Blood20211381112210.1182/blood.202000909833827116
     [Google Scholar]
  52. ShahB.D. GhobadiA. OluwoleO.O. LoganA.C. BoisselN. CassadayR.D. LeguayT. BishopM.R. ToppM.S. TzachanisD. O’DwyerK.M. ArellanoM.L. LinY. BaerM.R. SchillerG.J. ParkJ.H. SubkleweM. AbediM. MinnemaM.C. WierdaW.G. DeAngeloD.J. StiffP. JeyakumarD. FengC. DongJ. ShenT. MillettiF. RossiJ.M. VezanR. MasoulehB.K. HouotR. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: Phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study.Lancet20213981029949150210.1016/S0140‑6736(21)01222‑834097852
     [Google Scholar]
  53. DavilaM.L. SadelainM. Biology and clinical application of CAR T cells for B cell malignancies.Int. J. Hematol.2016104161710.1007/s12185‑016‑2039‑627262700
     [Google Scholar]
  54. ShalabiH. AngiolilloA. FryT.J. Beyond CD19: Opportunities for future development of targeted immunotherapy in pediatric relapsed-refractory acute leukemia.Front Pediatr.201538010.3389/fped.2015.0008026484338
     [Google Scholar]
  55. BurgerJ.A. TedeschiA. BarrP.M. RobakT. OwenC. GhiaP. BaireyO. HillmenP. BartlettN.L. LiJ. SimpsonD. GrosickiS. DevereuxS. McCarthyH. CoutreS. QuachH. GaidanoG. MaslyakZ. StevensD.A. JanssensA. OffnerF. MayerJ. O’DwyerM. HellmannA. SchuhA. SiddiqiT. PolliackA. TamC.S. SuriD. ChengM. ClowF. StylesL. JamesD.F. KippsT.J. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia.N. Engl. J. Med.2015373252425243710.1056/NEJMoa150938826639149
     [Google Scholar]
  56. TurtleC.J. HayK.A. HanafiL.A. LiD. CherianS. ChenX. WoodB. LozanskiA. ByrdJ.C. HeimfeldS. RiddellS.R. MaloneyD.G. Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib.J. Clin. Oncol.201735263010302010.1200/JCO.2017.72.851928715249
     [Google Scholar]
  57. FreyN.V. GillS. HexnerE.O. SchusterS. NastaS. LorenA. SvobodaJ. StadtmauerE. LandsburgD.J. MatoA. LevineB.L. LaceyS.F. MelenhorstJ.J. VelosoE. GaymonA. PequignotE. ShanX. HwangW.T. JuneC.H. PorterD.L. Long-term outcomes from a randomized dose optimization study of chimeric antigen receptor modified T cells in relapsed chronic lymphocytic leukemia.J. Clin. Oncol.202038252862287110.1200/JCO.19.0323732298202
     [Google Scholar]
  58. TodorovicZ. TodorovicD. MarkovicV. LadjevacN. ZdravkovicN. DjurdjevicP. ArsenijevicN. MilovanovicM. ArsenijevicA. MilovanovicJ. CAR T cell therapy for chronic lymphocytic leukemia: Successes and shortcomings.Curr. Oncol.20222953647365710.3390/curroncol2905029335621683
     [Google Scholar]
  59. LockeF.L. MiklosD.B. JacobsonC.A. PeralesM.A. KerstenM.J. OluwoleO.O. GhobadiA. RapoportA.P. McGuirkJ. PagelJ.M. MuñozJ. FarooqU. van MeertenT. ReaganP.M. SuredaA. FlinnI.W. VandenbergheP. SongK.W. DickinsonM. MinnemaM.C. RiedellP.A. LeslieL.A. ChagantiS. YangY. FilostoS. ShahJ. SchuppM. ToC. ChengP. GordonL.I. WestinJ.R. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma.N. Engl. J. Med.2022386764065410.1056/NEJMoa211613334891224
     [Google Scholar]
  60. AbramsonJ.S. PalombaM.L. GordonL.I. LunningM.A. WangM. ArnasonJ. MehtaA. PurevE. MaloneyD.G. AndreadisC. SehgalA. SolomonS.R. GhoshN. AlbertsonT.M. GarciaJ. KosticA. MallaneyM. OgasawaraK. NewhallK. KimY. LiD. SiddiqiT. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study.Lancet20203961025483985210.1016/S0140‑6736(20)31366‑032888407
     [Google Scholar]
  61. KamdarM. SolomonS.R. ArnasonJ. JohnstonP.B. GlassB. BachanovaV. IbrahimiS. MielkeS. MutsaersP. Hernandez-IlizaliturriF. IzutsuK. MorschhauserF. LunningM. MaloneyD.G. CrottaA. MontheardS. PrevitaliA. StepanL. OgasawaraK. MackT. AbramsonJ.S. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial.Lancet2022399103432294230810.1016/S0140‑6736(22)00662‑635717989
     [Google Scholar]
  62. SchusterS.J. TamC.S. BorchmannP. WorelN. McGuirkJ.P. HolteH. WallerE.K. JaglowskiS. BishopM.R. DamonL.E. FoleyS.R. WestinJ.R. FleuryI. HoP.J. MielkeS. TeshimaT. JanakiramM. HsuJ.M. IzutsuK. KerstenM.J. GhoshM. Wagner-JohnstonN. KatoK. CorradiniP. Martinez-PrietoM. HanX. TiwariR. SallesG. MaziarzR.T. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): A multicentre, open-label, single-arm, phase 2 study.Lancet Oncol.202122101403141510.1016/S1470‑2045(21)00375‑234516954
     [Google Scholar]
  63. SehgalA. HodaD. RiedellP.A. GhoshN. HamadaniM. HildebrandtG.C. GodwinJ.E. ReaganP.M. Wagner-JohnstonN. EssellJ. NathR. SolomonS.R. ChampionR. LicitraE. FanningS. GuptaN. DubowyR. D’AndreaA. WangL. OgasawaraK. ThorpeJ. GordonL.I. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B- cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): An open-label, phase 2 study.Lancet Oncol.20222381066107710.1016/S1470‑2045(22)00339‑435839786
     [Google Scholar]
  64. GarfallA.L. MausM.V. HwangW.T. LaceyS.F. MahnkeY.D. MelenhorstJ.J. ZhengZ. VoglD.T. CohenA.D. WeissB.M. DengelK. KerrN.D.S. BaggA. LevineB.L. JuneC.H. StadtmauerE.A. Chimeric antigen receptor T cells against CD19 for multiple myeloma.N. Engl. J. Med.2015373111040104710.1056/NEJMoa150454226352815
     [Google Scholar]
  65. SchellerL. TebukaE. RambauP.F. BCMA CAR-T cells in multiple myeloma-ready for take-off?Leuk. Lymphoma202465214315710.1080/10428194.2023.2276676
     [Google Scholar]
  66. D’AloiaM.M. ZizzariI.G. SacchettiB. PierelliL. AlimandiM. CAR-T cells: The long and winding road to solid tumors.Cell Death Dis.20189328210.1038/s41419‑018‑0278‑629449531
     [Google Scholar]
  67. FiorentinoA. BonisP.D. ChiesaS. BalducciM. FuscoV. Elderly patients with glioblastoma: The treatment challenge.Expert Rev. Neurother.201313101099110510.1586/14737175.2013.84041924117272
     [Google Scholar]
  68. RodriguezA. BrownC. BadieB. Chimeric antigen receptor T-cell therapy for glioblastoma.Transl. Res.20171879310210.1016/j.trsl.2017.07.00328755873
     [Google Scholar]
  69. BrownC.E. AlizadehD. StarrR. WengL. WagnerJ.R. NaranjoA. OstbergJ.R. BlanchardM.S. KilpatrickJ. SimpsonJ. KurienA. PricemanS.J. WangX. HarshbargerT.L. D’ApuzzoM. ResslerJ.A. JensenM.C. BarishM.E. ChenM. PortnowJ. FormanS.J. BadieB. Regression of glioblastoma after chimeric antigen receptor T-Cell therapy.N. Engl. J. Med.2016375262561256910.1056/NEJMoa161049728029927
     [Google Scholar]
  70. KlampatsaA. DimouV. AlbeldaS.M. Mesothelin-targeted CAR-T cell therapy for solid tumors.Expert Opin. Biol. Ther.202121447348610.1080/14712598.2021.184362833176519
     [Google Scholar]
  71. MorganR.A. YangJ.C. KitanoM. DudleyM.E. LaurencotC.M. RosenbergS.A. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2.Mol. Ther.201018484385110.1038/mt.2010.24
     [Google Scholar]
  72. AhmedN. BrawleyV.S. HegdeM. RobertsonC. GhaziA. GerkenC. LiuE. DakhovaO. AshooriA. CorderA. GrayT. WuM.F. LiuH. HicksJ. RainussoN. DottiG. MeiZ. GrilleyB. GeeA. RooneyC.M. BrennerM.K. HeslopH.E. WelsW.S. WangL.L. AndersonP. GottschalkS. Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified T Cells for the immunotherapy of HER2-positive sarcoma.J. Clin. Oncol.201533151688169610.1200/JCO.2014.58.022525800760
     [Google Scholar]
  73. KatzS.C. MoodyA.E. GuhaP. HardawayJ.C. PrinceE. LaPorteJ. StancuM. SlanskyJ.E. JordanK.R. SchulickR.D. KnightR. SaiedA. ArmenioV. JunghansR.P. HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery.J. Immunother. Cancer202082e00109710.1136/jitc‑2020‑00109732843493
     [Google Scholar]
  74. KershawM.H. WestwoodJ.A. ParkerL.L. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancerClin. Cancer Res.20061220 Pt 16106611510.1158/1078‑0432.CCR‑06‑1183
     [Google Scholar]
  75. AithalA. RauthS. KshirsagarP. ShahA. LakshmananI. JunkerW.M. JainM. PonnusamyM.P. BatraS.K. MUC16 as a novel target for cancer therapy.Expert Opin. Ther. Targets201822867568610.1080/14728222.2018.149884529999426
     [Google Scholar]
  76. HassanR. BeraT. PastanI. Mesothelin: A new target for immunotherapyCli. Cancer Res.20041012 Pt 13937394210.1158/1078‑0432.CCR‑03‑0801
     [Google Scholar]
  77. MorelloA. SadelainM. AdusumilliP.S. Mesothelin-targeted CARs: Driving T cells to solid tumors.Cancer Discov.20166213314610.1158/2159‑8290.CD‑15‑058326503962
     [Google Scholar]
  78. Mohabati MobarezA. SoleimaniN. EsmaeiliS.A. FarhangiB. Nanoparticle-based immunotherapy of breast cancer using recombinant Helicobacter pylori proteins.Eur. J. Pharm. Biopharm.2020155697610.1016/j.ejpb.2020.08.01332798667
     [Google Scholar]
  79. MausM.V. HaasA.R. BeattyG.L. AlbeldaS.M. LevineB.L. LiuX. ZhaoY. KalosM. JuneC.H. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans.Cancer Immunol. Res.201311263110.1158/2326‑6066.CIR‑13‑000624777247
     [Google Scholar]
  80. HaasA.R. TanyiJ.L. O'HaraM.H. Phase I study of lentiviral- transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers.Mol. Ther.201927111919192910.1016/j.ymthe.2019.07.015
     [Google Scholar]
  81. AdusumilliP.S. ZaudererM.G. RivièreI. SolomonS.B. RuschV.W. O’CearbhaillR.E. ZhuA. CheemaW. ChintalaN.K. HaltonE. PinedaJ. Perez-JohnstonR. TanK.S. DalyB. Araujo FilhoJ.A. NgaiD. McGeeE. VincentA. DiamonteC. SauterJ.L. ModiS. SikderD. SenechalB. WangX. TravisW.D. GönenM. RudinC.M. BrentjensR.J. JonesD.R. SadelainM. A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab.Cancer Discov.202111112748276310.1158/2159‑8290.CD‑21‑040734266984
     [Google Scholar]
  82. WangZ. LiN. FengK. ChenM. ZhangY. LiuY. YangQ. NieJ. TangN. ZhangX. ChengC. ShenL. HeJ. YeX. CaoW. WangH. HanW. Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors.Cell. Mol. Immunol.20211892188219810.1038/s41423‑021‑00749‑x34381179
     [Google Scholar]
  83. HassanR. ButlerM. O'CearbhaillR.E. Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: Phase 1/2 trial interim results.Nat. Med.20232982099210910.1038/s41591‑023‑02452‑y
     [Google Scholar]
  84. MaalejK.M. MerhiM. InchakalodyV.P. MestiriS. AlamM. MaccalliC. CherifH. UddinS. SteinhoffM. MarincolaF.M. DermimeS. CAR-cell therapy in the era of solid tumor treatment: Current challenges and emerging therapeutic advances.Mol. Cancer20232212010.1186/s12943‑023‑01723‑z36717905
     [Google Scholar]
  85. ShiD. ShiY. KasebA.O. QiX. ZhangY. ChiJ. LuQ. GaoH. JiangH. WangH. YuanD. MaH. WangH. LiZ. ZhaiB. Chimeric antigen receptor-glypican-3 T-cell therapy for advanced hepatocellular carcinoma: Results of phase I trials.Clin. Cancer Res.202026153979398910.1158/1078‑0432.CCR‑19‑325932371538
     [Google Scholar]
  86. GuoJ. TangQ. Recent updates on chimeric antigen receptor T cell therapy for hepatocellular carcinoma.Cancer Gene Ther.20212810-111075108710.1038/s41417‑020‑00259‑433500535
     [Google Scholar]
  87. WangY. ChenM. WuZ. TongC. DaiH. GuoY. LiuY. HuangJ. LvH. LuoC. FengK. YangQ. LiX. HanW. CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial.OncoImmunology201877e144016910.1080/2162402X.2018.144016929900044
     [Google Scholar]
  88. PatelU. AbernathyJ. SavaniB N. OluwoleO. SengsayadethS. DholariaB. CAR T cell therapy in solid tumors: A review of current clinical trials. EJHaem20223Suppl 1243110.1002/jha2.356
     [Google Scholar]
  89. PariziP.K. YarahmadiF. TabarH.M. HosseiniZ. SarliA. KiaN. TafazoliA. EsmaeiliS.A. MicroRNAs and target molecules in bladder cancer.Med. Oncol.2020371211810.1007/s12032‑020‑01435‑033216248
     [Google Scholar]
  90. QiC. ZhangP. LiuC. ZhangJ. ZhouJ. YuanJ. LiuD. ZhangM. GongJ. WangX. LiJ. ZhangX. LiN. PengX. LiuZ. YuanD. BaffaR. WangY. ShenL. Safety and efficacy of CT041 in patients with refractory metastatic pancreatic cancer: A pooled analysis of two early-phase trials.J. Clin. Oncol.202442212565257710.1200/JCO.23.0231438788174
     [Google Scholar]
  91. LouisC.U. SavoldoB. DottiG. PuleM. YvonE. MyersG.D. RossigC. RussellH.V. DioufO. LiuE. LiuH. WuM.F. GeeA.P. MeiZ. RooneyC.M. HeslopH.E. BrennerM.K. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma.Blood2011118236050605610.1182/blood‑2011‑05‑35444921984804
     [Google Scholar]
  92. HaffnerM.C. KronbergerI.E. RossJ.S. SheehanC.E. ZittM. MühlmannG. ÖfnerD. ZelgerB. EnsingerC. YangX.J. GeleyS. MargreiterR. BanderN.H. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers.Hum. Pathol.200940121754176110.1016/j.humpath.2009.06.00319716160
     [Google Scholar]
  93. EsmaeiliS-A. NejatollahiF. SahebkarA. Inhibition of intercellular communication between prostate cancer cells by a specific Anti-STEAP-1 single chain antibody.Anticancer Agents Med. Chem.201818121674167910.2174/187152061866617120809211529219059
     [Google Scholar]
  94. BilusicM. MadanR.A. GulleyJ.L. Immunotherapy of prostate cancer: Facts and hopes.Clin. Cancer Res.201723226764677010.1158/1078‑0432.CCR‑17‑001928663235
     [Google Scholar]
  95. JunghansR.P. MaQ. RathoreR. GomesE.M. BaisA.J. LoA.S.Y. AbediM. DaviesR.A. CabralH.J. Al-HomsiA.S. CohenS.I. Phase I trial of anti-PSMA designer CAR-T cells in prostate cancer: Possible role for interacting interleukin 2-T cell pharmacodynamics as a determinant of clinical response.Prostate201676141257127010.1002/pros.2321427324746
     [Google Scholar]
  96. MoonE.K. WangL.C.S. BekdacheK. LynnR.C. LoA. ThorneS.H. AlbeldaS.M. Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines.OncoImmunology201873e139599710.1080/2162402X.2017.139599729399394
     [Google Scholar]
  97. NishioN. DiaconuI. LiuH. CerulloV. CaruanaI. HoyosV. Bouchier-HayesL. SavoldoB. DottiG. Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors.Cancer Res.201474185195520510.1158/0008‑5472.CAN‑14‑069725060519
     [Google Scholar]
  98. HongM. PuauxA.L. HuangC. LoumagneL. TowC. MackayC. KatoM. Prévost-BlondelA. AvrilM.F. NardinA. AbastadoJ.P. Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control.Cancer Res.201171226997700910.1158/0008‑5472.CAN‑11‑146621948969
     [Google Scholar]
  99. KanagawaN. NiwaM. HatanakaY. TaniY. NakagawaS. FujitaT. YamamotoA. OkadaN. CC-chemokine ligand 17 gene therapy induces tumor regression through augmentation of tumor-infiltrating immune cells in a murine model of preexisting CT26 colon carcinoma.Int. J. Cancer200712192013202210.1002/ijc.2290817621629
     [Google Scholar]
  100. TchouJ. ZhaoY. LevineB.L. ZhangP.J. DavisM.M. MelenhorstJ.J. KulikovskayaI. BrennanA.L. LiuX. LaceyS.F. PoseyA.D. WilliamsA.D. SoA. Conejo-GarciaJ.R. PlesaG. YoungR.M. McGettiganS. CampbellJ. PierceR.H. MatroJ.M. DeMicheleA.M. ClarkA.S. CooperL.J. SchuchterL.M. VonderheideR.H. JuneC.H. Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer.Cancer Immunol. Res.20175121152116110.1158/2326‑6066.CIR‑17‑018929109077
     [Google Scholar]
  101. JinL. TaoH. KarachiA. LongY. HouA.Y. NaM. DysonK.A. GrippinA.J. DeleyrolleL.P. ZhangW. RajonD.A. WangQ.J. YangJ.C. KresakJ.L. SayourE.J. RahmanM. BovaF.J. LinZ. MitchellD.A. HuangJ. CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors.Nat. Commun.2019101401610.1038/s41467‑019‑11869‑431488817
     [Google Scholar]
  102. WhildingL. HalimL. DraperB. Parente-PereiraA. ZabinskiT. DaviesD. MaherJ. CAR T-cells targeting the integrin αvβ6 and co-expressing the chemokine receptor CXCR2 demonstrate enhanced homing and efficacy against several solid malignancies.Cancers (Basel)201911567410.3390/cancers1105067431091832
     [Google Scholar]
  103. CaruanaI. SavoldoB. HoyosV. WeberG. LiuH. KimE.S. IttmannM.M. MarchettiD. DottiG. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes.Nat. Med.201521552452910.1038/nm.383325849134
     [Google Scholar]
  104. WangL.C.S. LoA. SchollerJ. SunJ. MajumdarR.S. KapoorV. AntzisM. CotnerC.E. JohnsonL.A. DurhamA.C. SolomidesC.C. JuneC.H. PuréE. AlbeldaS.M. Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity.Cancer Immunol. Res.20142215416610.1158/2326‑6066.CIR‑13‑002724778279
     [Google Scholar]
  105. SacksteinR. The first step in adoptive cell immunotherapeutics: Assuring cell delivery via glycoengineering.Front. Immunol.20199308410.3389/fimmu.2018.0308430687313
     [Google Scholar]
  106. DengC. ZhaoJ. ZhouS. DongJ. CaoJ. GaoJ. BaiY. DengH. The vascular disrupting agent CA4P improves the antitumor efficacy of CAR-T cells in preclinical models of solid human tumors.Mol. Ther.2020281758810.1016/j.ymthe.2019.10.01031672285
     [Google Scholar]
  107. WangW. Marín-RamosN.I. HeH. ZengS. ChoH.Y. SwensonS.D. ZhengL. EpsteinA.L. SchönthalA.H. HofmanF.M. ChenL. ChenT.C. NEO100 enables brain delivery of blood‒brain barrier impermeable therapeutics.Neuro-Oncol.2021231637510.1093/neuonc/noaa20632877532
     [Google Scholar]
  108. ChinnasamyD. YuZ. KerkarS.P. ZhangL. MorganR.A. RestifoN.P. RosenbergS.A. Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice.Clin. Cancer Res.20121861672168310.1158/1078‑0432.CCR‑11‑305022291136
     [Google Scholar]
  109. FuX. RiveraA. TaoL. ZhangX. Genetically modified T cells targeting neovasculature efficiently destroy tumor blood vessels, shrink established solid tumors and increase nanoparticle delivery.Int. J. Cancer2013133102483249210.1002/ijc.2826923661285
     [Google Scholar]
  110. JuilleratA. MarechalA. FilholJ.M. ValogneY. ValtonJ. DuclertA. DuchateauP. PoirotL. An oxygen sensitive self-decision making engineered CAR T-cell.Sci. Rep.2017713983310.1038/srep3983328106050
     [Google Scholar]
  111. KostiP. OpzoomerJ.W. Larios-MartinezK.I. Henley-SmithR. ScudamoreC.L. OkesolaM. TaherM.Y.M. DaviesD.M. MuliaditanT. Larcombe-YoungD. WoodmanN. GillettC.E. ThavarajS. MaherJ. ArnoldJ.N. Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors.Cell Rep. Med.20212410022710.1016/j.xcrm.2021.10022733948568
     [Google Scholar]
  112. LiaoQ. HeH. MaoY. DingX. ZhangX. XuJ. Engineering T cells with hypoxia-inducible chimeric antigen receptor (HiCAR) for selective tumor killing.Biomark. Res.2020815610.1186/s40364‑020‑00238‑933292642
     [Google Scholar]
  113. NewickK. O’BrienS. SunJ. KapoorV. MaceykoS. LoA. PuréE. MoonE. AlbeldaS.M. Augmentation of CAR T-cell trafficking and antitumor efficacy by blocking protein kinase A localization.Cancer Immunol. Res.20164654155110.1158/2326‑6066.CIR‑15‑026327045023
     [Google Scholar]
  114. TangJ. ZouY. LiL. LuF. XuH. RenP. BaiF. NiedermannG. ZhuX. BAY 60-6583 enhances the antitumor function of chimeric antigen receptor-modified T cells independent of the adenosine A2b receptor.Front. Pharmacol.20211261980010.3389/fphar.2021.61980033776765
     [Google Scholar]
  115. LigtenbergM.A. MougiakakosD. MukhopadhyayM. WittK. LladserA. ChmielewskiM. RietT. AbkenH. KiesslingR. Coexpressed catalase protects chimeric antigen receptor-redirected T cells as well as bystander cells from oxidative stress-induced loss of antitumor activity.J. Immunol.2016196275976610.4049/jimmunol.140171026673145
     [Google Scholar]
  116. ManeM.M. CohenI.J. AckerstaffE. ShalabyK. IjomaJ.N. KoM. MaedaM. AlbegA.S. VemuriK. SatagopanJ. MorozA. ZuritaJ. ShenkerL. ShindoM. NicklesT. NikolovE. MorozM.A. KoutcherJ.A. SerganovaI. PonomarevV. BlasbergR.G. Lactate dehydrogenase a depletion alters MyC-CaP tumor metabolism, microenvironment, and CAR T cell therapy.Mol. Ther. Oncolytics20201838239510.1016/j.omto.2020.07.00632913888
     [Google Scholar]
  117. SuarezE.R. ChangD.K. SunJ. SuiJ. FreemanG.J. SignorettiS. ZhuQ. MarascoW.A. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model.Oncotarget2016723343413435510.18632/oncotarget.911427145284
     [Google Scholar]
  118. JungI.Y. KimY.Y. YuH.S. LeeM. KimS. LeeJ. CRISPR/Cas9- mediated knockout of DGK improves antitumor activities of human T cells.Cancer Res.201878164692470310.1158/0008‑5472.CAN‑18‑003029967261
     [Google Scholar]
  119. MarchesiF. VignaliD. ManiniB. RigamontiA. MontiP. Manipulation of glucose availability to boost cancer immunotherapies.Cancers (Basel)20201210294010.3390/cancers1210294033053779
     [Google Scholar]
  120. LongA.H. HasoW.M. ShernJ.F. WanhainenK.M. MurgaiM. IngaramoM. SmithJ.P. WalkerA.J. KohlerM.E. VenkateshwaraV.R. KaplanR.N. PattersonG.H. FryT.J. OrentasR.J. MackallC.L. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors.Nat. Med.201521658159010.1038/nm.383825939063
     [Google Scholar]
  121. WatanabeN. BajgainP. SukumaranS. AnsariS. HeslopH.E. RooneyC.M. BrennerM.K. LeenA.M. VeraJ.F. Fine-tuning the CAR spacer improves T-cell potency.OncoImmunology2016512e125365610.1080/2162402X.2016.125365628180032
     [Google Scholar]
  122. CherkasskyL. MorelloA. Villena-VargasJ. FengY. DimitrovD.S. JonesD.R. SadelainM. AdusumilliP.S. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition.J. Clin. Invest.201612683130314410.1172/JCI8309227454297
     [Google Scholar]
  123. LiuX. RanganathanR. JiangS. FangC. SunJ. KimS. NewickK. LoA. JuneC.H. ZhaoY. MoonE.K. A chimeric switch-receptor targeting PD1 augments the efficacy of second-generation CAR T cells in advanced solid tumors.Cancer Res.20167661578159010.1158/0008‑5472.CAN‑15‑252426979791
     [Google Scholar]
  124. BaileyS.R. MausM.V. Gene editing for immune cell therapies.Nat. Biotechnol.201937121425143410.1038/s41587‑019‑0137‑831160723
     [Google Scholar]
  125. ChoiB.D. YuX. CastanoA.P. BouffardA.A. SchmidtsA. LarsonR.C. BaileyS.R. BoroughsA.C. FrigaultM.J. LeickM.B. ScarfòI. CetruloC.L. DemehriS. NahedB.V. CahillD.P. WakimotoH. CurryW.T. CarterB.S. MausM.V. CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity.Nat. Biotechnol.20193791049105810.1038/s41587‑019‑0192‑131332324
     [Google Scholar]
  126. LohmuellerJ.J. HamJ.D. KvorjakM. FinnO.J. mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting.OncoImmunology201871e136860410.1080/2162402X.2017.136860429296519
     [Google Scholar]
  127. UrbanskaK. LanitisE. PoussinM. LynnR.C. GavinB.P. KeldermanS. YuJ. SchollerN. PowellD.J. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor.Cancer Res.20127271844185210.1158/0008‑5472.CAN‑11‑389022315351
     [Google Scholar]
  128. ChoJ.H. CollinsJ.J. WongW.W. Universal chimeric antigen receptors for multiplexed and logical control of T cell responses.Cell2018173614261438.e1110.1016/j.cell.2018.03.03829706540
     [Google Scholar]
  129. WilkieS. BurbridgeS.E. Chiapero-StankeL. PereiraA.C.P. ClearyS. van der StegenS.J.C. SpicerJ.F. DaviesD.M. MaherJ. Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4.J. Biol. Chem.201028533255382554410.1074/jbc.M110.12795120562098
     [Google Scholar]
  130. KoneruM. PurdonT.J. SpriggsD. KoneruS. BrentjensR.J. IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo.OncoImmunology201543e99444610.4161/2162402X.2014.99444625949921
     [Google Scholar]
  131. MohammedS. SukumaranS. BajgainP. Improving chimeric antigen receptor-modified T cell function by reversing the immunosuppressive tumor microenvironment of pancreatic cancer.Mol. Ther.201725124925810.1016/j.ymthe.2016.10.016
     [Google Scholar]
  132. BecerraC.R. ManjiG.A. KimD.W. GardnerO. MalankarA. ShawJ. BlassD. YiX. FosterA.E. WoodardP. Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results with cyclophosphamide (Cy) ± fludarabine (Flu) lymphodepletion (LD).J. Clin. Oncol.201937Suppl 152536253610.1200/JCO.2019.37.15_suppl.2536
     [Google Scholar]
  133. HegdeM. DeRenzoC.C. ZhangH. MataM. GerkenC. ShreeA. YiZ. BrawleyV. DakhovaO. WuM-F. LiuH. HicksJ. GrilleyB. GeeA.P. RooneyC.M. BrennerM.K. HeslopH.E. WelsW. GottschalkS. AhmedN.M. Expansion of HER2- CAR T cells after lymphodepletion and clinical responses in patients with advanced sarcoma.J. Clin. Oncol.201735Suppl 151050810.1200/JCO.2017.35.15_suppl.10508
     [Google Scholar]
  134. ShahverdiM. HajiasgharzadehK. SorkhabiA.D. The regulatory role of autophagy-related miRNAs in lung cancer drug resistance. Biomed. Pharmacother.202214811273510.1016/j.biopha.2022.112735
     [Google Scholar]
  135. WangZ. WuZ. LiuY. HanW. New development in CAR-T cell therapy.J. Hematol. Oncol.20171015310.1186/s13045‑017‑0423‑128222796
     [Google Scholar]
  136. HegdeM. MukherjeeM. GradaZ. PignataA. LandiD. NavaiS.A. WakefieldA. FousekK. BielamowiczK. ChowK.K.H. BrawleyV.S. ByrdT.T. KrebsS. GottschalkS. WelsW.S. BakerM.L. DottiG. MamonkinM. BrennerM.K. OrangeJ.S. AhmedN. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape.J. Clin. Invest.201612683036305210.1172/JCI8341627427982
     [Google Scholar]
  137. FedorovV.D. ThemeliM. SadelainM. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses.Sci. Transl. Med.20135215215ra17210.1126/scitranslmed.300659724337479
     [Google Scholar]
  138. DiaconuI. BallardB. ZhangM. Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cellsMol. Ther.201725358059210.1016/j.ymthe.2017.01.011
     [Google Scholar]
  139. GargettT. BrownM.P. The inducible caspase-9 suicide gene system as a safety switch to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells.Front. Pharmacol.2014523510.3389/fphar.2014.0023525389405
     [Google Scholar]
  140. SentmanC.L. MeehanK.R. NKG2D CARs as cell therapy for cancer.Cancer J.201420215615910.1097/PPO.000000000000002924667963
     [Google Scholar]
  141. ZhangT. BarberA. SentmanC.L. Chimeric NKG2D modified T cells inhibit systemic T-cell lymphoma growth in a manner involving multiple cytokines and cytotoxic pathways.Cancer Res.20076722110291103610.1158/0008‑5472.CAN‑07‑225118006849
     [Google Scholar]
  142. ChmielewskiM. AbkenH. TRUCKs: The fourth generation of CARs.Expert Opin. Biol. Ther.20151581145115410.1517/14712598.2015.104643025985798
     [Google Scholar]
  143. ChinnasamyD. YuZ. TheoretM.R. ZhaoY. ShrimaliR.K. MorganR.A. FeldmanS.A. RestifoN.P. RosenbergS.A. Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice.J. Clin. Invest.2010120113953396810.1172/JCI4349020978347
     [Google Scholar]
  144. JuneC.H. O’ConnorR.S. KawalekarO.U. GhassemiS. MiloneM.C. CAR T cell immunotherapy for human cancer.Science201835963821361136510.1126/science.aar671129567707
     [Google Scholar]
  145. PotezM. SnedalS. SheC. Use of phage display biopanning as a tool to design CAR-T cells against glioma stem cellsFront. Oncol.202313112427210.3389/fonc.2023.1124272
     [Google Scholar]
  146. YangF. ZhangF. JiF. ChenJ. LiJ. ChenZ. HuZ. GuoZ. Self-delivery of TIGIT-blocking scFv enhances CAR-T immunotherapy in solid tumors.Front. Immunol.202314117592010.3389/fimmu.2023.117592037359558
     [Google Scholar]
  147. SwanS.L. MehtaN. IlichE. ShenS.H. WilkinsonD.S. AndersonA.R. SeguraT. Sanchez-PerezL. SampsonJ.H. BellamkondaR.V. IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma.Front. Immunol.202314108554710.3389/fimmu.2023.108554736817432
     [Google Scholar]
  148. SuntharalingamG. PerryM.R. WardS. BrettS.J. Castello-CortesA. BrunnerM.D. PanoskaltsisN. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412.N. Engl. J. Med.2006355101018102810.1056/NEJMoa06384216908486
     [Google Scholar]
  149. TeacheyD.T. LaceyS.F. ShawP.A. MelenhorstJ.J. MaudeS.L. FreyN. PequignotE. GonzalezV.E. ChenF. FinklesteinJ. BarrettD.M. WeissS.L. FitzgeraldJ.C. BergR.A. AplencR. CallahanC. RheingoldS.R. ZhengZ. Rose-JohnS. WhiteJ.C. NazimuddinF. WertheimG. LevineB.L. JuneC.H. PorterD.L. GruppS.A. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia.Cancer Discov.20166666467910.1158/2159‑8290.CD‑16‑004027076371
     [Google Scholar]
  150. LeeD.W. GardnerR. PorterD.L. LouisC.U. AhmedN. JensenM. GruppS.A. MackallC.L. Current concepts in the diagnosis and management of cytokine release syndrome.Blood2014124218819510.1182/blood‑2014‑05‑55272924876563
     [Google Scholar]
  151. MiloneM.C. BhojV.G. The pharmacology of T cell therapies.Mol. Ther. Methods Clin. Dev.2018821022110.1016/j.omtm.2018.01.01029552577
     [Google Scholar]
  152. MessmerA.S. QueY.A. SchankinC. BanzY. BacherU. NovakU. PabstT. CAR T-cell therapy and critical care.Wien. Klin. Wochenschr.202113323-241318132510.1007/s00508‑021‑01948‑234613477
     [Google Scholar]
  153. MurthyH.S. YassineF. IqbalM. AlotaibiS. MoustafaM.A. Kharfan-DabajaM.A. Management of CAR T-cell related toxicities: What did the learning curve teach us so far?Hematol. Oncol. Stem Cell Ther.202215310011110.56875/2589‑0646.102936395496
     [Google Scholar]
  154. JainT. OlsonT.S. LockeF.L. How I treat cytopenias after CAR T- cell therapy.Blood202314120blood.202201741510.1182/blood.202201741536800563
     [Google Scholar]
  155. StewartA.G. HendenA.S. Infectious complications of CAR T-cell therapy: A clinical update.Ther. Adv. Infect. Dis.202182049936121103677310.1177/2049936121103677334457269
     [Google Scholar]
  156. MohammadiS. AbdollahiE. NezamniaM. Adoptive transfer of Tregs: A novel strategy for cell-based immunotherapy in spontaneous abortion: Lessons from experimental models. Int. Immunopharmacol.20219010719510.1016/j.intimp.2020.107195
     [Google Scholar]
  157. DasyamN. GeorgeP. WeinkoveR. Chimeric antigen receptor T- cell therapies: Optimising the dose.Br. J. Clin. Pharmacol.20208691678168910.1111/bcp.1428132175617
     [Google Scholar]
  158. MitchellE. VassiliouG.S. T-cell cancer after CAR T-cell therapy.N. Engl. J. Med.2024390222120212110.1056/NEJMe240553838865665
     [Google Scholar]
  159. HamiltonM.P. SugioT. NoordenbosT. ShiS. BulterysP.L. LiuC.L. KangX. OlsenM.N. GoodZ. DahiyaS. FrankM.J. SahafB. MackallC.L. GratzingerD. DiehnM. AlizadehA.A. MiklosD.B. Risk of second tumors and T-cell lymphoma after CAR T-cell therapy.N. Engl. J. Med.2024390222047206010.1056/NEJMoa240136138865660
     [Google Scholar]
  160. OzdemirliM. LoughneyT.M. DenizE. ChahineJ.J. AlbitarM. PittalugaS. SadighS. ArmandP. UrenA. AndersonK.C. Indolent CD4+ CAR T-cell lymphoma after cilta-cel CAR T-cell therapy.N. Engl. J. Med.2024390222074208210.1056/NEJMoa240153038865661
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128336391241107112957
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Revolutionizing Cancer Treatment: Unveiling the Power of CAR T-cell Therapy
Curr. Pharm. Des. 31, 1020 (2025); https://doi.org/10.2174/0113816128336391241107112957
/content/journals/cpd/10.2174/0113816128336391241107112957
/content/journals/cpd/10.2174/0113816128336391241107112957
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  • Article Type:     Review Article
Keyword(s): Cancer treatment; CAR T-cell; immunotherapy; malignancy; oncology; tumour

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