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

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 chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013; 5: 177ra38.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Barrett AJ, Le BK . Immunotherapy prospects for acute myeloid leukaemia. Clin Exp Immunol 2010; 161: 223–232.

Walter RB, Appelbaum FR, Estey EH, Bernstein ID . Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood 2012; 119: 6198–6208.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Rowe JM, Lowenberg B . Gemtuzumab ozogamicin in acute myeloid leukemia: a remarkable saga about an active drug. Blood 2013; 121: 4838–4841.

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.

Dutour A, Marin V, Pizzitola I, Valsesia-Wittmann S, Lee D, Yvon 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.

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.

Marin V, Pizzitola I, Agostoni V, Attianese GM, Finney H, Lawson A et al. Cytokine-induced 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Balkhi MY, Ma Q, Ahmad S, Junghans RP . T cell exhaustion and Interleukin 2 downregulation. Cytokine 2015; 71: 339–347.

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.

Scholler J, Brady TL, Binder-Scholl G, Hwang WT, Plesa G, Hege KM et al. Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci Transl Med 2012; 4, 132ra53.

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.

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.