Login Register Cart 0
Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Chimeric Antigen Receptor-Engineered T-Cells - A New Way and Era for Lymphoma Treatment

Author(s): Romeo G. Mihăilă*

Volume 14, Issue 4, 2019

Page: [312 - 323] Pages: 12

DOI: 10.2174/1574892814666191022164641

Price: $65

Abstract

Background: Patients with refractory or relapsed diffuse large B-cell lymphoma have a poor prognosis with the current standard of care.

Objective: Chimeric Antigen Receptor T-cells (CAR T-cells) are functionally reprogrammed lymphocytes, which are able to recognize and kill tumor cells. The aim of this study is to make progress in this area.

Methods: A mini-review was achieved using the articles published in Web of Science and PubMed in the last year and the new patents were made in this field.

Results: The responses to CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel are promising; the objective response rate can reach up to 83%, and the complete response rate ranges between 40 and 58%. About half of the patients may have serious side effects, such as cytokine release syndrome and neurotoxicity. Current and future developments include the improvement of CAR T-cell expansion and polyfunctionality, the combined use of CAR T-cells with a fusion protein between interferon and an anti-CD20 monoclonal antibody, with checkpoint inhibitors or small molecule sensitizers that have apoptotic-regulatory effects. Furthermore, the use of IL-12-expressing CAR T-cells, an improved technology for the production of CAR T-cells based on targeted nucleases, the widespread use of allogeneic CAR T-cells or universal CAR T-cells obtained from genetically engineered healthy donor T-cells are future developments actively considered.

Conclusion: CAR T-cell therapy significantly improved the outcome of patients with relapsed or refractory diffuse large B-cell lymphoma. The advances in CAR T-cells production technology will improve the results and enable the expansion of this new immunotherapy.

Keywords: Axicabtagene ciloleucel, chimeric antigen receptor, cytokine release syndrome, diffuse large B-cell lymphoma, tisagenlecleucel, tocilizumab.

« Previous Next »
[1]
Lulla PD, Hill LC, Ramos CA, Heslop HE. The use of chimeric antigen receptor T cells in patients with non-Hodgkin lymphoma. Clin Adv Hematol Oncol 2018; 16(5): 375-86.
[PMID: 29851933]
[2]
Gisselbrecht C, Van Den Neste E. How I manage patients with relapsed/refractory diffuse large B cell lymphoma. Br J Haematol 2018; 182(5): 633-43.
[http://dx.doi.org/10.1111/bjh.15412] [PMID: 29808921]
[3]
Chavez JC, Locke FL. CAR T cell therapy for B-cell lymphomas. Best Pract Res Clin Haematol 2018; 31(2): 135-46.
[http://dx.doi.org/10.1016/j.beha.2018.04.001] [PMID: 29909914]
[4]
Jain MD, Davila ML. Concise review: Emerging principles from the clinical application of chimeric antigen receptor T cell therapies for B cell malignancies. Stem Cells 2018; 36(1): 36-44.
[http://dx.doi.org/10.1002/stem.2715] [PMID: 29024301]
[5]
Perales MA, Kebriaei P, Kean LS, Sadelain M. Building a safer and faster CAR: Seatbelts, airbags, and CRISPR. Biol Blood Marrow Transplant 2018; 24(1): 27-31.
[http://dx.doi.org/10.1016/j.bbmt.2017.10.017] [PMID: 29032264]
[6]
Zou Y, Xu W, Li J. Chimeric antigen receptor-modified T cell therapy in chronic lymphocytic leukemia. J Hematol Oncol 2018; 11(1): 130.
[http://dx.doi.org/10.1186/s13045-018-0676-3] [PMID: 30458878]
[7]
Pehlivan KC, Duncan BB, Lee DW. CAR-T cell therapy for acute lymphoblastic leukemia: Transforming the treatment of relapsed and refractory disease. Curr Hematol Malig Rep 2018; 13(5): 396-406.
[http://dx.doi.org/10.1007/s11899-018-0470-x] [PMID: 30120708]
[8]
Nair R, Neelapu SS. The promise of CAR T-cell therapy in aggressive B-cell lymphoma. Best Pract Res Clin Haematol 2018; 31(3): 293-8.
[http://dx.doi.org/10.1016/j.beha.2018.07.011] [PMID: 30213399]
[9]
Chow VA, Shadman M, Gopal AK. Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma. Blood 2018; 132(8): 777-81.
[http://dx.doi.org/10.1182/blood-2018-04-839217] [PMID: 29914976]
[10]
Perica K, Curran KJ, Brentjens RJ, Giralt SA. Building a CAR garage: Preparing for the delivery of commercial CAR T cell products at Memorial Sloan Kettering Cancer Center. Biol Blood Marrow Transplant 2018; 24(6): 1135-41.
[http://dx.doi.org/10.1016/j.bbmt.2018.02.018] [PMID: 29499327]
[11]
Brudno JN, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for lymphoma. Nat Rev Clin Oncol 2018; 15(1): 31-46.
[http://dx.doi.org/10.1038/nrclinonc.2017.128] [PMID: 28857075]
[12]
Bouchkouj N, Kasamon YL, de Claro RA, George B, Lin X, Lee S, et al. FDA approval summary: Axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma. Clin Cancer Res 2019; 25(6): 1702-8.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-2743] [PMID: 30413526]
[13]
Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A. Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma 2018; 59(8): 1785-96.
[http://dx.doi.org/10.1080/10428194.2017.1387905] [PMID: 29058502]
[14]
Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): A single-arm, multicentre, Phase 1-2 trial. Lancet Oncol 2019; 20(1): 31-42.
[http://dx.doi.org/10.1016/S1470-2045(18)30864-7] [PMID: 30518502]
[15]
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 2019; 380(1): 45-56.
[http://dx.doi.org/10.1056/NEJMoa1804980] [PMID: 30501490]
[16]
Bao F, Hu K, Wan W, Tian L, Jing HM. Efficacy of anti-CD19 CAR-T cell therapy in 10 refractory recurrent B cell malignancies. Zhonghua Xue Ye Xue Za Zhi 2018; 39(6): 454-9.
[PMID: 30032559]
[17]
Enblad G, Karlsson H, Gammelgård G, Wenthe J, Lövgren T, Amini RM, et al. A Phase I/IIa trial using CD19-targeted third-generation CAR T cells for lymphoma and leukemia. Clin Cancer Res 2018; 24(24): 6185-94.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0426] [PMID: 30097433]
[18]
Zhu F, Shah N, Xu H, Schneider D, Orentas R, Dropulic B, et al. Closed-system manufacturing of CD19 and dual-targeted CD20/19 chimeric antigen receptor T cells using the CliniMACS Prodigy device at an academic medical center. Cytotherapy 2018; 20(3): 394-406.
[http://dx.doi.org/10.1016/j.jcyt.2017.09.005] [PMID: 29287970]
[19]
Zhang W, Jordan KR, Schulte B, Purev E. Characterization of clinical grade CD19 chimeric antigen receptor T cells produced using automated CliniMACS Prodigy system. Drug Des Devel Ther 2018; 12: 3343-56.
[http://dx.doi.org/10.2147/DDDT.S175113] [PMID: 30323566]
[20]
Strati P, Patel S, Nastoupil L, Fanale MA, Bollard CM, Lin AY, et al. Beyond chemotherapy: Checkpoint inhibition and cell-based therapy in Non-Hodgkin lymphoma. Am Soc Clin Oncol Educ Book 2018; 38(38): 592-603.
[http://dx.doi.org/10.1200/EDBK_200549] [PMID: 30231316]
[21]
Castella M, Boronat A, Martín-Ibáñez R, Rodríguez V, Suñé G, Caballero M, et al. Development of a novel anti-CD19 chimeric antigen receptor: A paradigm for an affordable CAR T cell production at Academic Institutions. Mol Ther Methods Clin Dev 2018; 12: 134-44.
[http://dx.doi.org/10.1016/j.omtm.2018.11.010] [PMID: 30623002]
[22]
Kasakovski D, Xu L, Li Y. T cell senescence and CAR-T cell exhaustion in hematological malignancies. J Hematol Oncol 2018; 11(1): 91.
[http://dx.doi.org/10.1186/s13045-018-0629-x] [PMID: 29973238]
[23]
Nahas MR, Rosenblatt J, Lazarus HM, Avigan D. Anti-cancer vaccine therapy for hematologic malignancies: An evolving era. Blood Rev 2018; 32(4): 312-25.
[http://dx.doi.org/10.1016/j.blre.2018.02.002] [PMID: 29475779]
[24]
Alcantara M, Tesio M, June CH, Houot R. CAR T-cells for T-cell malignancies: Challenges in distinguishing between therapeutic, normal, and neoplastic T-cells. Leukemia 2018; 32(11): 2307-15.
[http://dx.doi.org/10.1038/s41375-018-0285-8] [PMID: 30315238]
[25]
Hay KA. Cytokine release syndrome and neurotoxicity after CD19 chimeric antigen receptor-modified (CAR-) T cell therapy. Br J Haematol 2018; 183(3): 364-74.
[http://dx.doi.org/10.1111/bjh.15644] [PMID: 30407609]
[26]
Brudno JN, Kochenderfer JN. Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management. Blood Rev 2019; 34: 45-55.
[PMID: 30528964]
[27]
Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol 2018; 15(1): 47-62.
[http://dx.doi.org/10.1038/nrclinonc.2017.148] [PMID: 28925994]
[28]
Jin Z, Xiang R, Qing K, Li X, Zhang Y, Wang L, et al. The severe cytokine release syndrome in Phase I trials of CD19-CAR-T cell therapy: A systematic review. Ann Hematol 2018; 97(8): 1327-35.
[http://dx.doi.org/10.1007/s00277-018-3368-8] [PMID: 29766234]
[29]
Ding L, Hu Y, Zhao K, Wei G, Wu W, Wu Z, et al. Pleural cavity cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy: A case report. Medicine (Baltimore) 2018; 97(7)e9992
[http://dx.doi.org/10.1097/MD.0000000000009992] [PMID: 29443792]
[30]
Porter D, Frey N, Wood PA, Weng Y, Grupp SA. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J Hematol Oncol 2018; 11(1): 35.
[http://dx.doi.org/10.1186/s13045-018-0571-y] [PMID: 29499750]
[31]
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019; 25(4): 625-38.
[http://dx.doi.org/10.1016/j.bbmt.2018.12.758] [PMID: 30592986]
[32]
Ueda M, Berger M, Gale RP, Lazarus HM. Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation. Blood Rev 2018; 32(2): 106-15.
[http://dx.doi.org/10.1016/j.blre.2017.09.003] [PMID: 28958644]
[33]
Zhang WY, Liu Y, Wang Y, Nie J, Guo YL, Wang CM, et al. Excessive activated T-cell proliferation after anti-CD19 CAR T-cell therapy. Gene Ther 2018; 25(3): 198-204.
[http://dx.doi.org/10.1038/s41434-017-0001-8] [PMID: 29599530]
[34]
Hill JA, Li D, Hay KA, Green ML, Cherian S, Chen X, et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood 2018; 131(1): 121-30.
[http://dx.doi.org/10.1182/blood-2017-07-793760] [PMID: 29038338]
[35]
Chakraborty R, Sidana S, Shah GL, Scordo M, Hamilton BK, Majhail NS. Patient-reported outcomes with chimeric antigen receptor T cell therapy: Challenges and opportunities. Biol Blood Marrow Transplant 2019; 25(5): e155-62.
[http://dx.doi.org/10.1016/j.bbmt.2018.11.025] [PMID: 30500439]
[36]
Liu Y, Chen X, Wang D, Li H, Huang J, Zhang Z, et al. Hemofiltration successfully eliminates severe cytokine release syndrome following CD19 CAR-T-cell therapy. J Immunother 2018; 41(9): 406-10.
[http://dx.doi.org/10.1097/CJI.0000000000000243] [PMID: 30198955]
[37]
Pennell CA, Barnum JL, McDonald-Hyman CS, Panoskaltsis-Mortari A, Riddle MJ, Xiong Z, et al. Human CD19-targeted mouse T cells induce B Cell aplasia and toxicity in human CD19 transgenic mice. Mol Ther 2018; 26(6): 1423-34.
[http://dx.doi.org/10.1016/j.ymthe.2018.04.006] [PMID: 29735365]
[38]
Cooper ML, Choi J, Staser K, Ritchey JK, Devenport JM, Eckardt K, et al. An “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. Leukemia 2018; 32(9): 1970-83.
[http://dx.doi.org/10.1038/s41375-018-0065-5] [PMID: 29483708]
[39]
Avanzi MP, Yeku O, Li X, Wijewarnasuriya DP, van Leeuwen DG, Cheung K, et al. Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system. Cell Rep 2018; 23(7): 2130-41.
[http://dx.doi.org/10.1016/j.celrep.2018.04.051] [PMID: 29768210]
[40]
Petersen CT, Hassan M, Morris AB, Jeffery J, Lee K, Jagirdar N. et al. Improving T-cell expansion and function for adoptive T-cell therapy using ex vivo treatment with PI3Kδ inhibitors and VIP antagonists. Blood Adv 2018; 2(3): 210-23.
[http://dx.doi.org/10.1182/bloodadvances.2017011254] [PMID: 29386194]
[41]
Rossi J, Paczkowski P, Shen YW, Morse K, Flynn B, Kaiser A, et al. Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL. Blood 2018; 132(8): 804-14.
[http://dx.doi.org/10.1182/blood-2018-01-828343] [PMID: 29895668]
[42]
Pfeiffer A, Thalheimer FB, Hartmann S, Frank AM, Bender RR, Danisch S, et al. In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome. EMBO Mol Med 2018; 10(11)e9158
[http://dx.doi.org/10.15252/emmm.201809158] [PMID: 30224381]
[43]
Young PA, Yamada RE, Trinh KR, Vasuthasawat A, De Oliveira S, Yamada DH, et al. Activity of anti-CD19 chimeric antigen receptor T cells against B cell lymphoma is enhanced by antibody-targeted interferon-alpha. J Interferon Cytokine Res 2018; 38(6): 239-54.
[http://dx.doi.org/10.1089/jir.2018.0030] [PMID: 29920129]
[44]
Charalambous A, Schwarzbich MA, Witzens-Harig M. Ibrutinib. Recent Results Cancer Res 2018; 212: 133-68.
[http://dx.doi.org/10.1007/978-3-319-91439-8_7] [PMID: 30069629]
[45]
Zhu HB, Deng Q, Zhang R, Jiang YY, Meng JX, Zhao MF, et al. Effect of PD-1 inhibitor Nivolumab on the proliferation and cytotoxicity of anti-CD19 chimeric antigen receptor T cells. Zhonghua Xue Ye Xue Za Zhi 2018; 39(7): 584-8.
[PMID: 30122019]
[46]
Torres-Collado AX, Jazirehi AR. Overcoming resistance of human Non-Hodgkin’s lymphoma to CD19-CAR CTL therapy by celecoxib and histone deacetylase inhibitors. Cancers (Basel) 2018; 10(6) E200
[http://dx.doi.org/10.3390/cancers10060200] [PMID: 29904021]
[47]
Scarfò I, Ormhøj M, Frigault MJ, Castano AP, Lorrey S, Bouffard AA, et al. Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas. Blood 2018; 132(14): 1495-506.
[http://dx.doi.org/10.1182/blood-2018-04-842708] [PMID: 30089630]
[48]
Ebert LM, Yu W, Gargett T, Brown MP. Logic-gated approaches to extend the utility of chimeric antigen receptor T-cell technology. Biochem Soc Trans 2018; 46(2): 391-401.
[http://dx.doi.org/10.1042/BST20170178] [PMID: 29540509]
[49]
Rydzek J, Nerreter T, Peng H, Jutz S, Leitner J, Steinberger P, et al. Chimeric antigen receptor library screening using a novel NF-κB/NFAT reporter cell platform. Mol Ther 2019; 27(2): 287-99.
[http://dx.doi.org/10.1016/j.ymthe.2018.11.015] [PMID: 30573301]
[50]
Poggio T, Duyster J, Illert AL. Current immunotherapeutic approaches in T cell Non-Hodgkin lymphomas. Cancers (Basel) 2018; 10(9)E339
[http://dx.doi.org/10.3390/cancers10090339] [PMID: 30231561]
[51]
Zhao Z, Chen Y, Francisco NM, Zhang Y, Wu M. The application of CAR-T cell therapy in hematological malignancies: Advantages and challenges. Acta Pharm Sin B 2018; 8(4): 539-51.
[http://dx.doi.org/10.1016/j.apsb.2018.03.001] [PMID: 30109179]
[52]
Chen GH, Huang HW, Wang Y, Liu HW, Xu LJ, Ma X, et al. An experimental study of CD4 targeted chimeric antigen receptor modified T cell with anti-lymphoma activity. Zhonghua Xue Ye Xue Za Zhi 2018; 39(2): 148-52.
[PMID: 29562451]
[53]
De Munter S, Ingels J, Goetgeluk G, Bonte S, Pille M, Weening K, et al. Nanobody based dual specific CARs. Int J Mol Sci 2018; 19(2) E403
[http://dx.doi.org/10.3390/ijms19020403] [PMID: 29385713]
[54]
Mirzaei HR, Pourghadamyari H, Rahmati M, Mohammadi A, Nahand JS, Rezaei A, et al. Gene-knocked out chimeric antigen receptor (CAR) T cells: Tuning up for the next generation cancer immunotherapy. Cancer Lett 2018; 423: 95-104.
[http://dx.doi.org/10.1016/j.canlet.2018.03.010] [PMID: 29544719]
[55]
Kueberuwa G, Kalaitsidou M, Cheadle E, Hawkins RE, Gilham DE. CD19 CAR T cells expressing IL-12 eradicate lymphoma in fully lymphoreplete mice through induction of host immunity. Mol Ther Oncolytics 2017; 8: 41-51.
[http://dx.doi.org/10.1016/j.omto.2017.12.003] [PMID: 29367945]
[56]
Smith M, Zakrzewski J, James S, Sadelain M. Posttransplant chimeric antigen receptor therapy. Blood 2018; 131(10): 1045-52.
[http://dx.doi.org/10.1182/blood-2017-08-752121] [PMID: 29358181]
[57]
Liu E, Tong Y, Dotti G, Shaim H, Savoldo B, Mukherjee M, et al. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia 2018; 32(2): 520-31.
[http://dx.doi.org/10.1038/leu.2017.226] [PMID: 28725044]
[58]
McCreedy BJ, Senyukov VV, Nguyen KT. Off the shelf T cell therapies for hematologic malignancies. Best Pract Res Clin Haematol 2018; 31(2): 166-75.
[http://dx.doi.org/10.1016/j.beha.2018.03.001] [PMID: 29909917]
[59]
Nagle K, Tafuto B, Palladino Kim L, Parrott JS. Effect of transplant status in CD19-targeted CAR T-cell therapy: A systematic review and meta-analysis. Med Oncol 2018; 35(11): 144.
[http://dx.doi.org/10.1007/s12032-018-1204-6] [PMID: 30206753]
[60]
Appelbaum JS, Milano F. Hematopoietic stem cell transplantation in the era of engineered cell therapy. Curr Hematol Malig Rep 2018; 13(6): 484-93.
[http://dx.doi.org/10.1007/s11899-018-0476-4] [PMID: 30280289]
[61]
Till BG, Jensen MC, Wang J, Chen EY, Wood BL, Greisman HA, et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 2008; 112(6): 2261-71.
[http://dx.doi.org/10.1182/blood-2007-12-128843] [PMID: 18509084]
[62]
June CH, Levine BL, Porter DL, Kalos MD, Milone MC. Use of chimeric antigen receptor-modified T-cells to treat cancer US20130287748. (2013).
[63]
Pfeifer M, Zheng B, Erdmann T, Koeppen H, McCord R, Grau M, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015; 29(7): 1578-86.
[http://dx.doi.org/10.1038/leu.2015.48] [PMID: 25708834]
[64]
Brogdon J, June CH, Loew A, Maus M, Scholler J. Treatment of cancer using humanized anti-CD19 chimeric antigen receptor US20140271635. (2014).
[65]
Orentas RJ, Pastan IH, Dimitrov DS, Mackall CL. M971 chimeric antigen receptors US20150299317. (2015).
[66]
Young T, Kim C, Schultz PG. Peptidic chimeric antigen receptor T cell switches and uses thereof US20150307564. (2015).
[67]
Campana D, Imai C. Chimeric receptors with 4-1BB stimulatory signaling domain US20160009784. (2016).
[68]
Brogdon J, Choi E, Ebersbach HE, et al. Nucleic acid encoding a humanized anti-BCMA chimeric antigen receptor US20160046724. (2016).
[69]
Lim WA, Morsut L, Roybal KT. Binding-triggered transcriptional switches and methods of use thereof US20160264665. (2016).
[70]
Wang B, Zeiner G. Methods for making novel antigen binding domains US20170336393. (2017).
[71]
Li P, Lai Y, Lin S, Yao Y. Chimeric antigen receptor containing a toll-like receptor intracellular domain US20170233454. (2017).
[72]
Wang B, Zeiner G. Methods for making novel antigen binding domains US20170336393. (2017).
[73]
Jensen M. Bispecific chimeric antigen receptors and methods of use thereof to treat cancer US20170107285. (2017).
[74]
Mumm JB, Chan IH. Method of modulating a chimeric antigen receptor T cell immune response by administering IL-10 US20180207270. (2018).
[75]
DeGregorio MW. Methods for immunomodulation of cancer and infectious disease therapy US20180000747. (2018).
[76]
Lu J, Yang A, Liu C, et al. Antibody/T-cell receptor chimeric constructs and uses thereof US20180085457. (2018).

Rights & Permissions Print Cite
Article Metrics
67
6
© 2024 Bentham Science Publishers | Privacy Policy