Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts

Blood Cancer Journal

Volumn 6, Issue 8, 2016, Pages

  Cartellieri, M ^a,b   Feldmann, A ^a,c   Koristka, S ^a,c   Arndt, C ^a,c   Loff, S ^a,d   Ehninger, A ^d   von Bonin, M ^a   Bejestani, E P ^a   Ehninger, G ^a   Bachmann, M P ^a,c  

^a UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^b Cellex Patient Treatment GmbH   (Germany)

^c INSTITUTE OF ION BEAM PHYSICS AND MATERIALS RESEARCH   (Germany)

^d GEMoaB Monoclonals GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD123 ANTIGEN; CD19-SPECIFIC CHIMERIC ANTIGEN RECEPTOR; CD33 ANTIGEN; CD33 PROTEIN, HUMAN; CYTOKINE; LYMPHOCYTE ANTIGEN RECEPTOR; TUMOR ANTIGEN;

ACUTE MYELOID LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; ANIMAL; CYTOTOXICITY; DISEASE MODEL; GENE EXPRESSION REGULATION; GENE VECTOR; GENETIC TRANSDUCTION; GENETICS; HUMAN; IMMUNOLOGY; KNOCKOUT MOUSE; LENTIVIRINAE; METABOLISM; MOUSE; PATHOLOGY; PROCEDURES; T LYMPHOCYTE; TUMOR VOLUME;

ANIMALS; ANTIGENS, NEOPLASM; CYTOKINES; CYTOTOXICITY, IMMUNOLOGIC; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION; GENETIC VECTORS; HUMANS; IMMUNOTHERAPY, ADOPTIVE; INTERLEUKIN-3 RECEPTOR ALPHA SUBUNIT; LENTIVIRUS; LEUKEMIA, MYELOID, ACUTE; MICE; MICE, KNOCKOUT; RECEPTORS, ANTIGEN, T-CELL; SIALIC ACID BINDING IG-LIKE LECTIN 3; T-LYMPHOCYTES; TRANSDUCTION, GENETIC; TUMOR BURDEN;

EID: 85019121172     PISSN: None     EISSN: 20445385     Source Type: Journal    
DOI: 10.1038/BCJ.2016.61     Document Type: Article

References (46)

1. Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapyrefractory acute lymphoblastic leukemia. Sci Transl Med 2013; 5: 177ra38.
2. Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I et al. 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 2012; 119: 2709–2720.
3. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA et al. 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: 517–528.
4. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014; 371: 1507–1517.
5. Cartellieri M, Bachmann M, Feldmann A, Bippes C, Stamova S, Wehner R et al. Chimeric antigen receptor-engineered T cells for immunotherapy of cancer. J Biomed Biotechnol 2010; 5: 956304.
6. Topfer K, Kempe S, Muller N, Schmitz M, Bachmann M, Cartellieri M et al. Tumor evasion from T cell surveillance. J Biomed Biotechnol 2011; 2011: 918471.
7. Anurathapan U, Chan RC, Hindi HF, Mucharla R, Bajgain P, Hayes BC et al. Kinetics of tumor destruction by chimeric antigen receptor-modified T cells. Mol Ther 2014; 22: 623–633.
8. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013; 368: 1509–1518.
9. Lamers CH, Sleijfer S, Vulto AG, Kruit WH, Kliffen M, Debets R et al. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol 2006; 24: e20–e22.
10. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 2010; 18: 843–851.
11. Ehninger A, Kramer M, Rollig C, Thiede C, Bornhauser M, von Bonin M et al. Distribution and levels of cell surface expression of CD33 and CD123 in acute myeloid leukemia. Blood Cancer J 2014; 4: e218.
12. Barrett AJ, Le BK. Immunotherapy prospects for acute myeloid leukaemia. Clin Exp Immunol 2010; 161: 223–232.
13. Walter RB, Appelbaum FR, Estey EH, Bernstein ID. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood 2012; 119: 6198–6208.
14. Taussig DC, Pearce DJ, Simpson C, Rohatiner AZ, Lister TA, Kelly G et al. Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. Blood 2005; 106: 4086–4092.
15. Arndt C, Feldmann A, von Bonin M, Cartellieri M, Ewen EM, Koristka S et al. Costimulation improves the killing capability of T cells redirected to tumor cells expressing low levels of CD33: description of a novel modular targeting system. Leukemia 2014; 28: 59–69.
16. Koristka S, Cartellieri M, Arndt C, Bippes CC, Feldmann A, Michalk I et al. Retargeting of regulatory T cells to surface-inducible autoantigen La/SS-B. J Autoimmun 2013; 42: 105–116.
17. Cartellieri M, Koristka S, Arndt C, Feldmann A, Stamova S, von Bonin M et al. A novel ex vivo isolation and expansion procedure for chimeric antigen receptor engrafted human T cells. PLoS One 2014; 9: e93745.
18. Bippes CC, Feldmann A, Stamova S, Cartellieri M, Schwarzer A, Wehner R et al. A novel modular antigen delivery system for immuno targeting of human 6-sulfo LacNAc-positive blood dendritic cells (SlanDCs). PLoS One 2011; 6: e16315.
19. Stirnnagel K, Luftenegger D, Stange A, Swiersy A, Mullers E, Reh J et al. Analysis of prototype foamy virus particle-host cell interaction with autofluorescent retroviral particles. Retrovirology 2010; 7: 45.
20. Szymczak AL, Workman CJ, Wang Y, Vignali KM, Dilioglou S, Vanin EF et al. Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector. Nat Biotechnol 2004; 22: 589–594.
21. Arndt C, von Bonin M, Cartellieri M, Feldmann A, Koristka S, Michalk I et al. Redirection of T cells with a first fully humanized bispecific CD33-CD3 antibody efficiently eliminates AML blasts without harming hematopoietic stem cells. Leukemia 2013; 27: 964–967.
22. Tettamanti S, Biondi A, Biagi E, Bonnet D. CD123 AML targeting by chimeric antigen receptors: a novel magic bullet for AML therapeutics? Oncoimmunology 2014; 3: e28835.
23. Feldmann A, Arndt C, Topfer K, Stamova S, Krone F, Cartellieri M et al. Novel humanized and highly efficient bispecific antibodies mediate killing of prostate stem cell antigen-expressing tumor cells by CD8+ and CD4+ T cells. J Immunol 2012; 189: 3249–3259.
24. Koristka S, Cartellieri M, Theil A, Feldmann A, Arndt C, Stamova S et al. Retargeting of human regulatory T cells by single-chain bispecific antibodies. J Immunol 2012; 188: 1551–1558.
25. Bachmann M, Chang S, Bernd A, Mayet W, Meyer zum Buschenfelde KH, Muller WE. Translocation of the nuclear autoantigen La to cell surface: assembly and disassembly with the extracellular matrix. Autoimmunity 1991; 9: 99–107.
26. von Bonin M, Wermke M, Cosgun KN, Thiede C, Bornhauser M, Wagemaker G et al. In vivo expansion of co-transplanted T cells impacts on tumor re-initiating activity of human acute myeloid leukemia in NSG mice. PLoS One 2013; 8: e60680.
27. Rowe JM, Lowenberg B. Gemtuzumab ozogamicin in acute myeloid leukemia: a remarkable saga about an active drug. Blood 2013; 121: 4838–4841.
28. Stamova S, Cartellieri M, Feldmann A, Bippes CC, Bartsch H, Wehner R et al. Simultaneous engagement of the activatory receptors NKG2D and CD3 for retargeting of effector cells to CD33-positive malignant cells. Leukemia 2011; 25: 1053–1056.
29. Dutour A, Marin V, Pizzitola I, Valsesia-Wittmann S, Lee D, Y von E et al. In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD33 acute myeloid leukemia. Adv Hematol 2012; 2012: 683065.
30. Laszlo GS, Estey EH, Walter RB. The past and future of CD33 as therapeutic target in acute myeloid leukemia. Blood Rev 2014; 28: 143–153.
31. Marin V, Pizzitola I, Agostoni V, Attianese GM, Finney H, Lawson A et al. Cytokineinduced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors. Haematologica 2010; 95: 2144–2152.
32. Gorczyca W, Sun ZY, Cronin W, Li X, Mau S, Tugulea S. Immunophenotypic pattern of myeloid populations by flow cytometry analysis. Methods Cell Biol 2011; 103: 221–266.
33. Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL et al. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 2000; 14: 1777–1784.
34. Qiu S, Jia Y, Xing H, Yu T, Yu J, Yu P et al. N-Cadherin and Tie2 positive CD34(+) CD38(-)CD123(+) leukemic stem cell populations can develop acute myeloid leukemia more effectively in NOD/SCID mice. Leuk Res 2014; 38: 632–637.
35. He SZ, Busfield S, Ritchie DS, Hertzberg MS, Durrant S, Lewis ID et al. A Phase 1 study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia. Leuk Lymphoma 2015; 56: 1406–1415.
36. Gill S, Tasian SK, Ruella M, Shestova O, Li Y, Porter DL et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood 2014; 123: 2343–2354.
37. Mardiros A, Dos SC, McDonald T, Brown CE, Wang X, Budde LE et al. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood 2013; 122: 3138–3148.
38. Wang QS, Wang Y, Lv HY, Han QW, Fan H, Guo B et al. Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia. Mol Ther 2015; 23: 184–191.
39. Finney HM, Akbar AN, Lawson AD. Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J Immunol 2004; 172: 104–113.
40. Hombach A, Sent D, Schneider C, Heuser C, Koch D, Pohl C et al. T-cell activation by recombinant receptors: CD28 costimulation is required for interleukin 2 secretion and receptor-mediated T-cell proliferation but does not affect receptor-mediated target cell lysis. Cancer Res 2001; 61: 1976–1982.
41. Maher J, Brentjens RJ, Gunset G, Riviere I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol 2002; 20: 70–75.
42. Balkhi MY, Ma Q, Ahmad S, Junghans RP. T cell exhaustion and Interleukin 2 downregulation. Cytokine 2015; 71: 339–347.
43. Savoldo B, Ramos CA, Liu E, Mims MP, Keating MJ, Carrum G et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 2011; 121: 1822–1826.
44. Scholler J, Brady TL, Binder-Scholl G, Hwang WT, Plesa G, Hege KM et al. Decadelong safety and function of retroviral-modified chimeric antigen receptor T cells. Sci Transl Med 2012; 4: 132ra53.
45. Semsei I, Tröster H, Bartsch H, Schwemmle M, Igloi GL, Bachmann M. Isolation of rat cDNA clones coding for the autoantigen SS-B/La: detection of species-specific variations. Gene 1993; 126: 265–268.
46. Yiannaki EE, Tzioufas AG, Bachmann M, Hantoumi J, Tsikaris V, Sakarellos Daitsiotis M et al. The value of synthetic linear epitope analogues of La/SSB for the detection of autoantibodies to La/SSB; specificity, sensitivity and comparison of methods. Clin Exp Immunol 1998; 112: 152–158.