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Annals of Hematology

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09.05.2020 | Review Article

Chimeric antigen receptor therapy in hematological malignancies: antigenic targets and their clinical research progress

verfasst von: Juanjuan Zhao, Meirong Wu, Zhifeng Li, Sheng Su, Yin Wen, Litian Zhang, Yuhua Li

Erschienen in: Annals of Hematology | Ausgabe 8/2020

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ABSTRACT

Chimeric antigen receptor (CAR)-based immunotherapy has achieved dramatic success in the treatment of B cell malignancies, based on the summary of current research data, and has shown good potential in early phase cancer clinical trials. Modified constructs are being optimized to recognize and destroy tumor cells more effectively. By targeting the proper B-lineage-specific antigens such as CD19 and CD20, adoptive immunotherapy has demonstrated promising clinical results and already plays a role in the treatment of several lymphoid malignancies, which highlights the importance of target selection for other CAR therapies. The high efficacy of CAR-T cells has resulted in the approval of anti-CD19-directed CAR-T cells for the treatment of B cell malignancies. In this review, we focus on the basic structure and current clinical application of CAR-T cells, detail the research progress of CAR-T for different antigenic targets in hematological malignancies, and further discuss the current barriers and proposed solutions, investigating the possible mechanisms of recurrence of CAR-T cell therapy. A summary of the paper is also given to overview as the prospects for this therapy.

Huang Q, Xia J, Wang L et al (2018) miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy. J Hematol Oncol 11:90. https://doi.org/10.1186/s13045-018-0600-x CrossRefPubMedPubMedCentral

Riccione K, Suryadevara CM, Snyder D, Cui X, Sampson JH, Sanchez-Perez L (2015) Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care. J Vis Exp 96:e52397. https://doi.org/10.3791/52397 CrossRef

Kochenderfer JN, Dudley ME, Feldman SA et al (2012) B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 118(12):2709–2720. https://doi.org/10.1182/blood-2011-10-384388 CrossRef

Porter DL, Levine BL, Kalos M, Bagg A, June CH (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365(8):725–733. https://doi.org/10.1056/NEJMoa1103849 CrossRefPubMedPubMedCentral

Knochelmann HM, Smith AS, Dwyer CJ, Wyatt MM, Mehrotra S, Paulos CM (2018) CAR T cells in solid tumors: blueprints for building effective therapies. Front Immunol 9:1740. https://doi.org/10.3389/fimmu.2018.01740 CrossRefPubMedPubMedCentral

Cheadle EJ, Gornall H, Baldan V, Hanson V, Hawkins RE, Gilham DE (2014) CAR T cells: driving the road from the laboratory to the clinic. Immunol Rev 257(1):91–106. https://doi.org/10.1111/imr.12126 CrossRefPubMed

Rodgers DT, Mazagova M, Hampton EN et al (2016) Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. P Natl Acad Sci USA 113(4):E459–E468. https://doi.org/10.1073/pnas.1524155113 CrossRef

Bridgeman JS, Hawkins RE, Hombach AA, Abken H, Gilham DE (2010) Building better chimeric antigen receptors for adoptive T cell therapy. Curr Gene Ther 10(2):77–90CrossRefPubMed

Riddell SR, Jensen MC, June CH (2013) Chimeric antigen receptor–modified T cells: clinical translation in stem cell transplantation and beyond. Biol Blood Marrow Transplant 19(1 Suppl):S2–S5. https://doi.org/10.1016/j.bbmt.2012.10.021 CrossRefPubMed

10.

Curran KJ, Pegram HJ, Brentjens RJ (2012) Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions. J Gene Med 14(6):405–415. https://doi.org/10.1002/jgm.2604 CrossRefPubMedPubMedCentral

11.

Maher J (2012) Immunotherapy of malignant disease using chimeric antigen receptor engrafted T cells. ISRN Oncol 2012:1–23. https://doi.org/10.5402/2012/278093 CrossRef

12.

Kalos M (2012) Muscle CARs and TcRs: turbo-charged technologies for the (T cell) masses. Cancer Immunol Immunother 61(1):127–135. https://doi.org/10.1007/s00262-011-1173-5 CrossRefPubMed

13.

Till BG, Jensen MC, Wang J et al (2008) Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 112(6):2261–2271. https://doi.org/10.1182/blood-2007-12-128843 CrossRefPubMedPubMedCentral

14.

Park JR, DiGiusto DL, Slovak M et al (2007) Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol Ther 15(4):825–833. https://doi.org/10.1038/sj.mt.6300104 CrossRefPubMed

15.

McGinley L (2017) First gene therapy — ‘a true living drug’ — on the cusp of FDA approval.

16.

O'Rourke DM, Nasrallah MP, Desai A et al (2017) A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med 9:eaaa0984. https://doi.org/10.1126/scitranslmed.aaa0984 CrossRefPubMedPubMedCentral

17.

Mohammed S, Sukumaran S, Bajgain P et al (2017) Improving chimeric antigen receptor-modified T cell function by reversing the immunosuppressive tumor microenvironment of pancreatic cancer. Mol Ther 25(1):249–258. https://doi.org/10.1016/j.ymthe.2016.10.016 CrossRefPubMedPubMedCentral

18.

Posey AD Jr, Schwab RD, Boesteanu AC et al (2016) Engineered CAR T cells targeting the cancer-associated TnGlycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity 44(6):1444–1454. https://doi.org/10.1016/j.immuni.2016.05.014 CrossRefPubMedPubMedCentral

19.

Ostrand-Rosenberg S, Fenselau C (2018) Myeloid-derived suppressor cells: immune-suppressive cells that impair antitumor immunity and are sculpted by their environment. J Immunol 200:422–431. https://doi.org/10.4049/jimmunol.1701019 CrossRefPubMed

20.

Davoodzadeh Gholami M, Kardar GA, Saeedi Y, Heydari S, Garssen J, Falak R (2017) Exhaustion of T lymphocytes in the tumor microenvironment: significance and effective mechanisms. Cell Immunol 322:1–14. https://doi.org/10.1016/j.cellimm.2017.10.002 CrossRefPubMed

21.

Davila ML, Riviere I, Wang X et al. (2014) Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 6(224): 224ra25. https://doi.org/10.1126/scitranslmed.3008226

22.

Brentjens RJ, Davila ML, Riviere I et al (2013) CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 5(177):177ra38. https://doi.org/10.1126/scitranslmed.3005930 CrossRefPubMedPubMedCentral

23.

Dias A, Kenderian SJ, Westin GF, Litzow MR (2016) Novel therapeutic strategies in acute lymphoblastic leukemia. Curr Hematol Malig Rep 11(4):253–264. https://doi.org/10.1007/s11899-016-0326-1 CrossRefPubMed

24.

Brentjens RJ, Rivière I, Park JH et al (2011) Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 118(18):4817–4828. https://doi.org/10.1182/blood-2011-04-348540 CrossRefPubMedPubMedCentral

25.

Park JH, Rivière I, Gonen M et al (2018) Long-term ollow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med 378(5):449–459. https://doi.org/10.1056/NEJMoa1709919 CrossRefPubMedPubMedCentral

26.

Grupp SA, Kalos M, Barrett D et al (2013) Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. N Engl J Med 368(16):1509–1518. https://doi.org/10.1056/NEJMoa1215134 CrossRefPubMedPubMedCentral

27.

Maude SL, Frey N, Shaw PA et al (2014) Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N Engl J Med 371(16):1507–1517. https://doi.org/10.1056/NEJMoa1407222 CrossRefPubMedPubMedCentral

28.

Grupp SA, Maude SL, Shaw PA et al (2015) Durable remissions in children with relapsed/refractory ALL treated with T cells engineered with a CD19-targeted chimeric antigen receptor (CTL019). Blood 126(23):681–681CrossRef

29.

Maude SL, Teachey DT, Rheingold SR et al. (2016) Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL

30.

Anwer F, Shaukat AA, Zahid U et al (2017) Donor origin CAR T cells: graft versus malignancy effect without GVHD, a systematic review. Immunotherapy 9(2):123–130. https://doi.org/10.2217/imt-2016-0127 CrossRefPubMedPubMedCentral

31.

Maude SL, Laetsch TW, Buechner J et al (2018) Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 378:439–448. https://doi.org/10.1056/NEJMoa1709866 CrossRefPubMedPubMedCentral

32.

Onea AS, Jazirehi AR (2016) CD19 chimeric antigen receptor (CD19 CAR)-redirected adoptive T-cell immunotherapy for the treatment of relapsed or refractory B-cell non-Hodgkin’s lymphomas. Am J Cancer Res 6(2):403–424PubMedPubMedCentral

33.

Theodossiou C, Schwarzenberger P (2002) Non-Hodgkin’s lymphomas. Clin Obstet Gynecol 45(3):820–829CrossRefPubMed

34.

Schuster SJ, Svoboda J, Chong EA et al (2017) Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med 377(26):2545–2554. https://doi.org/10.1056/NEJMoa1708566 CrossRefPubMedPubMedCentral

35.

Ghorashian S, Pule M, Amrolia P (2015) CD19 chimeric antigen receptor T cell therapy for haematological malignancies. Br J Haematol 169(4):463–478. https://doi.org/10.1111/bjh.13340 CrossRefPubMed

36.

Schuster SJ, Svoboda J, Nasta SD et al (2015) Sustained remissions following chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with relapsed or refractory CD19+ lymphomas. Blood 126(183)

37.

Schuster SJ, Svoboda J, Nasta SD et al (2016) Treatment with chimeric antigen receptor modified T cells directed against CD19 (CTL019) results in durable remissions in patients with relapsed or refractory diffuse large B cell lymphomas of germinal center and non-germinal center origin, “double hit” diffuse large B cell lymphomas, and transformed follicular to diffuse large B cell lymphomas. Blood 128(3026)

38.

Chong EA, Svoboda J, Nastaet SD et al (2016) Chimeric antigen receptor modified T cells directed against CD19 (CTL019) in patients with poor prognosis, relapsed or refractory CD19 + follicular lymphoma: prolonged remissions relative to antecedent therapy. Blood 128(1100)

39.

Lee DW, Kochenderfer JN, Stetler-Stevenson M et al (2015) T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385(9967):517–528. https://doi.org/10.1016/S0140-6736(14)61403-3 CrossRefPubMed

40.

Stephen J. Schuster, Michael R. Bishop, Constantine S. Tam et al. (2019) Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 380(1): 45-56. https://doi.org/10.1056/NEJMoa1804980

41.

Chavez JC, Bachmeier C, Kharfan-Dabaja MA (2019) CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Ther Adv Hematol 10:2040620719841581. https://doi.org/10.1177/2040620719841581

42.

Kochenderfer JN, Wilson WH, Janik JE et al (2010) Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 116(20):4099–4102. https://doi.org/10.1182/blood-2010-04-281931 CrossRefPubMedPubMedCentral

43.

Kochenderfer JN, Dudley ME, Kassim SH et al (2015) Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 33(6):540–549. https://doi.org/10.1200/JCO.2014.56.2025 CrossRefPubMed

44.

Locke FL, Neelapu SS, Bartlett NL et al (2017) Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther 25:285–295. https://doi.org/10.1016/j.ymthe.2016.10.020 CrossRefPubMedPubMedCentral

45.

Neelapu SS, Locke FL, Bartlett NL et al (2017) Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 377(26):2531–2544. https://doi.org/10.1056/NEJMoa1707447 CrossRefPubMedPubMedCentral

46.

Locke FL, Ghobadi A, Jacobson CA et al (2019) 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 20(1):31–42. https://doi.org/10.1016/S1470-2045(18)30864-7 CrossRefPubMed

47.

Nastoupil LJ, Jain MD, Spiegel JY et al (2018) Axicabtagene ciloleucel (axi-cel) CD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory large B-cell lymphoma: real world experience. Blood 132:91CrossRef

48.

Jacobson CA, Hunter B, Armand P et al (2018) Axicabtagene ciloleucel in the real world: outcomes and predictors of response, resistance and toxicity. Blood 132:92CrossRef

49.

Sommermeyer D, Hudecek M, Kosasih PL et al (2016) Chimeric antigen receptormodified T cells derived from defined CD8 + and CD4 + subsets confer superior antitumor reactivity in vivo. Leukemia 30:492–500CrossRefPubMed

50.

Turtle CJ, Hanafi L, Berger C et al (2016) Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8 + and CD4 + CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med 8:355ra116. https://doi.org/10.1126/scitranslmed.aaf8621 CrossRefPubMedPubMedCentral

51.

B-Abramson JS, Palomba ML, Gordon LI et al (2017) CR rates in relapsed/refractory (R/R) aggressive NHL treated with the CD19-directed CAR T-cell product JCAR017 (TRANSCEND NHL 001). Am Soc Clin Oncol 35:7513–7513CrossRef

52.

Abramson JS, Palomba ML, Gordon LI et al (2017) High durable CR rates in relapsed/refractory (R/R) aggressive B-NHL treated with the CD19-directed CAR T cell product JCAR017 (TRANSCEND NHL 001): defined composition allows for dose-finding and definition of pivotal cohort. Blood 130(Suppl. 1):581

53.

Abramson J, Palomba ML, Gordon L et al (2017) High CR rates in relapsed/refractory (R/R) aggressive B-NHL treated with the CD19-directed CAR T cell product JCAR017 (TRANSCEND NHL 001). Hematol Oncol 35:138CrossRef

54.

Maloney DG, Abramson JS, Palomba ML et al (2017) Preliminary safety profile of the CD19-directed defined composition CAR T cell product JCAR017 in relapsed/refractory aggressive B-NHL patients: potential for outpatient administration. Blood 130(Suppl. 1):1552

55.

Abramson JS, Gordon LI, Palomba ML et al (2011) Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL. J Clin Oncol abstract 7505

56.

Savoldo B, Ramos CA, Liu E et al (2011) CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 121(5):1822–1826. https://doi.org/10.1172/JCI46110 CrossRefPubMedPubMedCentral

57.

Kochenderfer JN, Dudley ME, Carpenter RO et al (2013) Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 122(25):4129–4139. https://doi.org/10.1182/blood CrossRefPubMedPubMedCentral

58.

Rai KR, Jain P (2016) Chronic lymphocytic leukemia (CLL)-Then and now. Am J Hematol 91(3):330–340. https://doi.org/10.1002/ajh.24282 CrossRefPubMed

59.

Hosing C, Kebriaei P, Wierda W, Jena B, Cooper LJN, Shpall E (2013) CARs in chronic lymphocytic leukemia – ready to drive. Curr Hematol Malig Rep 8(1):60–70. https://doi.org/10.1007/s11899-012-0145-y CrossRefPubMed

60.

Kowolik CM, Topp MS, Gonzalez S et al (2006) CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res 66:10995–11004. https://doi.org/10.1158/0008-5472.CAN-06-0160 CrossRefPubMed

61.

Kalos M, Levine BL, Porter DL et al (2011) T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 3(95):95ra73. https://doi.org/10.1126/scitranslmed.3002842 CrossRefPubMedPubMedCentral

62.

Kochenderfer JN, Dudley ME, Feldman SA et al (2012) B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119:2709–2720. https://doi.org/10.1182/blood-2011-10-384388 CrossRefPubMedPubMedCentral

63.

Porter DL, Hwang W, Frey NV et al (2015) Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med 7(303):303ra139. https://doi.org/10.1126/scitranslmed.aac5415 CrossRefPubMedPubMedCentral

64.

Fraietta JA, Lacey SF, Orlando EJ et al (2018) Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 24(5):563–571. https://doi.org/10.1038/s41591-018-0010-1 CrossRefPubMedPubMedCentral

65.

Non-Hodgkin’s Lymphoma Classification Project (1997) A clinical evaluation of the international lymphoma study group classification of non-Hodgkin’s lymphoma. Blood 89:3909–3918CrossRef

66.

Jabbour E, Pui CH, Kantarjian H (2018) Progress and innovations in the management of adult acute lymphoblastic leukemia. Jama Oncol 4(10):1413–1420. https://doi.org/10.1001/jamaoncol.2018.1915 CrossRefPubMed

67.

Till BG, Jensen MC, Wang J et al (2012) CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood 119(17):3940–3950. https://doi.org/10.1182/blood-2011-10-387969 CrossRefPubMedPubMedCentral

68.

Wang Y, Zhang WY, Han QW et al (2014) Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol 155(2):160–175. https://doi.org/10.1016/j.clim.2014.10.002 CrossRefPubMed

69.

Klausen U, Jørgensen NGD, Grauslund JH, Holmström MO, Andersen MH (2019) Cancer immune therapy for lymphoid malignancies: recent advances. Semin Immunopathol 41(1):111–124. https://doi.org/10.1007/s00281-018-0696-7 CrossRefPubMed

70.

Schneider D, Xiong Y, Wu D et al (2017) A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines. J ImmunoTher Cancer 5:42. https://doi.org/10.1186/s40425-017-0246-1 CrossRefPubMedPubMedCentral

71.

Martyniszyn A, Krahl AC, André MC, Hombach AA, Abken H (2017) CD20-CD19 bispecific CAR T cells for the treatment of B-cell malignancies. Hum Gene Ther 28(12):1147–1157. https://doi.org/10.1089/hum.2017.126 CrossRefPubMed

72.

Sullivan-Chang L, RT OD, Tuscano JM (2013) Targeting CD22 in B-cell malignancies: current status and clinical outlook. Biodrugs 27(4):293–304. https://doi.org/10.1007/s40259-013-0016-7 CrossRefPubMed

73.

Zhen A, Peterson CW, Carrillo MA et al (2017) Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS. PLoS Pathog 13(12):1006753. https://doi.org/10.1371/journal.ppat.1006753 CrossRef

74.

Smith TT, Moffett HF, Stephan SB et al (2017) Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors. J Clin Invest 127(6):2176–2191. https://doi.org/10.1172/JCI87624 CrossRefPubMedPubMedCentral

75.

Thistlethwaite FC, Gilham DE, Guest RD et al (2017) 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 66(11):1425–1436. https://doi.org/10.1007/s00262-017-2034-7 CrossRefPubMedPubMedCentral

76.

Feng K, Guo Y, Dai H, Wang Y, Li X, Jia H, Han W (2016) Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Sci China Life Sci 59(5):468–479. https://doi.org/10.1007/s11427-016-5023-8 CrossRefPubMed

77.

Lamers CH, Klaver Y, Gratama JW, Sleijfer S, Debets R (2016) Treatment of metastatic renal cell carcinoma (mRCC) with CAIX CAR-engineered T-cells-a completed study overview. Biochem Soc Trans 44(3):951–959. https://doi.org/10.1042/BST20160037 CrossRefPubMed

78.

Beatty GL, Haas AR, Maus MV et al (2014) Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce antitumor activity in solid malignancies. Cancer Immunol Res 2(2):112–120. https://doi.org/10.1158/2326-6066.CIR-13-0170 CrossRefPubMed

79.

Haso W, Lee DW, Shah NN et al (2013) Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood 121(7):1165–1174. https://doi.org/10.1182/blood-2012-06 CrossRefPubMedPubMedCentral

80.

Fry TJ, Shah NN, Orentas RJ et al (2017) CD22-targeted CAR T cells induce remission in B-ALL that i naive or resistant to CD19-targeted CAR immunotherapy. Nat Med 24(1):20–28. https://doi.org/10.1038/nm.4441 CrossRefPubMedPubMedCentral

81.

Ramos CA, Ballard B, Zhang H et al (2017) Clinical and immunological responses after CD30-specific chimeric antigen receptor–redirected lymphocytes. J Clin Invest 127(9):3462–3471. https://doi.org/10.1172/JCI94306 CrossRefPubMedPubMedCentral

82.

Pierce JM, Mehta A (2017) Diagnostic, prognostic and therapeutic role of CD30 in lymphoma. Expert Rev Hematol 10(1):29–37. https://doi.org/10.1080/17474086.2017.1270202 CrossRefPubMed

83.

Wang CM, Wu ZQ, Wang Y et al (2017) Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res 23(5):1156–1166. https://doi.org/10.1158/1078-0432.CCR-16-1365 CrossRefPubMed

84.

Zheng W, O'Hear CE, Alli R et al (2018) PI3K orchestration of the in vivo persistence of chimeric antigen receptor-modified T cells. Leukemia 32(1):157–1167. https://doi.org/10.1038/s41375-017-0008-6 CrossRef

85.

Wang QS, Wang Y, Lv HY et al (2015) Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther 23(1):184–191. https://doi.org/10.1038/mt.2014.164 CrossRefPubMed

86.

Kenderian SS, Ruella M, Shestova O et al (2015) CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. Leukemia 29(8):1637–1647. https://doi.org/10.1038/leu.2015.52 CrossRefPubMedPubMedCentral

87.

Pizzitola I, Anjos-Afonso F, Rouault-Pierre K et al (2014) Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia 28(8):1596–1605. https://doi.org/10.1038/leu.2014.62 CrossRefPubMed

88.

Dutour A, Marin V, Pizzitola I et al (2012) In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD33 acute myeloid leukemia. Adv Hematol 2012:683065. https://doi.org/10.1155/2012/683065 CrossRefPubMedPubMedCentral

89.

Marin V, Pizzitola I, Agostoni V et al (2010) Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors. Haematologica 95(12):2144–2152. https://doi.org/10.3324/haematol.2010.026310 CrossRefPubMedPubMedCentral

90.

Larson RA, Sievers EL, Stadtmauer EA et al (2005) Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 104(7):1442–1452. https://doi.org/10.1002/cncr.21326 CrossRefPubMed

91.

McKoy JM, Angelotta C, Bennett CL et al (2007) Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project. Leuk Res 31(5):599–604. https://doi.org/10.1016/j.leukres.2006.07.005 CrossRefPubMed

92.

Li S, Tao Z, Xu Y et al (2018) CD33-specific chimeric antigen receptor T cells with different co-stimulators showed potent anti-leukemia efficacy and different phenotype. Hum Gene Ther 29(5):626–639. https://doi.org/10.1089/hum.2017.241 CrossRefPubMed

93.

Cartellieri M, Feldmann A, Koristka S et al (2016) Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts. Blood Cancer J 6(8):e458. https://doi.org/10.1038/bcj.2016.61 CrossRefPubMedPubMedCentral

94.

Kim MY, Yu KR, Kenderian SS et al (2018) Genetic inactivation of CD33 in hematopoietic stem cells to enable CAR T cell immunotherapy for acute myeloid leukemia. Cell 173(6):1439–1453.e19. https://doi.org/10.1016/j.cell.2018.05.013 CrossRefPubMedPubMedCentral

95.

Tang X, Yang L, Li Z et al (2018) First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Am J Cancer Res 8(6):1083–1089PubMedPubMedCentral

96.

Jordan CT, Upchurch D, Szilvassy SJ et al (2000) The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 14(10):1777–1784CrossRefPubMed

97.

Hwang K, Park CJ, Jang S et al (2013) Immunohistochemical analysis of CD123, CD56 and CD4 for the diagnosis of minimal bone marrow involvement by blastic plasmacytoid dendritic cell neoplasm. Histopathology 62(5):764–770. https://doi.org/10.1111/his.12079 CrossRefPubMed

98.

Frankel AE, Woo JH, Ahn C et al (2014) Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. Blood 124(3):385–392. https://doi.org/10.1182/blood-2014-04-566737 CrossRefPubMedPubMedCentral

99.

Mardiros A, Dos Santos C, McDonald T et al (2013) T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood 122(18):3138–3148. https://doi.org/10.1182/blood-2012-12-474056 CrossRefPubMedPubMedCentral

100.

Hope KJ, Jin L, Dick JE (2004) Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 5(7):738–743. https://doi.org/10.1038/ni1080 CrossRefPubMed

101.

Casucci M, Nicolis di Robilant B, Falcone L et al (2013) CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 122(20):3461–3472. https://doi.org/10.1182/blood-2013-04-493361 CrossRefPubMed

102.

Petrov JC, Wada M, Pinz KG et al (2018) Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. Leukemia 32(6):1317–1326. https://doi.org/10.1038/s41375-018-0075-3 CrossRefPubMedPubMedCentral

103.

Stillwell R, Bierer BE (2001) T cell signal transduction and the role of CD7 in costimulation. Immunol Res 24(1):31–52CrossRefPubMed

104.

Mayer KE, Mall S, Yusufi N et al (2018) T-cell functionality testing is highly relevant to developing novel immuno-tracers monitoring T cells in the context of immunotherapies and revealed CD7 as an attractive target. Theranostics 8(21):6070–6087. https://doi.org/10.7150/thno.27275 CrossRefPubMedPubMedCentral

105.

Rabinowich H, Pricop L, Herberman RB, Whiteside TL (1994) Expression and function of CD7 molecule on human natural killer cells. J Immunol 152(2):517–526PubMed

106.

Campana D, van Dongen JJ, Mehta A et al (1991) Stages of T-cell receptor protein expression in T-cell acute lymphoblastic leukemia. Blood 77(7):1546–1554CrossRefPubMed

107.

Lee DM, Staats HF, Sundy JS et al. (1998) Immunologic characterization of CD7-deficient mice. J Immunol 160(12): 5749-5756.

108.

Bonilla FA, Kokron CM, Swinton P, Geha RS (1997) Targeted gene disruption of murine CD7. Int Immunol 9(12):1875–1883CrossRefPubMed

109.

Frankel AE, Laver JH, Willingham MC, Burns LJ, Kersey JH, Vallera DA (1997) Therapy of patients with T-cell lymphomas and leukemias using an anti-CD7 monoclonal antibody-rich a chain immunotoxin. Leuk Lymphoma 26(3-4):287–298CrossRefPubMed

110.

Flavell DJ, Holmes SE, Warnes SL, Flavell SU (2019) The TLR3 agonist poly inosinic: cytidylic acid significantly augments the therapeutic activity of an anti-CD7 immunotoxin for human T-cell leukaemia. Biomedicines 7(1):E13. https://doi.org/10.3390/biomedicines7010013 CrossRefPubMed

111.

Gomes-Silva D, Srinivasan M, Sharma S et al (2019) CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood 130(3):285–296. https://doi.org/10.1182/blood-2017-01-761320 CrossRef

112.

Png YT, Vinanica N, Kamiya T, Shimasaki N, Coustan-Smith E, Campana D (2019) Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. Blood Adv 1(25):2348–2360. https://doi.org/10.1182/bloodadvances.2017009928 CrossRef

113.

You F, Wang Y, Jiang L et al (2019) A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia. Am J Cancer Res 9(1):64–78PubMedPubMedCentral

114.

Small D, Levenstein M, Kim E et al (1994) STK-1, the human homolog of Flk-2/Flt-3, is selectively expressed in CD34+ human bone marrow cells and is involved in the proliferation of early progenitor/stem cells. Proc Natl Acad Sci U S A 91(2):459–463CrossRefPubMedPubMedCentral

115.

Gilliland DG, Griffin JD (2002) The roles of FLT3 in hematopoiesis and leukemia. Blood 100(5):1532–1542CrossRefPubMed

116.

Kottaridis PD, Gale RE, Frew ME et al (2001) The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 98(6):1752–1759CrossRefPubMed

117.

Fathi AT, Chen YB (2017) The role of FLT3 inhibitors in the treatment of FLT3-mutated acute myeloid leukemia. Eur J Haematol 98(4):330–336. https://doi.org/10.1111/ejh.12841 CrossRefPubMed

118.

Taylor SJ, Duyvestyn JM, Dagger SA et al (2017) Preventing chemotherapy-induced myelosuppression by repurposing the FLT3 inhibitor quizartinib. Sci Transl Med 9(402):eaam8060. https://doi.org/10.1126/scitranslmed.aam8060 CrossRefPubMed

119.

Döhner H, Weisdorf DJ, Bloomfield CD (2015) Acute myeloid leukemia. N Engl J Med 373(12):1136–1152. https://doi.org/10.1056/NEJMra1406184 CrossRefPubMed

120.

Kindler T, Lipka DB, Fischer T (2010) FLT3 as a therapeutic target in AML: still challenging after all these years. Blood 116(24):5089–5102. https://doi.org/10.1182/blood-2010-04-261867 CrossRefPubMed

121.

Louise M. Kelly, Qing Liu, Jeffrey L. Kutok et al. (2002) FLT3 internal tandem duplication mutations associated with human acute myeloid leukemias induce myelo proliferative disease in a murine bone marrow transplant model. Blood 99: 310. https://doi.org/10.1182/blood.V99.1.310

122.

Stone RM, Mandrekar SJ, Sanford BL et al (2017) Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 377(5):454–464. https://doi.org/10.1056/NEJMoa1614359 CrossRefPubMedPubMedCentral

123.

Chen L, Mao H, Zhang J et al (2017) Targeting FLT3 by chimeric antigen receptor T cells for the treatment of acute myeloid leukemia. Leukemia 31(8):1830–1834. https://doi.org/10.1038/leu.2017.147 CrossRefPubMedPubMedCentral

124.

Wang Y, Xu Y, Li S et al (2018) Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells. J Hematol Oncol 11(1):60. https://doi.org/10.1186/s13045-018-0603-7 CrossRefPubMedPubMedCentral

125.

Quarona V, Zaccarello G, Chillemi A et al (2013) CD38 and CD157: a long journey from activation markers to multifunctional molecules. Cytometry B Clin Cytom 84(4):207–217. https://doi.org/10.1002/cyto.b.21092 CrossRefPubMed

126.

Drent E, Themeli M, Poels R et al (2017) A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Mol Ther 25(8):1946–1958. https://doi.org/10.1016/j.ymthe.2017.04.024 CrossRefPubMedPubMedCentral

127.

Mele S, Devereux S, Pepper AG, Infante E, Ridley AJ (2018) Calcium-RasGRP2-Rap1 signaling mediates CD38-induced migration of chronic lymphocytic leukemia cells. Blood advances 2(13):1551–1561. https://doi.org/10.1182/bloodadvances.2017014506 CrossRefPubMedPubMedCentral

128.

Palumbo A, Chanan-Khan A, Weisel K et al (2014) Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 375(8):754–766. https://doi.org/10.1056/NEJMoa1606038 CrossRef

129.

Facon T, Kumar S, Plesner T et al (2019) Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med 380(22):2104–2115. https://doi.org/10.1056/NEJMoa1817249 CrossRefPubMed

130.

Mihara K, Yanagihara K, Takigahira M et al (2009) Activated T – cell-mediated immunotherapy with a cxhimeric receptor against CD38 in B-cell non-Hodgkin lymphoma. J Immunother 32(7):737–743. https://doi.org/10.1097/CJI.0b013e3181adaff1 CrossRefPubMed

131.

Mihara K, Yanagihara K, Takigahira M et al (2010) Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma. Br J Haematol 151(1):37–46. https://doi.org/10.1111/j.1365-2141.2010.08297.x CrossRefPubMed

132.

Drent E, Groen RW, Noort WA et al (2016) Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica 101(5):616–625. https://doi.org/10.3324/haematol.2015.137620 CrossRefPubMedPubMedCentral

133.

Drent E, Poels R, Mulders MJ et al (2018) Feasibility of controlling CD38-CAR T cell activity with a Tet-on inducible CAR design. PLoS One 13(5):e0197349. https://doi.org/10.1371/journal.pone.0197349 CrossRefPubMedPubMedCentral

134.

Feng X, Zhang L, Acharya C et al (2017) Targeting CD38 suppresses induction and function of T regulatory cells to mitigate immunosuppression in multiple myeloma. Clin Cancer Res 23(15):4290–4300. https://doi.org/10.1158/1078-0432.CCR-16-3192 CrossRefPubMedPubMedCentral

135.

Rickert RC, Jellusova J, Miletic AV (2011) Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev 244(1):115–133. https://doi.org/10.1111/j.1600-065X.2011.01067.x CrossRefPubMedPubMedCentral

136.

Jennifer N. Brudno, Irina Maric, Steven D. Hartman et al. (2018) T cells genetically modified to express an anti–B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol 36(22): 2267-2280. https://doi.org/10.1200/JCO.2018.77.8084.

137.

Carpenter RO, Evbuomwan MO, Pittaluga S et al (2013) B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res 19(8):2048–2060. https://doi.org/10.1158/1078-0432.CCR-12-2422 CrossRefPubMedPubMedCentral

138.

Hudecek M, Einsele H (2016) Myeloma CARs are rolling into the clinical arena. Blood 128(13):1667–1668. https://doi.org/10.1182/blood-2016-08-729467 CrossRefPubMed

139.

Brudno JN, Maric I, Hartman SD et al (2018) T cells genetically modified to express an anti – B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol 36(22):2267–2280. https://doi.org/10.1200/JCO.2018.77.8084 CrossRefPubMedPubMedCentral

140.

Appelbaum JS, Milano F (2018) Hematopoietic stem cell transplantation in the era of engineered cell therapy. Curr Hematol Malig Rep 13(6):484–493. https://doi.org/10.1007/s11899-018-0476-4 CrossRefPubMedPubMedCentral

141.

Berahovich R, Zhou H, Xu S et al (2018) CAR-T cells based on novel BCMA monoclonal antibody block multiple myeloma cell growth. Cancers 10(9):323. https://doi.org/10.3390/cancers10090323 CrossRefPubMedCentral

142.

Teitz-Tennenbaum S, Li Q, Davis M et al (2009) Radiotherapy combined with intratumoral dendritic cell vaccination enhances the therapeutic efficacy of adoptive T-cell transfer. J Immunother 32(6):602–612. https://doi.org/10.1097/CJI.0b013e3181a95165 CrossRefPubMedPubMedCentral

143.

Eric A. Reits, James W. Hodge, Carla A. Herberts et al. (2006) Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med 203 (5) : 1259-1271. https://doi.org/10.1084/jem.20052494

144.

Koike N, Pilon-Thomas S, Mulé J et al (2008) Nonmyeloablative chemotherapy followed by T-cell adoptive transfer and dendritic cell-based vaccination results in rejection of established melanoma. J Immunother 31(4):402–412. https://doi.org/10.1097/CJI.0b013e31816cabbb CrossRefPubMed

145.

Dudley ME, Wunderlich JR, Yang JC et al (2005) Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 23(10):2346–2357. https://doi.org/10.1200/JCO.2005.00.240 CrossRefPubMed

146.

Chen N, Morello A, Tano Z et al (2017) CAR T-cell intrinsic PD-1 checkpoint blockade: a two-in-one approach for solid tumor immunotherapy. OncoImmunology 6(2):e1273302. https://doi.org/10.1080/2162402X CrossRefPubMed

147.

John LB, Devaud C, Duong CP et al (2013) Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 19(20):5636–5646. https://doi.org/10.1158/1078-0432.CCR-13-0458 CrossRefPubMed

148.

Cherkassky L, Morello A, Villena-Vargas J et al (2016) Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Investig 126(8):3130–3144. https://doi.org/10.1172/JCI83092 CrossRefPubMedPubMedCentral

149.

Ma Y, Zhang L, Huang X (2014) Genome modification by CRISPR/Cas9. FEBS J 281(23):5186–5193. https://doi.org/10.1111/febs.13110 CrossRefPubMed

150.

Rupp LJ, Schumann K, Roybal KT et al (2017) CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Sci Rep 7(1):737. https://doi.org/10.1038/s41598-017-00462-8 CrossRefPubMedPubMedCentral

151.

Ajina A, Maher J (2017) Prospects for combined use of oncolytic viruses and CAR T-cells. J Immunother Cancer 5(1):90. https://doi.org/10.1186/s40425-017-0294-6

152.

Sampath P, Thorne SH (2015) Novel therapeutic strategies in human malignancy:combining immunotherapy and oncolytic virotherapy. Oncolytic Virother 4:75–82. https://doi.org/10.2147/OV.S54738

153.

Twumasi-Boateng K, Pettigrew JL, Kwok YYE, Bell JC, Nelson BH (2018) Oncolytic viruses as engineering platforms for combination immunotherapy. Nat Rev Cancer 18(7):419–432. https://doi.org/10.1038/s41568-018-0009-4 CrossRefPubMed

154.

Wing A, Fajardo CA, Posey AD Jr et al (2018) Improving CART-Cell therapy of solid tumors with oncolytic virus–driven production of a bispecific T-cell engager. Cancer Immunol Res 6(5):605–616. https://doi.org/10.1158/2326-6066.CIR-17-0314

155.

Hendriks RW, Yuvaraj S, Kil LP (2014) Targeting Bruton’s tyrosine kinase in B cell malignancies. Nat Rev Cancer 14(4):219–232. https://doi.org/10.1038/nrc3702 CrossRefPubMed

156.

Deeks ED (2017) Ibrutinib: a review in chronic lymphocytic leukaemia. Drugs 77(2):225–236. https://doi.org/10.1007/s40265-017-0695-3 CrossRefPubMed

157.

Ruella M, Kenderian SS, Shestova O et al (2016) The addition of the BTK inhibitor ibrutinib to anti-CD19 chimeric antigen receptor T cells (CART19) improves responses against mantle cell lymphoma. Clin Cancer Res 22(11):2684–2696. https://doi.org/10.1158/1078-0432.CCR-15-1527 CrossRefPubMed

158.

Lee DW, Santomasso BD, Locke FL et al (2019) ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 25(4):625–638. https://doi.org/10.1016/j.bbmt.2018.12.758 CrossRefPubMed

159.

CAR T-Cell Therapy: A Healthcare Professional's Guide - Adverse Events. 2017. https://www.drugs.com/slideshow/car-t-cell-therapy-a-healthcare-professional-s-guide-adverse-events-1278

160.

Rubin DB, Danish HH, Ali AB et al (2019) Neurological toxicities associated with chimeric antigen receptor T-cell therapy. Brain 142(5):1334–1348. https://doi.org/10.1093/brain/awz053 CrossRefPubMed

161.

Hirayama AV, Turtle CJ (2019) Toxicities of CD19 CAR-T cell immunotherapy. Am J Hematol 94(S1):S42–S49. https://doi.org/10.1002/ajh.25445 CrossRefPubMed

162.

Perrinjaquet C, Desbaillets N, Hottinger AF (2019) Neurotoxicity associated with cancer immunotherapy: immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy. Curr Opin Neurol 32(3):500–510. https://doi.org/10.1097/WCO.0000000000000686 CrossRefPubMed

163.

Hay KA (2018) Cytokine release syndrome and neurotoxicity after CD19 chimeric antigen receptor-modified (CAR-) T cell therapy. Br J Haematol 183(3):364–374. https://doi.org/10.1111/bjh.15644

164.

Jaspers JE, Brentjens RJ (2017) Development of CAR T cells designed to improve antitumor efficacy and safety. Pharmacol Therapeut 178:83–91. https://doi.org/10.1016/j.pharmthera.2017.03.012 CrossRef

165.

Lock D, Mockel-Tenbrinck N, Drechsel K et al (2017) Automated manufacturing of potent CD20-directed chimeric antigen receptor T cells for clinical use. Hum Gene Ther 28(10):914–925. https://doi.org/10.1089/hum.2017.111 CrossRefPubMed

166.

Blaeschke F, Stenger D, Kaeuferle T et al (2018) Induction of a central memory and stem cell memory phenotype in functionally active CD4+ and CD8+ CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19+ acute lymphoblastic leukemia. Cancer Immunol Immunother 67(7):1053–1066. https://doi.org/10.1007/s00262-018-2155-7 CrossRefPubMed

167.

Gattinoni L, Lugli E, Ji Y et al (2011) A human memory T cell subset with stem cell–like properties. Nat Med 17(10):1290–1297. https://doi.org/10.1038/nm.2446 CrossRefPubMedPubMedCentral

168.

Zanon V, Pilipow K, Scamardella E et al (2017) Curtailed T-cell activation curbs effector differentiation and generates CD8+ T cells with a naturally-occurring memory stem cell phenotype. Eur J Immunol 47(9):1468–1476. https://doi.org/10.1002/eji.201646732 CrossRefPubMedPubMedCentral

169.

Hurton LV, Singh H, Najjar AM et al (2016) Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells. Proc Natl Acad Sci U S A 113(48):7788–7797. https://doi.org/10.1073/pnas.1610544113 CrossRef

170.

Xu Y, Zhang M, Ramos CA et al (2014) Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood 123(24):3750–3759. https://doi.org/10.1182/blood-2014-01-552174 CrossRefPubMedPubMedCentral

171.

Xu XJ, Song DG, Poussin M et al (2016) Multiparameter comparative analysis reveals differential impacts of various cytokines on CART cell phenotype and function ex vivo and in vivo. Oncotarget 7(50):82354–82368. https://doi.org/10.18632/oncotarget.10510 CrossRefPubMedPubMedCentral

172.

Zhang X, Lv X, Song Y (2018) Short-term culture with IL-2 is beneficial for potent memory chimeric antigen receptor T cell production. Biochem Biophys Res Commun 495(2):1833–1838. https://doi.org/10.1016/j.bbrc.2017.12.041 CrossRefPubMed

173.

Kaartinen T, Luostarinen A, Maliniemi P et al (2017) Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion. Cytotherapy 19(6):689–702. https://doi.org/10.1016/j.jcyt.2017.03.067 CrossRefPubMed

174.

Gattinoni L, Klebanoff CA, Restifo NP (2012) Paths to stemness: building the ultimate antitumour T cell. Nat Rev Cancer 12(10):671–684. https://doi.org/10.1038/nrc3322 CrossRefPubMedPubMedCentral

175.

Viardot A, Wais V, Sala E et al (2019) Chimeric antigen receptor (CAR) T-cell therapy as a treatment option for patients with B-cell lymphomas: perspectives on the therapeutic potential of axicabtagene ciloleucel. Cancer Manag Res 11:2393–2404. https://doi.org/10.2147/CMAR.S163225 CrossRefPubMedPubMedCentral

176.

Drent E, Poels R, Ruiter R et al (2019) Combined CD28 and 4-1BB costimulation potentiates affinity-tuned chimeric antigen receptor-engineered T cells. Clin Cancer Res 25:1078–0432. https://doi.org/10.1158/1078-0432.CCR-18-2559 CrossRef

177.

Gargett T, Brown MP (2014) Different cytokine and stimulation conditions influence the expansion and immune phenotype of third-generation chimeric antigen receptor T cells specific for tumor antigen GD2. Cytotherapy 17(4):487–495. https://doi.org/10.1016/j.jcyt.2014.12.002

178.

Suryadevara CM, Desai R, Farber SH et al (2019) Preventing Lck activation in CAR T cells confers Treg resistance but requires 4-1BB signaling for them to persist and treat solid tumors in nonlymphodepleted hosts. Clin Cancer Res 25(1):358–368. https://doi.org/10.1158/1078-0432.CCR-18-1211 CrossRefPubMed

179.

Wang X, Walter M, Urak R et al (2018) Lenalidomide enhances the function of CS1 chimeric antigen receptor–redirected T cells against multiple myeloma. Clin Cancer Res 24(1):106–119. https://doi.org/10.1158/1078-0432.CCR-17-0344 CrossRefPubMed

180.

Klebanoff CA, Crompton JG, Leonardi AJ et al (2017) Inhibition of AKT signaling uncouples T cell differentiation from expansion for receptor-engineered adoptive immunotherapy. JCI Insight 2(23):95103. https://doi.org/10.1172/jci.insight.95103 CrossRefPubMed

181.

Karlsson H, Lindqvist AC, Fransson M et al (2013) Combining CAR T cells and the Bcl-2 family apoptosis inhibitor ABT-737 for treating B-cell malignancy. Cancer Gene Ther 20(7):386–393. https://doi.org/10.1038/cgt.2013.35 CrossRefPubMed

182.

Ghassemi S, Nunez-Cruz S, O'Connor RS et al (2018) Reducing ex vivo culture improves the antileukemic activity of chimeric antigen receptor (CAR) T cells. Cancer Immunol Res 6(9):1100–1109. https://doi.org/10.1158/2326-6066.CIR-17-0405 CrossRefPubMedPubMedCentral

183.

Orlando EJ, Han X, Tribouley C et al (2018) Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat Med 24(10):1504–1506. https://doi.org/10.1038/s41591-018-0146-z CrossRefPubMed

184.

Arita A, McFarland DC, Myklebust JH et al (2013) Signaling pathways in lymphoma: pathogenesis and therapeutic targets. Future Oncol 9:1549–1571. https://doi.org/10.2217/FON.13.113 CrossRefPubMed

185.

Kang MH, Reynolds CP (2009) Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res 15(4):1126–1132. https://doi.org/10.1158/1078-0432.CCR-08-0144 CrossRefPubMedPubMedCentral

186.

Yunis JJ, Mayer MG, Arnesen MA, Aeppli DP, Oken MM, Frizzera G (1989) Bcl-2 and other genomic alterations in the prognosis of large-cell lymphoma. N Engl J Med 320(16):1047–1054. https://doi.org/10.1056/NEJM198904203201605 CrossRefPubMed

Titel: Chimeric antigen receptor therapy in hematological malignancies: antigenic targets and their clinical research progress
verfasst von: Juanjuan Zhao
Meirong Wu
Zhifeng Li
Sheng Su
Yin Wen
Litian Zhang
Yuhua Li
Publikationsdatum: 09.05.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 8/2020
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-020-04020-7

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