Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: Current strategies and recent advances

Therapeutic Advances in Hematology

Volumn 6, Issue 6, 2015, Pages 295-307

  Mclaughlin, Lauren ^a   Cruz, C Russell ^a   Bollard, Catherine M ^a  

^a GEORGE WASHINGTON UNIVERSITY   (United States)

Author keywords

antigen specific T cells; chimeric antigen receptor; cytotoxic T lymphocytes; immunotherapy

Indexed keywords

EID: 84993682626     PISSN: 20406207     EISSN: 20406215     Source Type: Journal    
DOI: 10.1177/2040620715594736     Document Type: Review

References (89)

1. Ansell S. (2014) Brentuximab vedotin. Blood 124: 3197–3200.
2. Bargou R. Leo E. Zugmaier G. Klinger M. Goebeler M. Knop S. et al. (2008) Tumor regression in cancer patients by very low doses of T cell-engaging antibody. Science 321: 974–977.
3. Bendle G. Linnemann C. Hooijkaas A. Bies L. de Witte M. Jorritsma A. et al. (2010) Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med 16: 565–570.
4. Bleakley M. Riddell S. (2011) Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia. Immunol Cell Biol 89: 396–407.
5. Bollard C. Gottschalk S. Torrando V. Diouf O. Ku S. Hazrat Y. et al. (2014) Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol 32: 798–808.
6. Bollard C. Kuehnle I. Leen A. Rooney C. Heslop H. (2004) Adoptive immunotherapy for posttransplantation viral infections. Biol Blood Marrow Transplant 10: 143–155.
7. Bollard C. Rossig C. Calonge M. Huls M. Wagner H. Massague J. et al. (2002) Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood 99: 3179–3187.
8. Bornhauser M. Thiede C. Babatz J. Schetelig J. Illmer T. Kiani A. et al. (2006) Infusion of bcr.abl peptide-reactive donor T cells to achieve molecular remission of chronic myeloid leukemia after CD34+ selected allogeneic hematopoietic cell transplantation. Leukemia 11: 2055–2057.
9. Bornhauser M. Thiede C. Platzbecker U. Kiana A. Oelschlaegel U. Babatz J. et al. (2011) Prophylactic transfer of BCR-ABL-, PR1-, and WT1-reactive donor T-cells after T cell-depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia. Blood 117: 7174–7184.
10. Brentjens R. Curran K. (2012) Novel cellular therapies for leukemia: CAR-modified T cells targeted to the CD19 antigen. Hematology Am Soc Hematol Educ Program 2012: 143–151.
11. Brentjens R. Davila M. Riviere I. Park J. Wang X. Cowell L. et al. (2013) CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 5: 177ra38.
12. Brieger J. Weidmann E. Fenchel K. Mitrou P. Hoelzer D. Bergmann L. (1994) The expression of the Wilms’ tumor gene in acute myelocytic leukemias as a possible marker for leukemic blast cells. Leukemia 8: 2138–2143.
13. Bross P. Beitz J. Chen G. Chen X. Duffy E. Kieffer L. et al. (2001) Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res 7: 1490–1496.
14. Budde L. Berger C. Lin Y. Wang J. Lin X. Frayo S. et al. (2013) Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide switch to improve the efficacy and safety of T cell adoptive immunotherapy for lymphoma. PloS ONE 8: e82742.
15. Cameron B. Gerry A. Duke J. Harper J. Kannan V. Bianchi F. et al. (2013) Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. Sci Transl Med 5: 197-203.
16. Chapuis A. Ragnarsson G. Nguyen H. Chaney C. Pufnock J. Schmitt T. et al. (2013) Transferred WT1-reactive CD8+ T cells can mediate antileukemic activity and persist in post-transplant patients. Sci Transl Med 5: 174-227.
17. Creutzig U. Harbott J. Sperling C. Ritter J. Zimmermann M. Loffler H. et al. (1995) Clinical significance of surface antigen expression in children with acute myeloid leukemia results of study AML-BFM-87. Blood 86: 3097–3108.
18. Cruz C. Gerdemann U. Leen A. Shaffer J. Ku S. Tzou B. et al. (2011) Improving T-cell therapy for relapsed EBV-negative Hodgkin lymphoma by targeting upregulated MAGE-A4. Clin Cancer Res 17: 7058–7066.
19. Cruz C. Micklethwaite K. Savoldo B. Ramos C. Lam S. Ku S. 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.
20. Curran K. Pegram H. Brentjens R. (2012) Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions. J Gene Med 14: 405–415.
21. Deol A. Lum L. (2010) Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treat Rev 36: 528–538.
22. Dinndorf P. Andrews R. Benjamin D. Ridgway D. Bernstein I. (1986) Expression of normal myeloid-associated antigens by acute leukemia cells. Blood 67: 1048–1053.
23. Di Stasi A. Tey S. Dotti G. Fujita Y. Kennedy-Nasser A. Martinez C. et al. (2011) Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med 365: 1673–1683.
24. Distler E. Bloetz A. Albrecht J. Asdufan S. Hohberger A. Frey M. et al. (2011) Alloreactive and leukemia-reactive T-cells are preferentially derived from naive precursors in healthy donors: implications for immunotherapy with memory T cells. Haematologica 96: 1024–1032.
25. Falkenburg J. Wafelman A. Joosten P. Smit W. van Bergen C. Bongaerts R. et al. (1999) Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes. Blood 94: 1201–1208.
26. Finney H. Lawson A. Bebbington C. Weir A. (1998) Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol 161: 2791–2797.
27. Foster A. Dotti G. Lu A. Khalil M. Brenner M. Heslop H. et al. (2008) Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor. J Immunother 31: 500–505.
28. Gerdemann U. Katari U. Christin A. Cruz C. Tripic T. Rousseau A. et al. (2011) Cytotoxic T lymphocytes simultaneously targeting multiple tumor-associated antigens to treat EBV negative lymphoma. Mol Ther 19: 2258–2268.
29. Goodyear O. Agathanggelou A. Novitzky-Basso I. Siddique S. Mcskeane T. Ryan G. et al. (2010) Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood 116: 1908–1918.
30. Grada Z. Hegde M. Byrd T. Shaffer D. Ghazi A. Brawley V. et al. (2013) TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids 2: e105.
31. Grillo-Lopez A. White C. Dallaire B. Varns C. Shen C. Wei A. et al. (2000) Rituximab: the first monoclonal antibody approved for the treatment of lymphoma. Curr Pharm Biotechnol 1: 1–9.
32. Gross G. Waks T. Eshhar Z. (1989) Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci USA 86: 10024–10028.
33. Grupp S. Kalos M. Barrett D. Aplenc R. Porter D. Rheingold S. et al. (2013) Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368: 1509–1518.
34. Haque T. Mcaulay K. Kelly D. Crawford D. (2010) Allogeneic T-cell therapy for Epstein-Barr virus-positive posttransplant lymphoproliferative disease: long-term follow-up. Transplantation 90: 93–94.
35. Haso W. Lee D. Shah N. Stetler-Stevenson M. Yuan C. Pastan I. et al. (2013) Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood 121: 1165–1174.
36. Heslop H. Slobod K. Pule M. Hale G. Rousseau A. Smith C. et al. (2010) Long-term outcome of EBV-specific T cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood 115: 925–935.
37. Hinrichs C. Borman Z. Gattinoni L. Yu Z. Burns W. Huang J. et al. (2011) Human effector CD8+ T-cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood 117: 808–814.
38. Hinrichs C. Spolski R. Paulos C. Gattinoni L. Kerstann K. Palmer D. et al. (2008) IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood 111: 5326–5333.
39. Hoyos V. Savoldo B. Quintarelli C. Mahendravada A. Zhang M. Hoyos V. et al. (2010) Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 24: 1160–1170.
40. Janeway C. Travers P. Walport M. Schlomchik J. (2005) Immunobiology: The Immune System in Health and Disease. New York and London: Garland Science Publishing.
41. Jena B. Dotti G. Cooper L. (2010) Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood 116: 1035–1044.
42. Jensen M. Popplewell L. Cooper L. Digiusto D. Kalos M. Osteberg J. et al. (2010) Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T-cells in humans. Biol Blood Marrow Transplant 16: 1245–1256.
43. Johnson L. Morgan R. Dudley M. Cassard L. Yang J. Hughes M. 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.
44. Jonnalagadda M. Mardiros A. Urak R. Wang X. Hoffman L. Bernanke A. et al. (2014) Chimeric antigen receptors with mutated IgG 4 Fc spacer avoid fc receptor binding and improve T cell persistence and antitumor efficacy. Mol Ther 23: 757–768.
45. Kalos M. Levine B. Porter D. Katz S. Grupp S. Bagg A. 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: 95ra73.
46. Kochenderfer J. Dudley M. Feldman S. Wilson W. Spaner D. Maric I. 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.
47. Kochenderfer J. Dudley M. Kassim S. Somerville R. Carpenter R. Stetler-Stevenson M. 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: 540–549.
48. Kochenderfer J. Wilson W. Janik J. Dudley M. Stetler-Stevenson M. Feldman S. 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.
49. Kolb H. Mittermuller J. Clemm C. Holler E. Ledderose G. Brehm G. et al. (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76: 2462–2465.
50. Kowolik C. Topp M. Gonzalez S. Pfeiffer T. Olivares S. Gonzalez N. 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.
51. Lee D. Gardner R. Porter D. Louise C. Ahmed N. Jensen M. et al. (2014) Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124: 188–195.
52. Lee D. Kochenderfer J. Stetler-Stevenson M. Cui Y. Delbrook C. Feldman S. 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: 517–528.
53. Li Y. Bleakley M. Yee C. (2005) IL-21 influences the frequency, phenotype, and affinity of the antigen-specific CD8 T cell response. J Immunol 175: 2261–2269.
54. Liddy N. Bossi G. Adams K. Lissina A. Mahon T. Hassan N. et al. (2012) Monoclonal TCR-redirected tumor cell killing. Nat Med 18: 980–988.
55. Linette G. Stadtmauer E. Maus M. Rapoport A. Levine B. Emery L. et al. (2013) Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122: 863–871.
56. Maher J. Brentjens R. Gunset G. Riviere I. Sadelain M. (2002) Human T-lymphocytes cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol 20: 70–75.
57. Mardiros A. Dos Santos C. McDonald T. Brown C. Wang X. Buddge L. 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: 3138–3148.
58. Menssen H. Renkl H. Rodeck U. Maurer J. Notter M. Schwartz S. et al. (1995) Presence of Wilms’ tumor gene (WT1) transcripts and the WT 1 nuclear protein in the majority of human acute leukemias. Leukemia 9: 1060–1067.
59. Micklethwaite K. Savoldo B. Hanley P. Leen A. Demmler-Harrison G. Cooper L. et al. (2010) Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation. Blood 115: 2695–2703.
60. Morgan R. Dudley M. Wunderlich J. Hughes M. Yang J. Sherry R. et al. (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314: 126–129.
61. Morgan R. Chinnasamy N. Abate-Daga D. Gros A. Robbins P. Zheng Z. et al. (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36: 133–151.
62. Nikiforow S. Alyea E. (2014) Maximizing GVL in allogeneic transplantation: role of donor lymphocyte infusions. Hematology Am Soc Hematol Educ Program 1: 570–575.
63. O'Reilly R. Lacerda J. Lucas K. Rosenfield N. Small T. Papadopoulos E. (1996) Adoptive cell therapy with donor lymphocytes for EBV-associated lymphomas developing after allogeneic marrow transplants. Important Adv Oncol 149–166.
64. Pardoll D. (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12: 252–264.
65. Petersdorf S. Kopecky K. Slovak M. Willman C. Nevill T. Brandwein J. et al. (2013) A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood 121: 4854–4860.
66. Porter D. Levine B. Kalos M. Bagg A. June C. (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365: 725–733.
67. Rezvani K. Yong A. Savani B. Mielke S. Keyvanfar K. Gostick E. et al. (2007) Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia. Blood 110: 1924–1932.
68. Ritchie D. Neeson P. Khot A. Peinert S. Tai T. Tainton K. et al. (2013) Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 21: 2122–2129.
69. Rosenberg S. (2010) Of mice, not men: no evidence for graft-versus-host disease in humans receiving T-cell receptor-transduced autologous T-cells. Mol Ther 18: 1744–1745.
70. Rosenberg S. (2011) Cell transfer immunotherapy for metastatic solid cancer–what clinicians need to know. Nat Rev Clin Oncol 8: 577–585.
71. Rossig C. Bollard C. Nuchtern J. Rooney C. Brenner M. (2002) Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy. Blood 99: 2009–2016.
72. Savoldo B. Ramos C. Liu E. Mims M. Keating M. Carrum G. et al. (2011) CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 121: 1822–1826.
73. Schumacher T. (2002) T-cell-receptor gene therapy. Nat Rev Immunol 2: 512–519.
74. Singh H. Figliola M. Dawson M. Huls H. Olivares S. Switzer K. et al. (2011) Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lineage malignancies. Cancer Res 71: 3516–3527.
75. Terakura S. Yamamoto T. Gardner R. Turtle C. Jensen M. Riddell S. (2012) Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells. Blood 119: 72–82.
76. Till B. Jensen M. Wang J. Chen E. Wood B. Greisman H. et al. (2008) Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 112: 2261–2271.
77. Till B. Jensen M. Wang J. Qian X. Gopal A. Maloney D. 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: 3940–3950.
78. Topalian S. Drake C. Pardoll D. (2015) Immune checkpoint blockage: a common denominator approach to cancer therapy. Cancer Cell 27: 450–461.
79. Topp M. Gokbuget N. Zugmaier G. Degenhard E. Goebeler M. Klinger M. et al. (2012) Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 120: 5185–5187.
80. Vera J. Brenner L. Gerdemann U. Ngo M. Sili U. Liu H. et al. (2010) Accelerated production of antigen-specific T cells for preclinical and clinical applications using gas-permeable rapid expansion cultureware (G-Rex). J Immunother 33: 305–315.
81. von Stackelberg A. Zugmaier G. Handgretinger R. Locatelli F. Rizzari C. Trippett T. et al. (2013) A phase 1 / 2 study of blinatumomab in pediatric patients with relapsed / refractory B-cell precursor acute lymphoblastic leukemia. Blood 122: 70.
82. Vickers M. Wilkie G. Robinson N. Rivera N. Haque T. Crawford D. et al. (2014) Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease. Br J Haematol 167: 402–410.
83. Wang X. Naranjo A. Brown C. Bautista C. Wong C. Chang W. et al. (2012) Phenotypic and functional attributes of lentivirus-modified CD19-specific human CD8+ central memory T cells manufactured at clinical scale. J Immunother 35: 689–701.
84. Wang Q. Wang Y. Lv H. Han Q. Fan H. Guo B. 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: 184–191.
85. Warren E. Fujii N. Akatsuka Y. Chaney C. Mito J. Loeb K. et al. (2010) Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens. Blood 115: 3869–3878.
86. Weber G. Caruana I. Rouce R. Barrett A. Gerdemann U. Leen A. et al. (2013 a) Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia–implications for immunotherapy. Clin Cancer Res 19: 5079–5091.
87. Weber G. Gerdemann U. Caruana I. Savoldo B. Hensel N. Rabin K. et al. (2013 b) Generation of multi-leukemia antigen-specific T cells to enhance the graft-versus-leukemia effect after allogeneic stem cell transplant. Leukemia 27: 1538–1547.
88. Younes A. Bartlett N. Leonard J. Kennedy D. Lynch C. Sievers E. et al. (2010) Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363: 1812–1821.
89. Zhou X. Di Stasi A. Tey S. Krance R. Martinez C. Leung K. et al. (2014) Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene. Blood 123: 3895–3905.