Genetically modified T cells to target glioblastoma

Frontiers in Oncology

Volumn 3 DEC, Issue , 2013, Pages

  Krebs, Simone ^a,b   Rodríguez Cruz, Tania G ^a,b   DeRenzo, Christopher ^a,b   Gottschalk, Stephen ^a,b  

^a CENTER FOR CELL AND GENE THERAPY   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Genetically modified T cells; Glioblastoma; Immunotherapy; T cell therapy

Indexed keywords

ACICLOVIR; CARCINOEMBRYONIC ANTIGEN; CD134 ANTIGEN; CD137 ANTIGEN; CD19 ANTIGEN; CD27 ANTIGEN; CD28 ANTIGEN; CHEMOKINE RECEPTOR; CHONDROITIN SULFATE; DENDRITIC CELL VACCINE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPSTEIN BARR VIRUS ANTIGEN 2; GANCICLOVIR; GLYCOPROTEIN GP 100; INFLIXIMAB; MELAN A; MELANOMA ANTIGEN 3; MONOCLONAL ANTIBODY; NY ESO 1 ANTIGEN; RITUXIMAB; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; STEROID; T LYMPHOCYTE RECEPTOR; TEMOZOLOMIDE; TOCILIZUMAB; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA2; UNINDEXED DRUG; VALACICLOVIR; VASCULOTROPIN;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CELL THERAPY; CYTOKINE PRODUCTION; DISULFIDE BOND; DNA MODIFICATION; GENE SILENCING; GENE TRANSFER; GLIOBLASTOMA; HUMAN; IMMUNE RESPONSE; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTHERAPY; MAJOR HISTOCOMPATIBILITY COMPLEX; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; UNSPECIFIED SIDE EFFECT;

EID: 84892421576     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2013.00322     Document Type: Review

References (113)

1. Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA (2013) 310:1842-50. doi: 10.1001/jama.2013.280319.
2. DeAngelis LM. Brain tumors. N Engl J Med (2001) 344:114-23. doi:10.1056/NEJM200101113440207.
3. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol (2009) 10:459-66. doi:10.1016/S1470-2045(09)70025-7.
4. Tanaka S, Louis DN, Curry WT, Batchelor TT, Dietrich J. Diagnostic and therapeutic avenues for glioblastoma: no longer a dead end? Nat Rev Clin Oncol (2013) 10:14-26. doi:10.1038/nrclinonc.2012.204.
5. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature (2006) 444:756-60. doi:10.1038/nature05236.
6. Frosina G. DNA repair and resistance of gliomas to chemotherapy and radiotherapy. Mol Cancer Res (2009) 7:989-99. doi:10.1158/1541-7786.MCR-09-0030.
7. Albesiano E, Han JE, Lim M. Mechanisms of local immunoresistance in glioma. Neurosurg Clin N Am (2010) 21:17-29. doi:10.1016/j.nec.2009.08.008.
8. Johnson LA, Sampson JH. Immunotherapy approaches for malignant glioma from 2007 to 2009. Curr Neurol Neurosci Rep (2010) 10:259-66. doi:10.1007/s11910-010-0111-9.
9. Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol (2011) 29:330-6. doi:10.1200/JCO.2010.30.7744.
10. Sampson JH, Heimberger AB, Archer GE, Aldape KD, Friedman AH, Friedman HS, et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol (2010) 28:4722-9. doi:10.1200/JCO.2010.28.6963.
11. Wheeler CJ, Black KL. DCVax-brain and DC vaccines in the treatment of GBM. Expert Opin Investig Drugs (2009) 18:509-19. doi:10.1517/13543780902841951.
12. Brenner MK, Heslop HE. Adoptive T cell therapy of cancer. Curr Opin Immunol (2010) 22:251-7. doi:10.1016/j.coi.2010.01.020.
13. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol (2012) 12:269-81. doi:10.1038/nri3191.
14. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood (2009) 114:535-46. doi:10.1182/blood-2009-03-211714.
15. Pule MA, Savoldo B, Myers GD, Rossig C, Russell HV, Dotti G, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med (2008) 14:1264-70. doi:10.1038/nm.1882.
16. Louis CU, Savoldo B, Dotti G, Pule M, Yvon E, Myers GD, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood (2011) 118:6050-6. doi:10.1182/blood-2011-05-354449.
17. Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med (2011) 3:95ra73. doi:10.1126/scitranslmed.3002842.
18. 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) 368:1509-18. doi:10.1056/NEJMoa1215134.
19. 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) 119:2709-20. doi:10.1182/blood-2011-10-384388.
20. 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. doi:10.1126/scitranslmed.3005930.
21. Zhang JG, Eguchi J, Kruse CA, Gomez GG, Fakhrai H, Schroter S, et al. Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics. Clin Cancer Res (2007) 13:566-75. doi:10.1158/1078-0432.CCR-06-1576.
22. Zhang JG, Kruse CA, Driggers L, Hoa N, Wisoff J, Allen JC, et al. Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy. J Neurooncol (2008) 88:65-76. doi:10.1007/s11060-008-9534-4.
23. Humphrey PA, Wong AJ, Vogelstein B, Zalutsky MR, Fuller GN, Archer GE, et al. Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. Proc Natl Acad Sci U S A (1990) 87:4207-11. doi:10.1073/pnas.87.11.4207.
24. Mintz A, Gibo DM, Slagle-Webb B, Christensen ND, Debinski W. IL-13Ralpha2 is a glioma-restricted receptor for interleukin-13. Neoplasia (2002) 4:388-99. doi:10.1038/sj.neo.7900234.
25. Wykosky J, Gibo DM, Stanton C, Debinski W. EphA2 as a novel molecular marker and target in glioblastoma multiforme. Mol Cancer Res (2005) 3:541-51. doi:10.1158/1541-7786.MCR-05-0056.
26. Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, et al. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res (2002) 62:3347-50.
27. Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A, McLendon RE, et al. Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol (2008) 10:10-8. doi:10.1215/15228517-2007-035.
28. Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R. Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol (2008) 116:79-86. doi:10.1007/s00401-008-0359-1.
29. Uttenthal BJ, Chua I, Morris EC, Stauss HJ. Challenges in T cell receptor gene therapy. J Gene Med (2012) 14:386-99. doi:10.1002/jgm.2637.
30. Cohen CJ, Li YF, El-Gamil M, Robbins PF, Rosenberg SA, Morgan RA. Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res (2007) 67:3898-903. doi:10.1158/0008-5472.CAN-06-3986.
31. Goff SL, Johnson LA, Black MA, Xu H, Zheng Z, Cohen CJ, et al. Enhanced receptor expression and in vitro effector function of a murine-human hybrid MART-1-reactive T cell receptor following a rapid expansion. Cancer Immunol Immunother (2010) 59:1551-60. doi:10.1007/s00262-010-0882-5.
32. Torikai H, Reik A, Liu PQ, Zhou Y, Zhang L, Maiti S, et al. 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 (2012) 119:5697-705. doi:10.1182/blood-2012-01-405365.
33. Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, et al. Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res (2009) 69:9003-11. doi:10.1158/0008-5472.CAN-09-1450.
34. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science (2006) 314:126-9. doi:10.1126/science.1129003.
35. Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, et al. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother (2013) 36:133-51. doi:10.1097/CJI.0b013e3182829903.
36. Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DA, Feldman SA, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther (2011) 19:620-6. doi:10.1038/mt.2010.272.
37. Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol (2011) 29:917-24. doi:10.1200/JCO.2010.32.2537.
38. Levine BL, Rapoport AP, Stadtmauer EA, Vogl DT, Weiss B, Binder-Scholl GK, et al. Safety and correlates of clinical response in an early phase clinical trial in multiple myeloma patients post auto-SCT and adoptive immunotherapy with engineered T cells expressing an HLA-A2 restricted affinity-enhanced TCR for LAGE-1 and NY-ESO-1. Mol Ther (2013) 21:S114.
39. Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL, Emery L, et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood (2013) 122:863-71. doi:10.1182/blood-2013-03-490565.
40. Maher J. Immunotherapy of malignant disease using chimeric antigen receptor engrafted T cells. ISRN Oncol (2012) 2012:278093. doi:10.5402/2012/278093.
41. Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer Discov (2013) 3:388-98. doi:10.1158/2159-8290.CD-12-0548.
42. Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A (1993) 90:720-4. doi:10.1073/pnas.90.2.720.
43. Kahlon KS, Brown C, Cooper LJ, Raubitschek A, Forman SJ, Jensen MC. Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells. Cancer Res (2004) 64:9160-6. doi:10.1158/0008-5472.CAN-04-0454.
44. Shaffer DR, Savoldo B, Yi Z, Chow KK, Kakarla S, Spencer DM, et al. T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. Blood (2011) 117:4304-14. doi:10.1182/blood-2010-04-278218.
45. Davies DM, Foster J, Van Der Stegen SJ, Parente-Pereira AC, Chiapero-Stanke L, Delinassios GJ, et al. Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells. Mol Med (2012) 18:565-76. doi:10.2119/molmed.2011.00493.
46. Zhang T, Lemoi BA, Sentman CL. Chimeric NK-receptor-bearing T cells mediate antitumor immunotherapy. Blood (2005) 106:1544-51. doi:10.1182/blood-2004-11-4365.
47. Hudecek M, Lupo-Stanghellini MT, Kosasih PL, Sommermeyer D, Jensen MC, Rader C, et al. Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T-cells. Clin Cancer Res (2013) 19(12):3153-64. doi:10.1158/1078-0432.CCR-13-0330.
48. Bridgeman JS, Hawkins RE, Bagley S, Blaylock M, Holland M, Gilham DE. The optimal antigen response of chimeric antigen receptors harboring the CD3zeta transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR/CD3 complex. J Immunol (2010) 184:6938-49. doi:10.4049/jimmunol.0901766.
49. Svendsen A, Verhoeff JJ, Immervoll H, Brøgger JC, Kmiecik J, Poli A, et al. Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma. Acta Neuropathol (2011) 122:495-510. doi:10.1007/s00401-011-0867-2.
50. Friese MA, Platten M, Lutz SZ, Naumann U, Aulwurm S, Bischof F, et al. MICA/NKG2D-mediated immunogene therapy of experimental gliomas. Cancer Res (2003) 63:8996-9006.
51. Wilkie S, van Schalkwyk MC, Hobbs S, Davies DM, van der Stegen SJ, Pereira AC, et al. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J Clin Immunol (2012) 32:1059-70. doi:10.1007/s10875-012-9689-9.
52. Kloss CC, Condomines M, Cartellieri M, Bachmann M, Sadelain M. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol (2013) 31:71-5. doi:10.1038/nbt.2459.
53. Lanitis E, Poussin M, Klattenhoff AW, Song D, Sandaltzopoulos R, June CH, et al. Chimeric antigen receptor T cells with dissociated signaling domains exhibit focused antitumor activity with reduced potential for toxicity in vivo. Cancer Immunol Res (2013). doi:10.1158/2326-6066.CIR-13-0008.
54. Grada Z, Hegde M, Byrd T, Shaffer DR, Ghazi A, Brawley VS, et al. TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids (2013) 2:e105. doi:10.1038/mtna.2013.32.
55. Gottschalk S, Ng CYC, Perez M, Smith CA, Sample C, Brenner MK, et al. An Epstein-Barr virus deletion mutant that causes fatal lymphoproliferative disease unresponsive to virus-specific T cell therapy. Blood (2001) 97:835-43. doi:10.1182/blood.V97.4.835.
56. Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci U S A (2002) 99:16168-73. doi:10.1073/pnas.242600099.
57. Bullain SS, Sahin A, Szentirmai O, Sanchez C, Lin N, Baratta E, et al. Genetically engineered T cells to target EGFRvIII expressing glioblastoma. J Neurooncol (2009) 94(3):373-82. doi:10.1007/s11060-009-9889-1.
58. Choi BD, Suryadevara CM, Gedeon PC, Herndon IiJE, Sanchez-Perez L, Bigner DD, et al. Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma. J Clin Neurosci (2013) 21(1):189-90. doi:10.1016/j.jocn.2013.03.012.
59. Chow KK, Naik S, Kakarla S, Brawley VS, Shaffer DR, Yi Z, et al. T cells redirected to EphA2 for the immunotherapy of glioblastoma. Mol Ther (2013) 21:629-37. doi:10.1038/mt.2012.210.
60. Ahmed N, Salsman VS, Kew Y, Shaffer D, Powell S, Zhang YJ, et al. HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors. Clin Cancer Res (2010) 16:474-85. doi:10.1158/1078-0432.CCR-09-1322.
61. Kong S, Sengupta S, Tyler B, Bais AJ, Ma Q, Doucette S, et al. Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells. Clin Cancer Res (2012) 18:5949-60. doi:10.1158/1078-0432.CCR-12-0319.
62. Brown CE, Starr R, Naranjo A, Wright C, Bading J, Ressler JA, et al. Adoptive transfer of autologous IL13-zetakine+ engineered T cell clones for the treatment of recurrent glioblastoma: lessons from the clinic. Mol Ther (2011) 19:S136-7.
63. Brown CE, Starr R, Aguilar B, Shami AF, Martinez C, D'Apuzzo M, et al. Stem-like tumor initiating cells isolated from IL13Ralpha2-expressing gliomas are targeted and killed by IL13-zetakine redirected T cells. Clin Cancer Res (2012) 18(8):2199-209. doi:10.1158/1078-0432.CCR-11-1669.
64. Morgan RA, Johnson LA, Davis JL, Zheng Z, Woolard KD, Reap EA, et al. Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Hum Gene Ther (2012) 23:1043-53. doi:10.1089/hum.2012.041.
65. Hegde M, Corder A, Chow KKh, Mukherjee M, Ashoori A, Kew Y, et al. Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma. Mol Ther (2013) 21:2087-101. doi:10.1038/mt.2013.185.
66. Niederman TM, Ghogawala Z, Carter BS, Tompkins HS, Russell MM, Mulligan RC. Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors. Proc Natl Acad Sci U S A (2002) 99:7009-14. doi:10.1073/pnas.092562399.
67. Chinnasamy D, Yu Z, Theoret MR, Zhao Y, Shrimali RK, Morgan RA, et al. Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice. J Clin Invest (2010) 120:3953-68. doi:10.1172/JCI43490.
68. Chinnasamy D, Tran E, Yu Z, Morgan RA, Restifo NP, Rosenberg SA. Simultaneous targeting of tumor antigens and the tumor vasculature using T lymphocyte transfer synergize to induce regression of established tumors in mice. Cancer Res (2013) 73:3371-80. doi:10.1158/0008-5472.CAN-12-3913.
69. Chinnasamy D, Yu Z, Kerkar SP, Zhang L, Morgan RA, Restifo NP, et al. Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin Cancer Res (2012) 18:1672-83. doi:10.1158/1078-0432.CCR-11-3050.
70. Yaghoubi SS, Jensen MC, Satyamurthy N, Budhiraja S, Paik D, Czernin J, et al. Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nat Clin Pract Oncol (2009) 6:53-8. doi:10.1038/ncponc1278.
71. Wei J, Barr J, Kong LY, Wang Y, Wu A, Sharma AK, et al. Glioma-associated cancer-initiating cells induce immunosuppression. Clin Cancer Res (2010) 16:461-73. doi:10.1158/1078-0432.CCR-09-1983.
72. Gajewski TF, Meng Y, Blank C, Brown I, Kacha A, Kline J, et al. Immune resistance orchestrated by the tumor microenvironment. Immunol Rev (2006) 213:131-45. doi:10.1111/j.1600-065X.2006.00442.x.
73. Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol (2007) 25:267-96. doi:10.1146/annurev.immunol.25.022106.141609.
74. Carpenito C, Milone MC, Hassan R, Simonet JC, Lakhal M, Suhoski MM, et al. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci U S A (2009) 106:3360-5. doi:10.1073/pnas.0813101106.
75. Brentjens RJ, Latouche JB, Santos E, Marti F, Gong MC, Lyddane C, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat Med (2003) 9:279-86. doi:10.1038/nm827.
76. Stephan MT, Ponomarev V, Brentjens RJ, Chang AH, Dobrenkov KV, Heller G, et al. T cell-encoded CD80 and 4-1BBL induce auto-and transcostimulation, resulting in potent tumor rejection. Nat Med (2007) 13:1440-9. doi:10.1038/nm1676.
77. Pule MA, Straathof KC, Dotti G, Heslop HE, Rooney CM, Brenner MK. A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther (2005) 12:933-41. doi:10.1016/j.ymthe.2005.04.016.
78. 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) 121:1822-6. doi:10.1172/JCI46110.
79. Rooney CM, Smith CA, Ng CY, Loftin SK, Sixbey JW, Gan Y, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood (1998) 92:1549-55.
80. Heslop HE, Slobod KS, Pule MA, Hale GA, Rousseau A, Smith CA, et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood (2010) 115:925-35. doi:10.1182/blood-2009-08-239186.
81. Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol (2008) 26:5233-9. doi:10.1200/JCO.2008.16.5449.
82. Cooper LJ, Al Kadhimi Z, Serrano LM, Pfeiffer T, Olivares S, Castro A, et al. Enhanced antilymphoma efficacy of CD19-redirected influenza MP1-specific CTLs by cotransfer of T cells modified to present influenza MP1. Blood (2005) 105:1622-31. doi:10.1182/blood-2004-03-1208.
83. Terakura S, Yamamoto TN, Gardner RA, Turtle CJ, Jensen MC, Riddell SR. Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells. Blood (2012) 119:72-82. doi:10.1182/blood-2011-07-366419.
84. Berger C, Jensen MC, Lansdorp PM, Gough M, Elliott C, Riddell SR. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest (2008) 118:294-305. doi:10.1172/JCI32103.
85. Kerkar SP, Leonardi AJ, van Panhuys N, Zhang L, Yu Z, Crompton JG, et al. Collapse of the tumor stroma is triggered by IL-12 induction of Fas. Mol Ther (2013) 21:1369-77. doi:10.1038/mt.2013.58.
86. Zhang L, Kerkar SP, Yu Z, Zheng Z, Yang S, Restifo NP, et al. Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment. Mol Ther (2011) 19:751-9. doi:10.1038/mt.2010.313.
87. Quintarelli C, Vera JF, Savoldo B, Giordano Attianese GM, Pule M, Foster AE, et al. Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes. Blood (2007) 110:2793-802. doi:10.1182/blood-2007-02-072843.
88. Hoyos V, Savoldo B, Quintarelli C, Mahendravada A, Zhang M, Vera J, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia (2010) 24:1160-70. doi:10.1038/leu.2010.75.
89. Perna SK, De Angelis B, Pagliara D, Hasan ST, Zhang L, Mahendravada A, et al. Interleukin 15 provides relief to CTLs from regulatory T cell-mediated inhibition: implications for adoptive T cell-based therapies for lymphoma. Clin Cancer Res (2013) 19:106-17. doi:10.1158/1078-0432.CCR-12-2143.
90. Dotti G, Savoldo B, Pule M, Straathof KC, Biagi E, Yvon E, et al. Human cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosis. Blood (2005) 105:4677-84. doi:10.1182/blood-2004-08-3337.
91. Peggs KS, Quezada SA, Allison JP. Cancer immunotherapy: co-stimulatory agonists and co-inhibitory antagonists. Clin Exp Immunol (2009) 157:9-19. doi:10.1111/j.1365-2249.2009.03912.x.
92. Yang L, Pang Y, Moses HL. TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol (2010) 31:220-7. doi:10.1016/j.it.2010.04.002.
93. Bollard CM, Rössig C, Calonge MJ, Huls MH, Wagner HJ, Massague J, et al. Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood (2002) 99:3179-87. doi:10.1182/blood.V99.9.3179.
94. Foster AE, Dotti G, Lu A, Khalil M, Brenner MK, Heslop HE, et al. Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor. J Immunother (2008) 31:500-5. doi:10.1097/CJI.0b013e318177092b.
95. Bollard CM, Dotti G, Gottschalk S, Mims M, Liu H, Gee AP, et al. Administration of TGF-beta resistant tumor-specific CTL to patients with EBV-associated HL and NHL. Mol Ther (2012) 20:S22.
96. Wilkie S, Burbridge SE, Chiapero-Stanke L, Pereira AC, Cleary S, van der Stegen SJ, et al. Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. J Biol Chem (2010) 285:25538-44. doi:10.1074/jbc.M110.127951.
97. Leen AM, Katari U, Kerinan J, Rooney CM, Brenner MK, Vera JF Improved expansion and anti-tumor activity of tumor-specific CTLs using a transgenic chimeric cytokine receptor. Mol Ther (2011) 19:S194.
98. Watanabe N, Anurathapan U, Brenner MK, Heslop HE, Leen AM, Rooney CM, et al. Transgenic expression of a novel immunosuppressive signal converter on T cells. Mol Ther (2013) 22:S153.
99. Sun J, Dotti G, Huye LE, Foster AE, Savoldo B, Gramatges MM, et al. T cells expressing constitutively active Akt resist multiple tumor-associated inhibitory mechanisms. Mol Ther (2010) 18:2006-17. doi:10.1038/mt.2010.185.
100. Pakakasama S, Eames GM, Morriss MC, Huls MH, Rooney CM, Heslop HE, et al. Treatment of Epstein-Barr virus lymphoproliferative disease after hematopoietic stem-cell transplantation with hydroxyurea and cytotoxic T-cell lymphocytes. Transplantation (2004) 78:755-7. doi:10.1097/01.TP.0000129813.54517.25.
101. Hong JJ, Rosenberg SA, Dudley ME, Yang JC, White DE, Butman JA, et al. Successful treatment of melanoma brain metastases with adoptive cell therapy. Clin Cancer Res (2010) 16:4892-8. doi:10.1158/1078-0432.CCR-10-1507.
102. Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA, et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res (2006) 12:6106-15. doi:10.1158/1078-0432.CCR-06-1183.
103. Craddock JA, Lu A, Bear A, Pule M, Brenner MK, Rooney CM, et al. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. J Immunother (2010) 33(8):780-8. doi:10.1097/CJI.0b013e3181ee6675.
104. Kershaw MH, Wang G, Bear A, Pule M, Brenner MK, Rooney CM, et al. Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2. Hum Gene Ther (2002) 13:1971-80. doi:10.1089/10430340260355374.
105. Bonini C, Brenner MK, Heslop HE, Morgan RA. Genetic modification of T cells. Biol Blood Marrow Transplant (2011) 17:S15-20. doi:10.1016/j.bbmt.2010.09.019.
106. 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:e20-2. doi:10.1200/JCO.2006.05.9964.
107. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med (2011) 365:725-33. doi:10.1056/NEJMoa1103849.
108. Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M, et al. 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 Oncol (2009) 10:489-500. doi:10.1016/S1470-2045(09)70074-9.
109. Straathof KC, Pulè MA, Yotnda P, Dotti G, Vanin EF, Brenner MK, et al. An inducible caspase 9 safety switch for T-cell therapy. Blood (2005) 105:4247-54. doi:10.1182/blood-2004-11-4564.
110. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med (2011) 365:1673-83. doi:10.1056/NEJMoa1106152.
111. Introna M, Barbui AM, Bambacioni F, Casati C, Gaipa G, Borleri G, et al. Genetic modification of human T cells with CD20: a strategy to purify and lyse transduced cells with anti-CD20 antibodies. Hum Gene Ther (2000) 11:611-20. doi:10.1089/10430340050015798.
112. Gardner RA, Reik A, Berger C, Terakura S, Gregory PD, Jensen CM et al. Disruption of glucocorticoid regulation in therapeutic human T cells with zinc finger nucleases. Mol Ther (2010) 18:S240.
113. Lamb LS Jr, Bowersock J, Dasgupta A, Gillespie GY, Su Y, Johnson A, et al. Engineered drug resistant gammadelta T cells kill glioblastoma cell lines during a chemotherapy challenge: a strategy for combining chemo-and immunotherapy. PLoS One (2013) 8:e51805. doi:10.1371/journal.pone.0051805.