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Engineered T cell therapies

Published online by Cambridge University Press:  04 November 2015

Anne-Christine Field  and
Waseem Qasim
Anne-Christine Field*
Affiliation:
Molecular Immunology Unit, Institute of Child Health (ICH), University College London (UCL), 30 Guilford Street, London WC1N 1EH, UK
Waseem Qasim
Affiliation:
Molecular Immunology Unit, Institute of Child Health (ICH), University College London (UCL), 30 Guilford Street, London WC1N 1EH, UK
*
*Corresponding author: Anne-Christine Field, Molecular immunology Unit, Institute of Child Health (ICH), University College London (UCL), 30 Guilford Street, London WC1N 1EH, UK. E-mail: [email protected]
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Abstract

Alongside advancements in gene therapy for inherited immune disorders, the need for effective alternative therapeutic options for other conditions has resulted in an expansion in the field of research for T cell gene therapy. T cells are easily obtained and can be induced to divide robustly ex vivo, a characteristic that allows them to be highly permissible to viral vector-mediated introduction of transgenes. Pioneering clinical trials targeting cancers and infectious diseases have provided safety and feasibility data and important information about persistence of engineered cells in vivo. Here, we review clinical experiences with γ-retroviral and lentiviral vectors and consider the potential of integrating transposon-based vectors as well as specific genome editing with designer nucleases in engineered T cell therapies.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 17 , 2015 , e19
Copyright
Copyright © Cambridge University Press 2015 

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References

1. Ginn, S.L. et al. (2013) Gene therapy clinical trials worldwide to 2012 – an update. Journal of Gene Medicine 15, 65–77 Google Scholar
2. Rosenberg, S.A. et al. (1990) Gene transfer into humans–immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. New England Journal of Medicine 323, 570–578 Google Scholar
3. Blaese, R.M. et al. (1995) T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years. Science 270, 475–480 Google Scholar
4. Bordignon, C. et al. (1995) Gene therapy in peripheral blood lymphocytes and bone marrow for ADA- immunodeficient patients. Science 270, 470–475 Google Scholar
5. Muul, L.M. et al. (2003) Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial. Blood 101, 2563–2569 Google Scholar
6. Riddell, S.R. et al. (1996) T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nature Medicine 2, 216–223 CrossRefGoogle ScholarPubMed
7. Bonini, C. et al. (1997) HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276, 1719–1724 Google Scholar
8. Burt, R.K. et al. (2003) Herpes simplex thymidine kinase gene-transduced donor lymphocyte infusions. Experimental Hematology 31, 903–910 Google Scholar
9. Tiberghien, P. et al. (2001) Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft. Blood 97, 63–72 CrossRefGoogle ScholarPubMed
10. Fehse, B. et al. (2004) Evidence for increased risk of secondary graft failure after in vivo depletion of suicide gene-modified T lymphocytes transplanted in conjunction with CD34+ enriched blood stem cells. Blood 104, 3408–3409 Google Scholar
11. Ciceri, F. et al. (2009) Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncology 10, 489–500 Google Scholar
12. Vago, L. et al. (2012) T-cell suicide gene therapy prompts thymic renewal in adults after hematopoietic stem cell transplantation. Blood 120, 1820–1830 Google Scholar
13. Borchers, S. et al. (2011) Genetically modified donor leukocyte transfusion and graft-versus-leukemia effect after allogeneic stem cell transplantation. Human Gene Therapy 22, 829–841 Google Scholar
14. Zhan, H. et al. (2013) Production and first-in-man use of T cells engineered to express a HSVTK-CD34 sort-suicide gene. PLoS ONE 8, e77106 Google Scholar
15. Di Stasi, A. et al. (2011) Inducible apoptosis as a safety switch for adoptive cell therapy. New England Journal of Medicine 365, 1673–1683 Google Scholar
16. Morgan, R.A. et al. (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314, 126–129 CrossRefGoogle ScholarPubMed
17. Burns, W.R. et al. (2009) Lack of specific gamma-retroviral vector long terminal repeat promoter silencing in patients receiving genetically engineered lymphocytes and activation upon lymphocyte restimulation. Blood 114, 2888–2899 Google Scholar
18. Johnson, L.A. et al. (2009) Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114, 535–546 Google Scholar
19. Robbins, P.F. et al. (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. Journal of Clinical Oncology 29, 917–924 CrossRefGoogle ScholarPubMed
20. Morgan, R.A. et al. (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. Journal of Immunotherapy 36, 133–151 Google Scholar
21. Qasim, W. et al. (2013) Production and use of autologous gene modified T cells targeting metastatic hepatitis B associated hepatocellular carcinoma. Human Gene Therapy A25–A26 Google Scholar
22. Sadelain, M., Brentjens, R. and Riviere, I. (2013) The basic principles of chimeric antigen receptor design. Cancer Discovery 3, 388–398 Google Scholar
23. Lamers, C.H. et al. (2006) Process validation and clinical evaluation of a protocol to generate gene-modified T lymphocytes for imunogene therapy for metastatic renal cell carcinoma: GMP-controlled transduction and expansion of patient's T lymphocytes using a carboxy anhydrase IX-specific scFv transgene. Cytotherapy 8, 542–553 Google Scholar
24. Kershaw, M.H. et al. (2006) A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clinical Cancer Research 12, 6106–6115 Google Scholar
25. Pule, M.A. et al. (2008) Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nature Medicine 14, 1264–1270 Google Scholar
26. Louis, C.U. et al. (2011) Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 118, 6050–6056 CrossRefGoogle ScholarPubMed
27. Savoldo, B. et al. (2011) CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. Journal of Clinical Investigation 121, 1822–1826 Google Scholar
28. Kochenderfer, J.N. 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, 4099–4102 CrossRefGoogle Scholar
29. Kochenderfer, J.N. 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 Google Scholar
30. Brentjens, R.J. 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, 4817–4828 Google Scholar
31. Brentjens, R.J. et al. (2013) CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Science Translational Medicine 5, 177ra38 Google Scholar
32. Davila, M.L. et al. (2014) Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science Translational Medicine 6, 224ra25 Google Scholar
33. Kochenderfer, J.N. et al. (2013) Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 122, 4129–4139 Google Scholar
34. Cruz, C.R. et al. (2013) Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood 122, 2965–2973 Google Scholar
35. Morgan, R.A. et al. (2010) Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Molecular Therapy 18, 843–851 Google Scholar
36. Ranga, U. et al. (1998) Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals. Proceedings of the National Academy of Sciences of the United States of America 95, 1201–1206 Google Scholar
37. Wong-Staal, F., Poeschla, E.M. and Looney, D.J. (1998) A controlled, Phase 1 clinical trial to evaluate the safety and effects in HIV-1 infected humans of autologous lymphocytes transduced with a ribozyme that cleaves HIV-1 RNA. Human Gene Therapy 9, 2407–2425 Google Scholar
38. Deeks, S.G. et al. (2002) A phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy. Molecular Therapy 5, 788–797 Google Scholar
39. Mitsuyasu, R.T. et al. (2000) Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency virus-infected subjects. Blood 96, 785–793 Google Scholar
40. Macpherson, J.L. et al. (2005) Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients. Journal of Gene Medicine 7, 552–564 Google Scholar
41. Morgan, R.A. et al. (2005) Preferential survival of CD4+ T lymphocytes engineered with anti-human immunodeficiency virus (HIV) genes in HIV-infected individuals. Human Gene Therapy 16, 1065–1074 Google Scholar
42. van Lunzen, J. et al. (2007) Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus. Molecular Therapy 15, 1024–1033 Google Scholar
43. Hoxie, J.A. and June, C.H. (2012) Novel cell and gene therapies. Cold Spring Harbor Perspectives in Medicine 2(10). pii: a007179. doi: 10.1101/cshperspect.a007179.Google Scholar
44. Wu, X. et al. (2003) Transcription start regions in the human genome are favored targets for MLV integration. Science 300, 1749–1751 CrossRefGoogle ScholarPubMed
45. Hacein-Bey-Abina, S. et al. (2003) LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302, 415–419 Google Scholar
46. Hacein-Bey-Abina, S. et al. (2008) Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. Journal of Clinical Investigation 118, 3132–3142 Google Scholar
47. Ott, M.G. et al. (2006) Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nature Medicine 12, 401–409 Google Scholar
48. Boztug, K. et al. (2010) Stem-cell gene therapy for the Wiskott-Aldrich syndrome. New England Journal of Medicine 363, 1918–1927 Google Scholar
49. Braun, C.J. et al. (2014) Gene therapy for wiskott-Aldrich syndrome–long-term efficacy and genotoxicity. Science Translational Medicine 6, 227ra33 Google Scholar
50. Newrzela, S. et al. (2008) Resistance of mature T cells to oncogene transformation. Blood 112, 2278–2286 Google Scholar
51. Newrzela, S. et al. (2011) Retroviral insertional mutagenesis can contribute to immortalization of mature T lymphocytes. Molecular Medicine 17, 1223–1232 Google Scholar
52. Heinrich, T. et al. (2013) Mature T-cell lymphomagenesis induced by retroviral insertional activation of Janus kinase 1. Molecular Therapy 21, 1160–1168 CrossRefGoogle ScholarPubMed
53. Recchia, A. et al. (2006) Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells. Proceedings of the National Academy of Sciences of the United States of America 103, 1457–1462 Google Scholar
54. Bukrinsky, M. (2004) A hard way to the nucleus. Molecular Medicine 10, 1–5 Google Scholar
55. Bukrinsky, M.I. et al. (1993) A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365, 666–669 Google Scholar
56. Naldini, L. et al. (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272, 263–267 Google Scholar
57. Miyoshi, H. et al. (1998) Development of a self-inactivating lentivirus vector. Journal of Virology 72, 8150–8157 Google Scholar
58. Zufferey, R. et al. (1998) Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. Journal of Virology 72, 9873–9880 Google Scholar
59. Sakuma, T., Barry, M.A. and Ikeda, Y. (2012) Lentiviral vectors: basic to translational. Biochemical Journal 443, 603–618 Google Scholar
60. Dupuy, F.P. et al. (2005) Lentiviral transduction of human hematopoietic cells by HIV-1- and SIV-based vectors containing a bicistronic cassette driven by various internal promoters. Journal of Gene Medicine 7, 1158–1171 CrossRefGoogle ScholarPubMed
61. Zufferey, R. et al. (1999) Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. Journal of Virology 73, 2886–2892 CrossRefGoogle ScholarPubMed
62. Osti, D. et al. (2006) Comparative analysis of molecular strategies attenuating positional effects in lentiviral vectors carrying multiple genes. Journal of Virological Methods 136, 93–101 Google Scholar
63. Zhang, F. et al. (2007) Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells. Blood 110, 1448–1457 Google Scholar
64. Funke, S. et al. (2008) Targeted cell entry of lentiviral vectors. Molecular Therapy 16, 1427–1436 Google Scholar
65. Dropulic, B. (2011) Lentiviral vectors: their molecular design, safety, and use in laboratory and preclinical research. Human Gene Therapy 22, 649–657 Google Scholar
66. Relander, T. et al. (2005) Gene transfer to repopulating human CD34+ cells using amphotropic-, GALV-, or RD114-pseudotyped HIV-1-based vectors from stable producer cells. Molecular Therapy 11, 452–459 Google Scholar
67. Kutner, R.H., Zhang, X.Y. and Reiser, J. (2009) Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors. Nature Protocols 4, 495–505 Google Scholar
68. Baekelandt, V. et al. (2003) Optimized lentiviral vector production and purification procedure prevents immune response after transduction of mouse brain. Gene Therapy 10, 1933–1940 Google Scholar
69. Tuschong, L. et al. (2002) Immune response to fetal calf serum by two adenosine deaminase-deficient patients after T cell gene therapy. Human Gene Therapy 13, 1605–1610 Google Scholar
70. Levine, B.L. et al. (2006) Gene transfer in humans using a conditionally replicating lentiviral vector. Proceedings of the National Academy of Sciences of the United States of America 103, 17372–17377 Google Scholar
71. Cartier, N. et al. (2009) Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326, 818–823 Google Scholar
72. Cavazzana-Calvo, M. et al. (2010) Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 467, 318–322 CrossRefGoogle ScholarPubMed
73. Porter, D.L. et al. (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. New England Journal of Medicine 365, 725–733 Google Scholar
74. Aiuti, A. et al. (2013) Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 341, 1233151 Google Scholar
75. Biffi, A. et al. (2013) Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341, 1233158 Google Scholar
76. Wang, G.P. et al. (2009) Analysis of lentiviral vector integration in HIV+ study subjects receiving autologous infusions of gene modified CD4+ T cells. Molecular Therapy 17, 844–850 Google Scholar
77. Grupp, S.A. et al. (2013) Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. New England Journal of Medicine 368, 1509–1518 Google Scholar
78. Kalos, M. et al. (2011) T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Science Translational Medicine 3, 95ra73 Google Scholar
79. Linette, G.P. et al. (2013) Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122, 863–871 Google Scholar
80. Cameron, B.J. et al. (2013) Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Science Translational Medicine 5, 197ra103 Google Scholar
81. Hildinger, M. et al. (2001) Membrane-anchored peptide inhibits human immunodeficiency virus entry. Journal of Virology 75, 3038–3042 Google Scholar
82. Burke, B.P. et al. (2014) CCR5 as a natural and modulated target for inhibition of HIV. Viruses 6, 54–68 Google Scholar
83. Flemming, A. (2014) Deal watch: Pfizer and GSK join race for T cell cancer therapies. Nature Review Drug Discovery 13, 568–569 Google Scholar
84. Ivics, Z. et al. (1997) Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91, 501–510 Google Scholar
85. Kawakami, K. (2007) Tol2: a versatile gene transfer vector in vertebrates. Genome Biology 8(Suppl 1), S7 Google Scholar
86. Ding, S. et al. (2005) Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice. Cell 122, 473–483 Google Scholar
87. Hackett, P.B., Largaespada, D.A. and Cooper, L.J. (2010) A transposon and transposase system for human application. Molecular Therapy 18, 674–683 Google Scholar
88. Yant, S.R. et al. (2004) Mutational analysis of the N-terminal DNA-binding domain of sleeping beauty transposase: critical residues for DNA binding and hyperactivity in mammalian cells. Molecular and Cellular Biology 24, 9239–9247 Google Scholar
89. Mates, L. et al. (2009) Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates. Nature Genetics 41, 753–761 Google Scholar
90. Huang, X. et al. (2006) Stable gene transfer and expression in human primary T cells by the Sleeping Beauty transposon system. Blood 107, 483–491 Google Scholar
91. Peng, P.D. et al. (2009) Efficient nonviral Sleeping Beauty transposon-based TCR gene transfer to peripheral blood lymphocytes confers antigen-specific antitumor reactivity. Gene Therapy 16, 1042–1049 Google Scholar
92. Field, A.C. et al. (2013) Comparison of lentiviral and sleeping beauty mediated alphabeta T cell receptor gene transfer. PLoS ONE 8, e68201 Google Scholar
93. Kebriaei, P. et al. (2012) Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies. Human Gene Therapy 23, 444–450 Google Scholar
94. Singh, H. et al. (2014) A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19. Immunological Reviews 257, 181–190 Google Scholar
95. Perez, E.E. et al. (2008) Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nature Biotechnology 26, 808–816 Google Scholar
96. Maier, D.A. et al. (2013) Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5. Human Gene Therapy 24, 245–258 CrossRefGoogle ScholarPubMed
97. Tebas, P. et al. (2014) Gene editing of CCR5 in autologous CD4T cells of persons infected with HIV. New England Journal of Medicine 370, 901–910 Google Scholar
98. Torikai, H. et al. (2012) A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood 119, 5697–5705 Google Scholar
99. Provasi, E. et al. (2012) Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nature Medicine 18, 807–815 Google Scholar
100. Berdien, B. et al. (2014) TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer. Gene Therapy 21, 539–548 Google Scholar
101. Koh, S. et al. (2013) A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Molecular Therapy–Nucleic Acids 2, e114 Google Scholar
102. Mali, P., Esvelt, K.M. and Church, G.M. (2013) Cas9 as a versatile tool for engineering biology. Nature Methods 10, 957–963 Google Scholar
103. Meissner, T.B. et al. (2014) Genome editing for human gene therapy. Methods in Enzymology 546, 273–295 Google Scholar