Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Design
  4. Fast Track Articles
  5. Fast Track Article
image of Revolutionizing Cancer Treatment: Unveiling the Power of CAR T-cell Therapy

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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128336391241107112957
2025-01-02
2025-01-30

  • From This Site

    /content/journals/cpd/10.2174/0113816128336391241107112957
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Mattiuzzi C. Lippi G. Current Cancer Epidemiology. J. Epidemiol. Glob. Health 2019 9 4 217 222 10.2991/jegh.k.191008.001 31854162
    [Google Scholar]
  2. Sharma P. Jhawat V. Mathur P. Dutt R. Innovation in cancer therapeutics and regulatory perspectives. Med. Oncol. 239 5 76 2022 10.1007/s12032‑022‑01677‑0 35195787
    [Google Scholar]
  3. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 71 3 209 249 10.3322/caac.21660 33538338
    [Google Scholar]
  4. Sterner R.C. Sterner R.M. CAR-T cell therapy: Current limitations and potential strategies. Blood Cancer J. 11 4 69 2021 10.1038/s41408‑021‑00459‑7 33824268
    [Google Scholar]
  5. Waldman A.D. Fritz J.M. Lenardo M.J. Nat. Rev. Immunol. A guide to cancer immunotherapy: From T cell basic science to clinical practice. 20 11 651 668 2020 10.1038/s41577‑020‑0306‑5 32433532
    [Google Scholar]
  6. Keyvani V. Riahi E. Yousefi M. Esmaeili S.A. Shafabakhsh R. Moradi Hasan-Abad A. Mahjoubin-Tehran M. Hamblin M.R. Mollazadeh S. Mirzaei H. Gynecologic cancer, cancer stem cells, and possible targeted therapies. Front. Pharmacol. 2022 13 823572 10.3389/fphar.2022.823572 35250573
    [Google Scholar]
  7. Garrido F. Aptsiauri N. Doorduijn E.M. Garcia Lora A.M. van Hall T. The urgent need to recover MHC class I in cancers for effective immunotherapy. Curr. Opin. Immunol. 2016 39 44 51 10.1016/j.coi.2015.12.007 26796069
    [Google Scholar]
  8. Kuwana Y. Asakura Y. Utsunomiya N. Nakanishi M. Arata Y. Itoh S. Nagase F. Kurosawa Y. Expression of chimeric receptor composed of immunoglobulin-derived V resions and T-cell receptor-derived C regions. Biochem. Biophys. Res. Commun. 1987 149 3 960 968 10.1016/0006‑291X(87)90502‑X 3122749
    [Google Scholar]
  9. Brudno J.N. Kochenderfer J.N. Toxicities of chimeric antigen receptor T cells: Recognition and management. Blood 2016 127 26 3321 3330 10.1182/blood‑2016‑04‑703751 27207799
    [Google Scholar]
  10. Grupp S.A. Kalos M. Barrett D. Aplenc R. Porter D.L. Rheingold S.R. Teachey D.T. Chew A. Hauck B. Wright J.F. Milone M.C. Levine B.L. June C.H. Chimeric antigen receptor- modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 2013 368 16 1509 1518 10.1056/NEJMoa1215134 23527958
    [Google Scholar]
  11. Neelapu S.S. Tummala S. Kebriaei P. Wierda W. Gutierrez C. Locke F.L. Komanduri K.V. Lin Y. Jain N. Daver N. Westin J. Gulbis A.M. Loghin M.E. de Groot J.F. Adkins S. Davis S.E. Rezvani K. Hwu P. Shpall E.J. Chimeric antigen receptor T-cell therapy - Assessment and management of toxicities. Nat. Rev. Clin. Oncol. 2018 15 1 47 62 10.1038/nrclinonc.2017.148 28925994
    [Google Scholar]
  12. Hernandez I. Prasad V. Gellad W.F. Total costs of chimeric antigen receptor T-cell immunotherapy. JAMA Oncol. 2018 4 7 994 996 10.1001/jamaoncol.2018.0977 29710129
    [Google Scholar]
  13. Vormittag P. Gunn R. Ghorashian S. Veraitch F.S. A guide to manufacturing CAR T cell therapies. Curr. Opin. Biotechnol. 2018 53 164 181 10.1016/j.copbio.2018.01.025 29462761
    [Google Scholar]
  14. Brentjens R.J. Davila M.L. Riviere I. CD19-targeted T Cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci. Transl. Med. 5 177 177ra38 2013 10.1126/scitranslmed.3005930
    [Google Scholar]
  15. Cohen A.D. Garfall A.L. Stadtmauer E.A. Melenhorst J.J. Lacey S.F. Lancaster E. Vogl D.T. Weiss B.M. Dengel K. Nelson A. Plesa G. Chen F. Davis M.M. Hwang W.T. Young R.M. Brogdon J.L. Isaacs R. Pruteanu-Malinici I. Siegel D.L. Levine B.L. June C.H. Milone M.C. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J. Clin. Invest. 2019 129 6 2210 2221 10.1172/JCI126397 30896447
    [Google Scholar]
  16. Koneru M. O’Cearbhaill R. Pendharkar S. Spriggs D.R. Brentjens R.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. 2015 13 1 102 10.1186/s12967‑015‑0460‑x 25890361
    [Google Scholar]
  17. Majzner R.G. Theruvath J.L. Nellan A. Heitzeneder S. Cui Y. Mount C.W. Rietberg S.P. Linde M.H. Xu P. Rota C. Sotillo E. Labanieh L. Lee D.W. Orentas R.J. Dimitrov D.S. Zhu Z. Croix B.S. Delaidelli A. Sekunova A. Bonvini E. Mitra S.S. Quezado M.M. Majeti R. Monje M. Sorensen P.H.B. Maris J.M. Mackall C.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. 2019 25 8 2560 2574 10.1158/1078‑0432.CCR‑18‑0432 30655315
    [Google Scholar]
  18. Neelapu S.S. Locke F.L. Bartlett N.L. Lekakis L.J. Miklos D.B. Jacobson C.A. Braunschweig I. Oluwole O.O. Siddiqi T. Lin Y. Timmerman J.M. Stiff P.J. Friedberg J.W. Flinn I.W. Goy A. Hill B.T. Smith M.R. Deol A. Farooq U. McSweeney P. Munoz J. Avivi I. Castro J.E. Westin J.R. Chavez J.C. Ghobadi A. Komanduri K.V. Levy R. Jacobsen E.D. Witzig T.E. Reagan P. Bot A. Rossi J. Navale L. Jiang Y. Aycock J. Elias M. Chang D. Wiezorek J. Go W.Y. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N. Engl. J. Med. 2017 377 26 2531 2544 10.1056/NEJMoa1707447 29226797
    [Google Scholar]
  19. Porter D.L. Levine B.L. Kalos M. Bagg A. June C.H. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 2011 365 8 725 733 10.1056/NEJMoa1103849 21830940
    [Google Scholar]
  20. Raje N. Berdeja J. Lin Y. Siegel D. Jagannath S. Madduri D. Liedtke M. Rosenblatt J. Maus M.V. Turka A. Lam L.P. Morgan R.A. Friedman K. Massaro M. Wang J. Russotti G. Yang Z. Campbell T. Hege K. Petrocca F. Quigley M.T. Munshi N. Kochenderfer J.N. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N. Engl. J. Med. 2019 380 18 1726 1737 10.1056/NEJMoa1817226 31042825
    [Google Scholar]
  21. van Schalkwyk M.C.I. Papa S.E. Jeannon J.P. Urbano T.G. Spicer J.F. Maher J. 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. 2013 24 3 134 142 10.1089/humc.2013.144 24099518
    [Google Scholar]
  22. Yeku O.O. Purdon T.J. Koneru M. Spriggs D. Brentjens R.J. Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment. Sci. Rep. 2017 7 1 10541 10.1038/s41598‑017‑10940‑8 28874817
    [Google Scholar]
  23. Atabati H. Yazdanpanah E. Mortazavi H. bajestani S.G. Raoofi A. Esmaeili S.A. Khaledi A. Saburi E. Afshari J.T. Sathyapalan T. Moghaddam A.S. Sahebkar A. Immunoregulatory effects of tolerogenic probiotics in multiple sclerosis. Adv. Exp. Med. Biol. 2021 1286 Part II 87 105 10.1007/978‑3‑030‑55035‑6_6 33725347
    [Google Scholar]
  24. Gross G. Waks T. Eshhar Z. Expression of immunoglobulin-T- cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc. Natl. Acad. Sci. USA 1989 86 24 10024 10028 10.1073/pnas.86.24.10024 2513569
    [Google Scholar]
  25. Eshhar Z. Waks T. Gross G. Schindler D.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. USA 1993 90 2 720 724 10.1073/pnas.90.2.720 8421711
    [Google Scholar]
  26. Bird R.E. Hardman K.D. Jacobson J.W. Johnson S. Kaufman B.M. Lee S.M. Lee T. Pope S.H. Riordan G.S. Whitlow M. Single-chain antigen-binding proteins. Science 1988 242 4877 423 426 10.1126/science.3140379 3140379
    [Google Scholar]
  27. Huston J.S. Levinson D. Mudgett-Hunter M. Tai M.S. Novotný J. Margolies M.N. Ridge R.J. Bruccoleri R.E. Haber E. Crea R. 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. USA 1988 85 16 5879 5883 10.1073/pnas.85.16.5879 3045807
    [Google Scholar]
  28. Eshhar Z. Tumor-specific T-bodies: Towards clinical application. Cancer Immunol. Immunother. 1997 45 3-4 131 136 10.1007/s002620050415 9435856
    [Google Scholar]
  29. Rosenbaum L. Tragedy, perseverance, and chance - The story of CAR-T therapy. N. Engl. J. Med. 2017 377 14 1313 1315 10.1056/NEJMp1711886 28902570
    [Google Scholar]
  30. Maude S.L. Frey N. Shaw P.A. Aplenc R. Barrett D.M. Bunin N.J. Chew A. Gonzalez V.E. Zheng Z. Lacey S.F. Mahnke Y.D. Melenhorst J.J. Rheingold S.R. Shen A. Teachey D.T. Levine B.L. June C.H. Porter D.L. Grupp S.A. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 2014 371 16 1507 1517 10.1056/NEJMoa1407222 25317870
    [Google Scholar]
  31. Maude S.L. Laetsch T.W. Buechner J. Rives S. Boyer M. Bittencourt H. Bader P. Verneris M.R. Stefanski H.E. Myers G.D. Qayed M. De Moerloose B. Hiramatsu H. Schlis K. Davis K.L. Martin P.L. Nemecek E.R. Yanik G.A. Peters C. Baruchel A. Boissel N. Mechinaud F. Balduzzi A. Krueger J. June C.H. Levine B.L. Wood P. Taran T. Leung M. Mueller K.T. Zhang Y. Sen K. Lebwohl D. Pulsipher M.A. Grupp S.A. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl. J. Med. 2018 378 5 439 448 10.1056/NEJMoa1709866 29385370
    [Google Scholar]
  32. Park J.H. Rivière I. Gonen M. Wang X. Sénéchal B. Curran K.J. Sauter C. Wang Y. Santomasso B. Mead E. Roshal M. Maslak P. Davila M. Brentjens R.J. Sadelain M. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N. Engl. J. Med. 2018 378 5 449 459 10.1056/NEJMoa1709919 29385376
    [Google Scholar]
  33. Porter D.L. Hwang W.-T. Frey N.V. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci. Transl. Med. 7 303 2015 10.1126/scitranslmed.aac5415
    [Google Scholar]
  34. Schuster S.J. Svoboda J. Chong E.A. Nasta S.D. Mato A.R. Anak Ö. Brogdon J.L. Pruteanu-Malinici I. Bhoj V. Landsburg D. Wasik M. Levine B.L. Lacey S.F. Melenhorst J.J. Porter D.L. June C.H. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N. Engl. J. Med. 2017 377 26 2545 2554 10.1056/NEJMoa1708566 29226764
    [Google Scholar]
  35. FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome. 2017 Available 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. 2018 Available 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. Schepisi G. Cursano M.C. Casadei C. Menna C. Altavilla A. Lolli C. Cerchione C. Paganelli G. Santini D. Tonini G. Martinelli G. De Giorgi U. CAR-T cell therapy: A potential new strategy against prostate cancer. J. Immunother. Cancer 2019 7 1 258 10.1186/s40425‑019‑0741‑7 31619289
    [Google Scholar]
  38. Ruiz-Garcia E. Astudillo-de la Vega H. Translational Research and Onco-Omics Applications in the Era of Cancer Personal Genomics. Springer Cham 2019 10.1007/978‑3‑030‑24100‑1
    [Google Scholar]
  39. Jensen M.C. Popplewell L. Cooper L.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. 2010 16 9 1245 1256 10.1016/j.bbmt.2010.03.014
    [Google Scholar]
  40. Thistlethwaite F.C. Gilham D.E. Guest R.D. Rothwell D.G. Pillai M. Burt D.J. Byatte A.J. Kirillova N. Valle J.W. Sharma S.K. Chester K.A. Westwood N.B. Halford S.E.R. Nabarro S. Wan S. Austin E. Hawkins R.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. 2017 66 11 1425 1436 10.1007/s00262‑017‑2034‑7 28660319
    [Google Scholar]
  41. Savoldo B. Ramos C.A. Liu E. Mims M.P. Keating M.J. Carrum G. Kamble R.T. Bollard C.M. Gee A.P. Mei Z. Liu H. Grilley B. Rooney C.M. Heslop H.E. Brenner M.K. Dotti G. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J. Clin. Invest. 2011 121 5 1822 1826 10.1172/JCI46110 21540550
    [Google Scholar]
  42. Zhong X.S. Matsushita M. Plotkin J. Riviere I. Sadelain M. 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. 2010 18 2 413 420 10.1038/mt.2009.210 19773745
    [Google Scholar]
  43. Chmielewski M. Abken H. TRUCKS, the fourth‐generation CAR T cells: Current developments and clinical translation. Adv. Cell Gene Ther. 2020 3 3 e84 10.1002/acg2.84
    [Google Scholar]
  44. Kagoya Y. Tanaka S. Guo T. Anczurowski M. Wang C.H. Saso K. Butler M.O. Minden M.D. Hirano N. A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects. Nat. Med. 2018 24 3 352 359 10.1038/nm.4478 29400710
    [Google Scholar]
  45. Honikel M.M. Olejniczak S.H. Co-stimulatory receptor signaling in CAR-T cells. Biomolecules 2022 12 9 1303 10.3390/biom12091303 36139142
    [Google Scholar]
  46. Park J.H. Riviere I. Wang X. Efficacy and safety of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed or refractory B-ALL. J. Clin. Oncol. 33 Suppl 15 2015 10.1200/jco.2015.33.15_suppl.7010
    [Google Scholar]
  47. Lee D.W. Kochenderfer J.N. Stetler-Stevenson M. Cui Y.K. Delbrook C. Feldman S.A. Fry T.J. Orentas R. Sabatino M. Shah N.N. Steinberg S.M. Stroncek D. Tschernia N. Yuan C. Zhang H. Zhang L. Rosenberg S.A. Wayne A.S. Mackall C.L. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial. Lancet 2015 385 9967 517 528 10.1016/S0140‑6736(14)61403‑3 25319501
    [Google Scholar]
  48. Shah N.N. Lee D.W. Yates B. Yuan C.M. Shalabi H. Martin S. Wolters P.L. Steinberg S.M. Baker E.H. Delbrook C.P. Stetler-Stevenson M. Fry T.J. Stroncek D.F. Mackall C.L. Long-term follow-up of CD19- CAR T-cell therapy in children and young adults with B-ALL. J. Clin. Oncol. 2021 39 15 1650 1659 10.1200/JCO.20.02262 33764809
    [Google Scholar]
  49. Turtle C.J. Hanafi L.A. Berger C. Gooley T.A. Cherian S. Hudecek M. Sommermeyer D. Melville K. Pender B. Budiarto T.M. Robinson E. Steevens N.N. Chaney C. Soma L. Chen X. Yeung C. Wood B. Li D. Cao J. Heimfeld S. Jensen M.C. Riddell S.R. Maloney D.G. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J. Clin. Invest. 2016 126 6 2123 2138 10.1172/JCI85309 27111235
    [Google Scholar]
  50. Sabatino M. Choi K. Chiruvolu V. Better M. 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). Blood 2016 128 22 1227 10.1182/blood.V128.22.1227.1227
    [Google Scholar]
  51. Shah B.D. Bishop M.R. Oluwole O.O. Logan A.C. Baer M.R. Donnellan W.B. O’Dwyer K.M. Holmes H. Arellano M.L. Ghobadi A. Pagel J.M. Lin Y. Cassaday R.D. Park J.H. Abedi M. Castro J.E. DeAngelo D.J. Malone A.K. Mawad R. Schiller G.J. Rossi J.M. Bot A. Shen T. Goyal L. Jain R.K. Vezan R. Wierda W.G. KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results. Blood 2021 138 1 11 22 10.1182/blood.2020009098 33827116
    [Google Scholar]
  52. Shah B.D. Ghobadi A. Oluwole O.O. Logan A.C. Boissel N. Cassaday R.D. Leguay T. Bishop M.R. Topp M.S. Tzachanis D. O’Dwyer K.M. Arellano M.L. Lin Y. Baer M.R. Schiller G.J. Park J.H. Subklewe M. Abedi M. Minnema M.C. Wierda W.G. DeAngelo D.J. Stiff P. Jeyakumar D. Feng C. Dong J. Shen T. Milletti F. Rossi J.M. Vezan R. Masouleh B.K. Houot R. 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. Lancet 2021 398 10299 491 502 10.1016/S0140‑6736(21)01222‑8 34097852
    [Google Scholar]
  53. Davila M.L. Sadelain M. Biology and clinical application of CAR T cells for B cell malignancies. Int. J. Hematol. 2016 104 1 6 17 10.1007/s12185‑016‑2039‑6 27262700
    [Google Scholar]
  54. Shalabi H. Angiolillo A. Fry T.J. Beyond CD19: Opportunities for future development of targeted immunotherapy in pediatric relapsed-refractory acute leukemia. Front Pediatr. 2015 3 80 10.3389/fped.2015.00080 26484338
    [Google Scholar]
  55. Burger J.A. Tedeschi A. Barr P.M. Robak T. Owen C. Ghia P. Bairey O. Hillmen P. Bartlett N.L. Li J. Simpson D. Grosicki S. Devereux S. McCarthy H. Coutre S. Quach H. Gaidano G. Maslyak Z. Stevens D.A. Janssens A. Offner F. Mayer J. O’Dwyer M. Hellmann A. Schuh A. Siddiqi T. Polliack A. Tam C.S. Suri D. Cheng M. Clow F. Styles L. James D.F. Kipps T.J. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N. Engl. J. Med. 2015 373 25 2425 2437 10.1056/NEJMoa1509388 26639149
    [Google Scholar]
  56. Turtle C.J. Hay K.A. Hanafi L.A. Li D. Cherian S. Chen X. Wood B. Lozanski A. Byrd J.C. Heimfeld S. Riddell S.R. Maloney D.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. 2017 35 26 3010 3020 10.1200/JCO.2017.72.8519 28715249
    [Google Scholar]
  57. Frey N.V. Gill S. Hexner E.O. Schuster S. Nasta S. Loren A. Svoboda J. Stadtmauer E. Landsburg D.J. Mato A. Levine B.L. Lacey S.F. Melenhorst J.J. Veloso E. Gaymon A. Pequignot E. Shan X. Hwang W.T. June C.H. Porter D.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. 2020 38 25 2862 2871 10.1200/JCO.19.03237 32298202
    [Google Scholar]
  58. Todorovic Z. Todorovic D. Markovic V. Ladjevac N. Zdravkovic N. Djurdjevic P. Arsenijevic N. Milovanovic M. Arsenijevic A. Milovanovic J. CAR T cell therapy for chronic lymphocytic leukemia: Successes and shortcomings. Curr. Oncol. 2022 29 5 3647 3657 10.3390/curroncol29050293 35621683
    [Google Scholar]
  59. Locke F.L. Miklos D.B. Jacobson C.A. Perales M.A. Kersten M.J. Oluwole O.O. Ghobadi A. Rapoport A.P. McGuirk J. Pagel J.M. Muñoz J. Farooq U. van Meerten T. Reagan P.M. Sureda A. Flinn I.W. Vandenberghe P. Song K.W. Dickinson M. Minnema M.C. Riedell P.A. Leslie L.A. Chaganti S. Yang Y. Filosto S. Shah J. Schupp M. To C. Cheng P. Gordon L.I. Westin J.R. Axicabtagene ciloleucel as second-line therapy for large B-Cell lymphoma. N. Engl. J. Med. 2022 386 7 640 654 10.1056/NEJMoa2116133 34891224
    [Google Scholar]
  60. Abramson J.S. Palomba M.L. Gordon L.I. Lunning M.A. Wang M. Arnason J. Mehta A. Purev E. Maloney D.G. Andreadis C. Sehgal A. Solomon S.R. Ghosh N. Albertson T.M. Garcia J. Kostic A. Mallaney M. Ogasawara K. Newhall K. Kim Y. Li D. Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet 2020 396 10254 839 852 10.1016/S0140‑6736(20)31366‑0 32888407
    [Google Scholar]
  61. Kamdar M. Solomon S.R. Arnason J. Johnston P.B. Glass B. Bachanova V. Ibrahimi S. Mielke S. Mutsaers P. Hernandez-Ilizaliturri F. Izutsu K. Morschhauser F. Lunning M. Maloney D.G. Crotta A. Montheard S. Previtali A. Stepan L. Ogasawara K. Mack T. Abramson J.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. Lancet 2022 399 10343 2294 2308 10.1016/S0140‑6736(22)00662‑6 35717989
    [Google Scholar]
  62. Schuster S.J. Tam C.S. Borchmann P. Worel N. McGuirk J.P. Holte H. Waller E.K. Jaglowski S. Bishop M.R. Damon L.E. Foley S.R. Westin J.R. Fleury I. Ho P.J. Mielke S. Teshima T. Janakiram M. Hsu J.M. Izutsu K. Kersten M.J. Ghosh M. Wagner-Johnston N. Kato K. Corradini P. Martinez-Prieto M. Han X. Tiwari R. Salles G. Maziarz R.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. 2021 22 10 1403 1415 10.1016/S1470‑2045(21)00375‑2 34516954
    [Google Scholar]
  63. Sehgal A. Hoda D. Riedell P.A. Ghosh N. Hamadani M. Hildebrandt G.C. Godwin J.E. Reagan P.M. Wagner-Johnston N. Essell J. Nath R. Solomon S.R. Champion R. Licitra E. Fanning S. Gupta N. Dubowy R. D’Andrea A. Wang L. Ogasawara K. Thorpe J. Gordon L.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. 2022 23 8 1066 1077 10.1016/S1470‑2045(22)00339‑4 35839786
    [Google Scholar]
  64. Garfall A.L. Maus M.V. Hwang W.T. Lacey S.F. Mahnke Y.D. Melenhorst J.J. Zheng Z. Vogl D.T. Cohen A.D. Weiss B.M. Dengel K. Kerr N.D.S. Bagg A. Levine B.L. June C.H. Stadtmauer E.A. Chimeric antigen receptor T cells against CD19 for multiple myeloma. N. Engl. J. Med. 2015 373 11 1040 1047 10.1056/NEJMoa1504542 26352815
    [Google Scholar]
  65. Scheller L. Tebuka E. Rambau P.F. BCMA CAR-T cells in multiple myeloma-ready for take-off? Leuk. Lymphoma 65 2 2024 143 157 10.1080/10428194.2023.2276676
    [Google Scholar]
  66. D’Aloia M.M. Zizzari I.G. Sacchetti B. Pierelli L. Alimandi M. CAR-T cells: The long and winding road to solid tumors. Cell Death Dis. 2018 9 3 282 10.1038/s41419‑018‑0278‑6 29449531
    [Google Scholar]
  67. Fiorentino A. Bonis P.D. Chiesa S. Balducci M. Fusco V. Elderly patients with glioblastoma: The treatment challenge. Expert Rev. Neurother. 2013 13 10 1099 1105 10.1586/14737175.2013.840419 24117272
    [Google Scholar]
  68. Rodriguez A. Brown C. Badie B. Chimeric antigen receptor T-cell therapy for glioblastoma. Transl. Res. 2017 187 93 102 10.1016/j.trsl.2017.07.003 28755873
    [Google Scholar]
  69. Brown C.E. Alizadeh D. Starr R. Weng L. Wagner J.R. Naranjo A. Ostberg J.R. Blanchard M.S. Kilpatrick J. Simpson J. Kurien A. Priceman S.J. Wang X. Harshbarger T.L. D’Apuzzo M. Ressler J.A. Jensen M.C. Barish M.E. Chen M. Portnow J. Forman S.J. Badie B. Regression of glioblastoma after chimeric antigen receptor T-Cell therapy. N. Engl. J. Med. 2016 375 26 2561 2569 10.1056/NEJMoa1610497 28029927
    [Google Scholar]
  70. Klampatsa A. Dimou V. Albelda S.M. Mesothelin-targeted CAR-T cell therapy for solid tumors. Expert Opin. Biol. Ther. 2021 21 4 473 486 10.1080/14712598.2021.1843628 33176519
    [Google Scholar]
  71. Morgan R.A. Yang J.C. Kitano M. Dudley M.E. Laurencot C.M. Rosenberg S.A. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18 4 843 851 2010 10.1038/mt.2010.24
    [Google Scholar]
  72. Ahmed N. Brawley V.S. Hegde M. Robertson C. Ghazi A. Gerken C. Liu E. Dakhova O. Ashoori A. Corder A. Gray T. Wu M.F. Liu H. Hicks J. Rainusso N. Dotti G. Mei Z. Grilley B. Gee A. Rooney C.M. Brenner M.K. Heslop H.E. Wels W.S. Wang L.L. Anderson P. Gottschalk S. Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T Cells for the immunotherapy of HER2-positive sarcoma. J. Clin. Oncol. 2015 33 15 1688 1696 10.1200/JCO.2014.58.0225 25800760
    [Google Scholar]
  73. Katz S.C. Moody A.E. Guha P. Hardaway J.C. Prince E. LaPorte J. Stancu M. Slansky J.E. Jordan K.R. Schulick R.D. Knight R. Saied A. Armenio V. Junghans R.P. HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery. J. Immunother. Cancer 2020 8 2 e001097 10.1136/jitc‑2020‑001097 32843493
    [Google Scholar]
  74. Kershaw M.H. Westwood J.A. Parker L.L. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer Clin. Cancer Res. 2006 12 20 Pt 1 6106 6115 10.1158/1078‑0432.CCR‑06‑1183
    [Google Scholar]
  75. Aithal A. Rauth S. Kshirsagar P. Shah A. Lakshmanan I. Junker W.M. Jain M. Ponnusamy M.P. Batra S.K. MUC16 as a novel target for cancer therapy. Expert Opin. Ther. Targets 2018 22 8 675 686 10.1080/14728222.2018.1498845 29999426
    [Google Scholar]
  76. Hassan R. Bera T. Pastan I. Mesothelin: A new target for immunotherapy Cli. Cancer Res. 10 12 Pt 1 3937 3942 2004 10.1158/1078‑0432.CCR‑03‑0801
    [Google Scholar]
  77. Morello A. Sadelain M. Adusumilli P.S. Mesothelin-targeted CARs: Driving T cells to solid tumors. Cancer Discov. 2016 6 2 133 146 10.1158/2159‑8290.CD‑15‑0583 26503962
    [Google Scholar]
  78. Mohabati Mobarez A. Soleimani N. Esmaeili S.A. Farhangi B. Nanoparticle-based immunotherapy of breast cancer using recombinant Helicobacter pylori proteins. Eur. J. Pharm. Biopharm. 2020 155 69 76 10.1016/j.ejpb.2020.08.013 32798667
    [Google Scholar]
  79. Maus M.V. Haas A.R. Beatty G.L. Albelda S.M. Levine B.L. Liu X. Zhao Y. Kalos M. June C.H. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol. Res. 2013 1 1 26 31 10.1158/2326‑6066.CIR‑13‑0006 24777247
    [Google Scholar]
  80. Haas A.R. Tanyi J.L. O'Hara M.H. Phase I study of lentiviral- transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers. Mol. Ther. 27 11 1919 1929 2019 10.1016/j.ymthe.2019.07.015
    [Google Scholar]
  81. Adusumilli P.S. Zauderer M.G. Rivière I. Solomon S.B. Rusch V.W. O’Cearbhaill R.E. Zhu A. Cheema W. Chintala N.K. Halton E. Pineda J. Perez-Johnston R. Tan K.S. Daly B. Araujo Filho J.A. Ngai D. McGee E. Vincent A. Diamonte C. Sauter J.L. Modi S. Sikder D. Senechal B. Wang X. Travis W.D. Gönen M. Rudin C.M. Brentjens R.J. Jones D.R. Sadelain M. 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. 2021 11 11 2748 2763 10.1158/2159‑8290.CD‑21‑0407 34266984
    [Google Scholar]
  82. Wang Z. Li N. Feng K. Chen M. Zhang Y. Liu Y. Yang Q. Nie J. Tang N. Zhang X. Cheng C. Shen L. He J. Ye X. Cao W. Wang H. Han W. Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors. Cell. Mol. Immunol. 2021 18 9 2188 2198 10.1038/s41423‑021‑00749‑x 34381179
    [Google Scholar]
  83. Hassan R. Butler M. O'Cearbhaill R.E. Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: Phase 1/2 trial interim results. Nat. Med. 29 8 2099 2109 2023 10.1038/s41591‑023‑02452‑y
    [Google Scholar]
  84. Maalej K.M. Merhi M. Inchakalody V.P. Mestiri S. Alam M. Maccalli C. Cherif H. Uddin S. Steinhoff M. Marincola F.M. Dermime S. CAR-cell therapy in the era of solid tumor treatment: Current challenges and emerging therapeutic advances. Mol. Cancer 2023 22 1 20 10.1186/s12943‑023‑01723‑z 36717905
    [Google Scholar]
  85. Shi D. Shi Y. Kaseb A.O. Qi X. Zhang Y. Chi J. Lu Q. Gao H. Jiang H. Wang H. Yuan D. Ma H. Wang H. Li Z. Zhai B. Chimeric antigen receptor-glypican-3 T-cell therapy for advanced hepatocellular carcinoma: Results of phase I trials. Clin. Cancer Res. 2020 26 15 3979 3989 10.1158/1078‑0432.CCR‑19‑3259 32371538
    [Google Scholar]
  86. Guo J. Tang Q. Recent updates on chimeric antigen receptor T cell therapy for hepatocellular carcinoma. Cancer Gene Ther. 2021 28 10-11 1075 1087 10.1038/s41417‑020‑00259‑4 33500535
    [Google Scholar]
  87. Wang Y. Chen M. Wu Z. Tong C. Dai H. Guo Y. Liu Y. Huang J. Lv H. Luo C. Feng K. Yang Q. Li X. Han W. CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial. OncoImmunology 2018 7 7 e1440169 10.1080/2162402X.2018.1440169 29900044
    [Google Scholar]
  88. Patel U. Abernathy J. Savani B N. Oluwole O. Sengsayadeth S. Dholaria B. CAR T cell therapy in solid tumors: A review of current clinical trials EJHaem 2022 3 Suppl 1 24 31 10.1002/jha2.356
    [Google Scholar]
  89. Parizi P.K. Yarahmadi F. Tabar H.M. Hosseini Z. Sarli A. Kia N. Tafazoli A. Esmaeili S.A. MicroRNAs and target molecules in bladder cancer. Med. Oncol. 2020 37 12 118 10.1007/s12032‑020‑01435‑0 33216248
    [Google Scholar]
  90. Qi C. Zhang P. Liu C. Zhang J. Zhou J. Yuan J. Liu D. Zhang M. Gong J. Wang X. Li J. Zhang X. Li N. Peng X. Liu Z. Yuan D. Baffa R. Wang Y. Shen L. Safety and efficacy of CT041 in patients with refractory metastatic pancreatic cancer: A pooled analysis of two early-phase trials. J. Clin. Oncol. 2024 42 21 2565 2577 10.1200/JCO.23.02314 38788174
    [Google Scholar]
  91. Louis C.U. Savoldo B. Dotti G. Pule M. Yvon E. Myers G.D. Rossig C. Russell H.V. Diouf O. Liu E. Liu H. Wu M.F. Gee A.P. Mei Z. Rooney C.M. Heslop H.E. Brenner M.K. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 2011 118 23 6050 6056 10.1182/blood‑2011‑05‑354449 21984804
    [Google Scholar]
  92. Haffner M.C. Kronberger I.E. Ross J.S. Sheehan C.E. Zitt M. Mühlmann G. Öfner D. Zelger B. Ensinger C. Yang X.J. Geley S. Margreiter R. Bander N.H. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum. Pathol. 2009 40 12 1754 1761 10.1016/j.humpath.2009.06.003 19716160
    [Google Scholar]
  93. Esmaeili S-A. Nejatollahi F. Sahebkar A. Inhibition of intercellular communication between prostate cancer cells by a specific Anti-STEAP-1 single chain antibody. Anticancer Agents Med. Chem. 2018 18 12 1674 1679 10.2174/1871520618666171208092115 29219059
    [Google Scholar]
  94. Bilusic M. Madan R.A. Gulley J.L. Immunotherapy of prostate cancer: Facts and hopes. Clin. Cancer Res. 2017 23 22 6764 6770 10.1158/1078‑0432.CCR‑17‑0019 28663235
    [Google Scholar]
  95. Junghans R.P. Ma Q. Rathore R. Gomes E.M. Bais A.J. Lo A.S.Y. Abedi M. Davies R.A. Cabral H.J. Al-Homsi A.S. Cohen S.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. Prostate 2016 76 14 1257 1270 10.1002/pros.23214 27324746
    [Google Scholar]
  96. Moon E.K. Wang L.C.S. Bekdache K. Lynn R.C. Lo A. Thorne S.H. Albelda S.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. OncoImmunology 2018 7 3 e1395997 10.1080/2162402X.2017.1395997 29399394
    [Google Scholar]
  97. Nishio N. Diaconu I. Liu H. Cerullo V. Caruana I. Hoyos V. Bouchier-Hayes L. Savoldo B. Dotti G. Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors. Cancer Res. 2014 74 18 5195 5205 10.1158/0008‑5472.CAN‑14‑0697 25060519
    [Google Scholar]
  98. Hong M. Puaux A.L. Huang C. Loumagne L. Tow C. Mackay C. Kato M. Prévost-Blondel A. Avril M.F. Nardin A. Abastado J.P. Chemotherapy induces intratumoral expression of chemokines in cutaneous melanoma, favoring T-cell infiltration and tumor control. Cancer Res. 2011 71 22 6997 7009 10.1158/0008‑5472.CAN‑11‑1466 21948969
    [Google Scholar]
  99. Kanagawa N. Niwa M. Hatanaka Y. Tani Y. Nakagawa S. Fujita T. Yamamoto A. Okada N. 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. Cancer 2007 121 9 2013 2022 10.1002/ijc.22908 17621629
    [Google Scholar]
  100. Tchou J. Zhao Y. Levine B.L. Zhang P.J. Davis M.M. Melenhorst J.J. Kulikovskaya I. Brennan A.L. Liu X. Lacey S.F. Posey A.D. Williams A.D. So A. Conejo-Garcia J.R. Plesa G. Young R.M. McGettigan S. Campbell J. Pierce R.H. Matro J.M. DeMichele A.M. Clark A.S. Cooper L.J. Schuchter L.M. Vonderheide R.H. June C.H. Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer. Cancer Immunol. Res. 2017 5 12 1152 1161 10.1158/2326‑6066.CIR‑17‑0189 29109077
    [Google Scholar]
  101. Jin L. Tao H. Karachi A. Long Y. Hou A.Y. Na M. Dyson K.A. Grippin A.J. Deleyrolle L.P. Zhang W. Rajon D.A. Wang Q.J. Yang J.C. Kresak J.L. Sayour E.J. Rahman M. Bova F.J. Lin Z. Mitchell D.A. Huang J. CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Nat. Commun. 2019 10 1 4016 10.1038/s41467‑019‑11869‑4 31488817
    [Google Scholar]
  102. Whilding L. Halim L. Draper B. Parente-Pereira A. Zabinski T. Davies D. Maher J. 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) 2019 11 5 674 10.3390/cancers11050674 31091832
    [Google Scholar]
  103. Caruana I. Savoldo B. Hoyos V. Weber G. Liu H. Kim E.S. Ittmann M.M. Marchetti D. Dotti G. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat. Med. 2015 21 5 524 529 10.1038/nm.3833 25849134
    [Google Scholar]
  104. Wang L.C.S. Lo A. Scholler J. Sun J. Majumdar R.S. Kapoor V. Antzis M. Cotner C.E. Johnson L.A. Durham A.C. Solomides C.C. June C.H. Puré E. Albelda S.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. 2014 2 2 154 166 10.1158/2326‑6066.CIR‑13‑0027 24778279
    [Google Scholar]
  105. Sackstein R. The first step in adoptive cell immunotherapeutics: Assuring cell delivery via glycoengineering. Front. Immunol. 2019 9 3084 10.3389/fimmu.2018.03084 30687313
    [Google Scholar]
  106. Deng C. Zhao J. Zhou S. Dong J. Cao J. Gao J. Bai Y. Deng H. The vascular disrupting agent CA4P improves the antitumor efficacy of CAR-T cells in preclinical models of solid human tumors. Mol. Ther. 2020 28 1 75 88 10.1016/j.ymthe.2019.10.010 31672285
    [Google Scholar]
  107. Wang W. Marín-Ramos N.I. He H. Zeng S. Cho H.Y. Swenson S.D. Zheng L. Epstein A.L. Schönthal A.H. Hofman F.M. Chen L. Chen T.C. NEO100 enables brain delivery of blood‒brain barrier impermeable therapeutics. Neuro-oncol. 2021 23 1 63 75 10.1093/neuonc/noaa206 32877532
    [Google Scholar]
  108. Chinnasamy D. Yu Z. Kerkar S.P. Zhang L. Morgan R.A. Restifo N.P. Rosenberg S.A. Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin. Cancer Res. 2012 18 6 1672 1683 10.1158/1078‑0432.CCR‑11‑3050 22291136
    [Google Scholar]
  109. Fu X. Rivera A. Tao L. Zhang X. Genetically modified T cells targeting neovasculature efficiently destroy tumor blood vessels, shrink established solid tumors and increase nanoparticle delivery. Int. J. Cancer 2013 133 10 2483 2492 10.1002/ijc.28269 23661285
    [Google Scholar]
  110. Juillerat A. Marechal A. Filhol J.M. Valogne Y. Valton J. Duclert A. Duchateau P. Poirot L. An oxygen sensitive self-decision making engineered CAR T-cell. Sci. Rep. 2017 7 1 39833 10.1038/srep39833 28106050
    [Google Scholar]
  111. Kosti P. Opzoomer J.W. Larios-Martinez K.I. Henley-Smith R. Scudamore C.L. Okesola M. Taher M.Y.M. Davies D.M. Muliaditan T. Larcombe-Young D. Woodman N. Gillett C.E. Thavaraj S. Maher J. Arnold J.N. Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors. Cell Rep. Med. 2021 2 4 100227 10.1016/j.xcrm.2021.100227 33948568
    [Google Scholar]
  112. Liao Q. He H. Mao Y. Ding X. Zhang X. Xu J. Engineering T cells with hypoxia-inducible chimeric antigen receptor (HiCAR) for selective tumor killing. Biomark. Res. 2020 8 1 56 10.1186/s40364‑020‑00238‑9 33292642
    [Google Scholar]
  113. Newick K. O’Brien S. Sun J. Kapoor V. Maceyko S. Lo A. Puré E. Moon E. Albelda S.M. Augmentation of CAR T-cell trafficking and antitumor efficacy by blocking protein kinase A localization. Cancer Immunol. Res. 2016 4 6 541 551 10.1158/2326‑6066.CIR‑15‑0263 27045023
    [Google Scholar]
  114. Tang J. Zou Y. Li L. Lu F. Xu H. Ren P. Bai F. Niedermann G. Zhu X. BAY 60-6583 enhances the antitumor function of chimeric antigen receptor-modified T cells independent of the adenosine A2b receptor. Front. Pharmacol. 2021 12 619800 10.3389/fphar.2021.619800 33776765
    [Google Scholar]
  115. Ligtenberg M.A. Mougiakakos D. Mukhopadhyay M. Witt K. Lladser A. Chmielewski M. Riet T. Abken H. Kiessling R. Coexpressed catalase protects chimeric antigen receptor-redirected T cells as well as bystander cells from oxidative stress-induced loss of antitumor activity. J. Immunol. 2016 196 2 759 766 10.4049/jimmunol.1401710 26673145
    [Google Scholar]
  116. Mane M.M. Cohen I.J. Ackerstaff E. Shalaby K. Ijoma J.N. Ko M. Maeda M. Albeg A.S. Vemuri K. Satagopan J. Moroz A. Zurita J. Shenker L. Shindo M. Nickles T. Nikolov E. Moroz M.A. Koutcher J.A. Serganova I. Ponomarev V. Blasberg R.G. Lactate dehydrogenase a depletion alters MyC-CaP tumor metabolism, microenvironment, and CAR T cell therapy. Mol. Ther. Oncolytics 2020 18 382 395 10.1016/j.omto.2020.07.006 32913888
    [Google Scholar]
  117. Suarez E.R. Chang D.K. Sun J. Sui J. Freeman G.J. Signoretti S. Zhu Q. Marasco W.A. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model. Oncotarget 2016 7 23 34341 34355 10.18632/oncotarget.9114 27145284
    [Google Scholar]
  118. Jung I.Y. Kim Y.Y. Yu H.S. Lee M. Kim S. Lee J. CRISPR/Cas9- mediated knockout of DGK improves antitumor activities of human T cells. Cancer Res. 2018 78 16 4692 4703 10.1158/0008‑5472.CAN‑18‑0030 29967261
    [Google Scholar]
  119. Marchesi F. Vignali D. Manini B. Rigamonti A. Monti P. Manipulation of glucose availability to boost cancer immunotherapies. Cancers (Basel) 2020 12 10 2940 10.3390/cancers12102940 33053779
    [Google Scholar]
  120. Long A.H. Haso W.M. Shern J.F. Wanhainen K.M. Murgai M. Ingaramo M. Smith J.P. Walker A.J. Kohler M.E. Venkateshwara V.R. Kaplan R.N. Patterson G.H. Fry T.J. Orentas R.J. Mackall C.L. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat. Med. 2015 21 6 581 590 10.1038/nm.3838 25939063
    [Google Scholar]
  121. Watanabe N. Bajgain P. Sukumaran S. Ansari S. Heslop H.E. Rooney C.M. Brenner M.K. Leen A.M. Vera J.F. Fine-tuning the CAR spacer improves T-cell potency. OncoImmunology 2016 5 12 e1253656 10.1080/2162402X.2016.1253656 28180032
    [Google Scholar]
  122. Cherkassky L. Morello A. Villena-Vargas J. Feng Y. Dimitrov D.S. Jones D.R. Sadelain M. Adusumilli P.S. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J. Clin. Invest. 2016 126 8 3130 3144 10.1172/JCI83092 27454297
    [Google Scholar]
  123. Liu X. Ranganathan R. Jiang S. Fang C. Sun J. Kim S. Newick K. Lo A. June C.H. Zhao Y. Moon E.K. A chimeric switch-receptor targeting PD1 augments the efficacy of second-generation CAR T cells in advanced solid tumors. Cancer Res. 2016 76 6 1578 1590 10.1158/0008‑5472.CAN‑15‑2524 26979791
    [Google Scholar]
  124. Bailey S.R. Maus M.V. Gene editing for immune cell therapies. Nat. Biotechnol. 2019 37 12 1425 1434 10.1038/s41587‑019‑0137‑8 31160723
    [Google Scholar]
  125. Choi B.D. Yu X. Castano A.P. Bouffard A.A. Schmidts A. Larson R.C. Bailey S.R. Boroughs A.C. Frigault M.J. Leick M.B. Scarfò I. Cetrulo C.L. Demehri S. Nahed B.V. Cahill D.P. Wakimoto H. Curry W.T. Carter B.S. Maus M.V. CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. Nat. Biotechnol. 2019 37 9 1049 1058 10.1038/s41587‑019‑0192‑1 31332324
    [Google Scholar]
  126. Lohmueller J.J. Ham J.D. Kvorjak M. Finn O.J. mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting. OncoImmunology 2018 7 1 e1368604 10.1080/2162402X.2017.1368604 29296519
    [Google Scholar]
  127. Urbanska K. Lanitis E. Poussin M. Lynn R.C. Gavin B.P. Kelderman S. Yu J. Scholler N. Powell D.J. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res. 2012 72 7 1844 1852 10.1158/0008‑5472.CAN‑11‑3890 22315351
    [Google Scholar]
  128. Cho J.H. Collins J.J. Wong W.W. Universal chimeric antigen receptors for multiplexed and logical control of T cell responses. Cell 2018 173 6 1426 1438.e11 10.1016/j.cell.2018.03.038 29706540
    [Google Scholar]
  129. Wilkie S. Burbridge S.E. Chiapero-Stanke L. Pereira A.C.P. Cleary S. van der Stegen S.J.C. Spicer J.F. Davies D.M. Maher J. Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. J. Biol. Chem. 2010 285 33 25538 25544 10.1074/jbc.M110.127951 20562098
    [Google Scholar]
  130. Koneru M. Purdon T.J. Spriggs D. Koneru S. Brentjens R.J. IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo. OncoImmunology 2015 4 3 e994446 10.4161/2162402X.2014.994446 25949921
    [Google Scholar]
  131. Mohammed S. Sukumaran S. Bajgain P. Improving chimeric antigen receptor-modified T cell function by reversing the immunosuppressive tumor microenvironment of pancreatic cancer. Mol. Ther. 2017 25 1 249 258 10.1016/j.ymthe.2016.10.016
    [Google Scholar]
  132. Becerra C.R. Manji G.A. Kim D.W. Gardner O. Malankar A. Shaw J. Blass D. Yi X. Foster A.E. Woodard P. 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. 2019 37 Suppl 15 2536 2536 10.1200/JCO.2019.37.15_suppl.2536
    [Google Scholar]
  133. Hegde M. DeRenzo C.C. Zhang H. Mata M. Gerken C. Shree A. Yi Z. Brawley V. Dakhova O. Wu M-F. Liu H. Hicks J. Grilley B. Gee A.P. Rooney C.M. Brenner M.K. Heslop H.E. Wels W. Gottschalk S. Ahmed N.M. Expansion of HER2- CAR T cells after lymphodepletion and clinical responses in patients with advanced sarcoma. J. Clin. Oncol. 2017 35 Suppl 15 10508 10508 10.1200/JCO.2017.35.15_suppl.10508
    [Google Scholar]
  134. Shahverdi M. Hajiasgharzadeh K. Sorkhabi A.D. The regulatory role of autophagy-related miRNAs in lung cancer drug resistance Biomed. Pharmacother. 2022 148 112735 10.1016/j.biopha.2022.112735
    [Google Scholar]
  135. Wang Z. Wu Z. Liu Y. Han W. New development in CAR-T cell therapy. J. Hematol. Oncol. 2017 10 1 53 10.1186/s13045‑017‑0423‑1 28222796
    [Google Scholar]
  136. Hegde M. Mukherjee M. Grada Z. Pignata A. Landi D. Navai S.A. Wakefield A. Fousek K. Bielamowicz K. Chow K.K.H. Brawley V.S. Byrd T.T. Krebs S. Gottschalk S. Wels W.S. Baker M.L. Dotti G. Mamonkin M. Brenner M.K. Orange J.S. Ahmed N. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape. J. Clin. Invest. 2016 126 8 3036 3052 10.1172/JCI83416 27427982
    [Google Scholar]
  137. Fedorov V.D. Themeli M. Sadelain M. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci. Transl. Med. 2013 5 215 215ra172 10.1126/scitranslmed.3006597 24337479
    [Google Scholar]
  138. Diaconu I. Ballard B. Zhang M. Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells Mol. Ther. 2017 25 3 580 592 10.1016/j.ymthe.2017.01.011
    [Google Scholar]
  139. Gargett T. Brown M.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. 2014 5 235 10.3389/fphar.2014.00235 25389405
    [Google Scholar]
  140. Sentman C.L. Meehan K.R. NKG2D CARs as cell therapy for cancer. Cancer J. 2014 20 2 156 159 10.1097/PPO.0000000000000029 24667963
    [Google Scholar]
  141. Zhang T. Barber A. Sentman C.L. Chimeric NKG2D modified T cells inhibit systemic T-cell lymphoma growth in a manner involving multiple cytokines and cytotoxic pathways. Cancer Res. 2007 67 22 11029 11036 10.1158/0008‑5472.CAN‑07‑2251 18006849
    [Google Scholar]
  142. Chmielewski M. Abken H. TRUCKs: The fourth generation of CARs. Expert Opin. Biol. Ther. 2015 15 8 1145 1154 10.1517/14712598.2015.1046430 25985798
    [Google Scholar]
  143. Chinnasamy D. Yu Z. Theoret M.R. Zhao Y. Shrimali R.K. Morgan R.A. Feldman S.A. Restifo N.P. Rosenberg S.A. Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice. J. Clin. Invest. 2010 120 11 3953 3968 10.1172/JCI43490 20978347
    [Google Scholar]
  144. June C.H. O’Connor R.S. Kawalekar O.U. Ghassemi S. Milone M.C. CAR T cell immunotherapy for human cancer. Science 2018 359 6382 1361 1365 10.1126/science.aar6711 29567707
    [Google Scholar]
  145. Potez M. Snedal S. She C. Use of phage display biopanning as a tool to design CAR-T cells against glioma stem cells Front. Oncol. 13 1124272 2023 10.3389/fonc.2023.1124272
    [Google Scholar]
  146. Yang F. Zhang F. Ji F. Chen J. Li J. Chen Z. Hu Z. Guo Z. Self-delivery of TIGIT-blocking scFv enhances CAR-T immunotherapy in solid tumors. Front. Immunol. 2023 14 1175920 10.3389/fimmu.2023.1175920 37359558
    [Google Scholar]
  147. Swan S.L. Mehta N. Ilich E. Shen S.H. Wilkinson D.S. Anderson A.R. Segura T. Sanchez-Perez L. Sampson J.H. Bellamkonda R.V. IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma. Front. Immunol. 2023 14 1085547 10.3389/fimmu.2023.1085547 36817432
    [Google Scholar]
  148. Suntharalingam G. Perry M.R. Ward S. Brett S.J. Castello-Cortes A. Brunner M.D. Panoskaltsis N. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N. Engl. J. Med. 2006 355 10 1018 1028 10.1056/NEJMoa063842 16908486
    [Google Scholar]
  149. Teachey D.T. Lacey S.F. Shaw P.A. Melenhorst J.J. Maude S.L. Frey N. Pequignot E. Gonzalez V.E. Chen F. Finklestein J. Barrett D.M. Weiss S.L. Fitzgerald J.C. Berg R.A. Aplenc R. Callahan C. Rheingold S.R. Zheng Z. Rose-John S. White J.C. Nazimuddin F. Wertheim G. Levine B.L. June C.H. Porter D.L. Grupp S.A. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discov. 2016 6 6 664 679 10.1158/2159‑8290.CD‑16‑0040 27076371
    [Google Scholar]
  150. Lee D.W. Gardner R. Porter D.L. Louis C.U. Ahmed N. Jensen M. Grupp S.A. Mackall C.L. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014 124 2 188 195 10.1182/blood‑2014‑05‑552729 24876563
    [Google Scholar]
  151. Milone M.C. Bhoj V.G. The pharmacology of T cell therapies. Mol. Ther. Methods Clin. Dev. 2018 8 210 221 10.1016/j.omtm.2018.01.010 29552577
    [Google Scholar]
  152. Messmer A.S. Que Y.A. Schankin C. Banz Y. Bacher U. Novak U. Pabst T. CAR T-cell therapy and critical care. Wien. Klin. Wochenschr. 2021 133 23-24 1318 1325 10.1007/s00508‑021‑01948‑2 34613477
    [Google Scholar]
  153. Murthy H.S. Yassine F. Iqbal M. Alotaibi S. Moustafa M.A. Kharfan-Dabaja M.A. Management of CAR T-cell related toxicities: What did the learning curve teach us so far? Hematol. Oncol. Stem Cell Ther. 2022 15 3 100 111 10.56875/2589‑0646.1029 36395496
    [Google Scholar]
  154. Jain T. Olson T.S. Locke F.L. How I treat cytopenias after CAR T- cell therapy. Blood 2023 141 20 blood.2022017415 10.1182/blood.2022017415 36800563
    [Google Scholar]
  155. Stewart A.G. Henden A.S. Infectious complications of CAR T-cell therapy: A clinical update. Ther. Adv. Infect. Dis. 2021 8 20499361211036773 10.1177/20499361211036773 34457269
    [Google Scholar]
  156. Mohammadi S. Abdollahi E. Nezamnia M. Adoptive transfer of Tregs: A novel strategy for cell-based immunotherapy in spontaneous abortion: Lessons from experimental models Int. Immunopharmacol. 90 2021 107195 10.1016/j.intimp.2020.107195
    [Google Scholar]
  157. Dasyam N. George P. Weinkove R. Chimeric antigen receptor T- cell therapies: Optimising the dose. Br. J. Clin. Pharmacol. 2020 86 9 1678 1689 10.1111/bcp.14281 32175617
    [Google Scholar]
  158. Mitchell E. Vassiliou G.S. T-cell cancer after CAR T-cell therapy. N. Engl. J. Med. 2024 390 22 2120 2121 10.1056/NEJMe2405538 38865665
    [Google Scholar]
  159. Hamilton M.P. Sugio T. Noordenbos T. Shi S. Bulterys P.L. Liu C.L. Kang X. Olsen M.N. Good Z. Dahiya S. Frank M.J. Sahaf B. Mackall C.L. Gratzinger D. Diehn M. Alizadeh A.A. Miklos D.B. Risk of second tumors and T-cell lymphoma after CAR T-cell therapy. N. Engl. J. Med. 2024 390 22 2047 2060 10.1056/NEJMoa2401361 38865660
    [Google Scholar]
  160. Ozdemirli M. Loughney T.M. Deniz E. Chahine J.J. Albitar M. Pittaluga S. Sadigh S. Armand P. Uren A. Anderson K.C. Indolent CD4+ CAR T-cell lymphoma after cilta-cel CAR T-cell therapy. N. Engl. J. Med. 2024 390 22 2074 2082 10.1056/NEJMoa2401530 38865661
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128336391241107112957
Loading
Revolutionizing Cancer Treatment: Unveiling the Power of CAR T-cell Therapy
Bentham Science Publishers ; https://doi.org/10.2174/0113816128336391241107112957
/content/journals/cpd/10.2174/0113816128336391241107112957
/content/journals/cpd/10.2174/0113816128336391241107112957
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: treatment ; oncology ; malignancy ; CAR T-cell ; tumour ; Cancer ; side effects ; immunotherapy

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test