• 1
    Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer 2012; 12: 27887.
  • 2
    Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 2008; 8: 299308.
  • 3
    Morgan RA, Dudley ME, Wunderlich JR et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 1269.
  • 4
    Kalos M, Levine BL, Porter DL 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.
  • 5
    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: 72533.
  • 6
    Clay TM, Custer MC, Sachs J, Hwu P, Rosenberg SA, Nishimura MI. Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity. J Immunol 1999; 163: 50713.
  • 7
    Stanislawski T, Voss RH, Lotz C et al. Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer. Nat Immunol 2001; 2: 96270.
  • 8
    Morgan RA, Dudley ME, Yu YY et al. High efficiency TCR gene transfer into primary human lymphocytes affords avid recognition of melanoma tumor antigen glycoprotein 100 and does not alter the recognition of autologous melanoma antigens. J Immunol 2003; 171: 328795.
  • 9
    Schaft N, Willemsen RA, de Vries J et al. Peptide fine specificity of anti-glycoprotein 100 CTL is preserved following transfer of engineered TCR alpha beta genes into primary human T lymphocytes. J Immunol 2003; 170: 218694.
  • 10
    Zhao Y, Zheng Z, Robbins PF, Khong HT, Rosenberg SA, Morgan RA. Primary human lymphocytes transduced with NY-ESO-1 antigen-specific TCR genes recognize and kill diverse human tumor cell lines. J Immunol 2005; 174: 441523.
  • 11
    Cohen CJ, Zheng Z, Bray R et al. Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine anti-p53 TCR. J Immunol 2005; 175: 5799808.
  • 12
    Parkhurst MR, Joo J, Riley JP et al. Characterization of genetically modified T-cell receptors that recognize the CEA:691–699 peptide in the context of HLA-A2.1 on human colorectal cancer cells. Clin Cancer Res 2009; 15: 16980.
  • 13
    Johnson LA, Morgan RA, Dudley ME et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009; 114: 53546.
  • 14
    Frankel TL, Burns WR, Peng PD et al. Both CD4 and CD8 T cells mediate equally effective in vivo tumor treatment when engineered with a highly avid TCR targeting tyrosinase. J Immunol 2010; 184: 598898.
  • 15
    Chinnasamy N, Wargo JA, Yu Z et al. A TCR targeting the HLA-A*0201-restricted epitope of MAGE-A3 recognizes multiple epitopes of the MAGE-A antigen superfamily in several types of cancer. J Immunol 2011; 186: 68596.
  • 16
    Straetemans T, van Brakel M, van Steenbergen S et al. TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma-specific immune targets. Clin Dev Immunol 2012; 2012: 586314.
  • 17
    Hillerdal V, Nilsson B, Carlsson B, Eriksson F, Essand M. T cells engineered with a T cell receptor against the prostate antigen TARP specifically kill HLA-A2+ prostate and breast cancer cells. Proc Natl Acad Sci U S A 2012; 109: 1587781.
  • 18
    Tsuji T, Yasukawa M, Matsuzaki J et al. Generation of tumor-specific, HLA class I-restricted human Th1 and Tc1 cells by cell engineering with tumor peptide-specific T-cell receptor genes. Blood 2005; 106: 4706.
  • 19
    Johnson LA, Heemskerk B, Powell DJ Jr et al. Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes. J Immunol 2006; 177: 654859.
  • 20
    Scholten KB, Kramer D, Kueter EW et al. Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells. Clin Immunol 2006; 119: 13545.
  • 21
    Hart DP, Xue SA, Thomas S et al. Retroviral transfer of a dominant TCR prevents surface expression of a large proportion of the endogenous TCR repertoire in human T cells. Gene Ther 2008; 15: 62531.
  • 22
    Szymczak AL, Workman CJ, Wang Y et al. Correction of multi-gene deficiency in vivo using a single ‘self-cleaving’ 2A peptide-based retroviral vector. Nat Biotechnol 2004; 22: 58994.
  • 23
    Ahmadi M, King JW, Xue SA et al. CD3 limits the efficacy of TCR gene therapy in vivo. Blood 2011; 118: 352837.
  • 24
    Cohen CJ, Zhao Y, Zheng Z, Rosenberg SA, Morgan RA. Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability. Cancer Res 2006; 66: 887886.
  • 25
    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: 3898903.
  • 26
    Kuball J, Dossett ML, Wolfl M et al. Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 2007; 109: 23318.
  • 27
    Voss RH, Willemsen RA, Kuball J et al. Molecular design of the Calphabeta interface favors specific pairing of introduced TCRalphabeta in human T cells. J Immunol 2008; 180: 391401.
  • 28
    Okamoto S, Mineno J, Ikeda 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: 900311.
  • 29
    Ochi T, Fujiwara H, Okamoto S et al. Novel adoptive T-cell immunotherapy using a WT1-specific TCR vector encoding silencers for endogenous TCRs shows marked antileukemia reactivity and safety. Blood 2011; 118: 1495503.
  • 30
    Provasi E, Genovese P, Lombardo A et al. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat Med 2012; 18: 80715.
  • 31
    Aleksic M, Liddy N, Molloy PE et al. Different affinity windows for virus and cancer-specific T-cell receptors: implications for therapeutic strategies. Eur J Immunol 2012. Sept 5 [Epub ahead of print].
  • 32
    Li LP, Lampert JC, Chen X et al. Transgenic mice with a diverse human T cell antigen receptor repertoire. Nat Med 2010; 16: 102934.
  • 33
    Sadovnikova E, Jopling LA, Soo KS, Stauss HJ. Generation of human tumor-reactive cytotoxic T cells against peptides presented by non-self HLA class I molecules. Eur J Immunol 1998; 28: 193200.
  • 34
    Gao L, Bellantuono I, Elsasser A et al. Selective elimination of leukemic CD34(+) progenitor cells by cytotoxic T lymphocytes specific for WT1. Blood 2000; 95: 2198203.
  • 35
    Amir AL, van der Steen DM, van Loenen MM et al. PRAME-specific Allo-HLA-restricted T cells with potent antitumor reactivity useful for therapeutic T-cell receptor gene transfer. Clin Cancer Res 2011; 17: 561525.
  • 36
    Kieke MC, Sundberg E, Shusta EV, Mariuzza RA, Wittrup KD, Kranz DM. High affinity T cell receptors from yeast display libraries block T cell activation by superantigens. J Mol Biol 2001; 307: 130515.
  • 37
    Li Y, Moysey R, Molloy PE et al. Directed evolution of human T-cell receptors with picomolar affinities by phage display. Nat Biotechnol 2005; 23: 34954.
  • 38
    Robbins PF, Li YF, El-Gamil M et al. Single and dual amino acid substitutions in TCR CDRs can enhance antigen-specific T cell functions. J Immunol 2008; 180: 611631.
  • 39
    Alli R, Zhang ZM, Nguyen P, Zheng JJ, Geiger TL. Rational design of T cell receptors with enhanced sensitivity for antigen. PLoS ONE 2011; 6: e18027.
  • 40
    Liddy N, Bossi G, Adams KJ et al. Monoclonal TCR-redirected tumor cell killing. Nat Med 2012; 119: 342030.
  • 41
    Dahan R, Reiter Y. T-cell-receptor-like antibodies - generation, function and applications. Expert Rev Mol Med 2012; 14: e6.
  • 42
    Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A 1989; 86: 100248.
  • 43
    Finney HM, Lawson AD, Bebbington CR, Weir AN. Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol 1998; 161: 27917.
  • 44
    Brentjens RJ, Latouche JB, Santos E 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: 27986.
  • 45
    Imai C, Mihara K, Andreansky M et al. Chimeric receptors with 4–1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia 2004; 18: 67684.
  • 46
    Lamers CH, Sleijfer S, Vulto AG 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: e202.
  • 47
    Till BG, Jensen MC, Wang J et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood 2008; 112: 226171.
  • 48
    Zhao Y, Wang QJ, Yang S et al. A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity. J Immunol 2009; 183: 556374.
  • 49
    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: 84351.
  • 50
    Krause A, Guo HF, Latouche JB, Tan C, Cheung NK, Sadelain M. Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J Exp Med 1998; 188: 61926.
  • 51
    Pule MA, Savoldo B, Myers GD et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med 2008; 14: 126470.
  • 52
    Gong MC, Latouche JB, Krause A, Heston WD, Bander NH, Sadelain M. Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen. Neoplasia 1999; 1: 1237.
  • 53
    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: 705.
  • 54
    Katari UL, Keirnan JM, Worth AC et al. Engineered T cells for pancreatic cancer treatment. HPB (Oxford) 2011; 13: 64350.
  • 55
    Zheng Z, Chinnasamy N, Morgan RA. Protein L: a novel reagent for the detection of chimeric antigen receptor (CAR) expression by flow cytometry. J Transl Med 2012; 10: 29.
  • 56
    Carpenito C, Milone MC, Hassan R 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: 33605.
  • 57
    Park JR, Digiusto DL, Slovak M et al. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol Ther 2007; 15: 82533.
  • 58
    Chinnasamy D, Yu Z, Theoret MR 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: 395368.
  • 59
    Chekmasova AA, Rao TD, Nikhamin Y et al. Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen. Clin Cancer Res 2010; 16: 3594606.
  • 60
    Kershaw MH, Westwood JA, Parker LL et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 2006; 12: 610615.
  • 61
    Song DG, Ye Q, Carpenito C et al. In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4–1BB). Cancer Res 2011; 71: 461727.
  • 62
    Lanitis E, Poussin M, Hagemann IS et al. Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor. Mol Ther 2012; 20: 63343.
  • 63
    Brocker T, Karjalainen K. Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes. J Exp Med 1995; 181: 16539.
  • 64
    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: 10413.
  • 65
    Loskog A, Giandomenico V, Rossig C, Pule M, Dotti G, Brenner MK. Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. Leukemia 2006; 20: 181928.
  • 66
    Song DG, Ye Q, Poussin M, Harms GM, Figini M, Powell DJ Jr. CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood 2012; 119: 696706.
  • 67
    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: 93341.
  • 68
    Savoldo B, Ramos CA, Liu E et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 2011; 121: 18226.
  • 69
    Kochenderfer JN, Wilson WH, Janik JE et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 2010; 116: 4099102.
  • 70
    Brentjens RJ, Riviere I, Park JH et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 2011; 118: 481728.
  • 71
    Milone MC, Fish JD, Carpenito C et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther 2009; 17: 145364.
  • 72
    Vera J, Savoldo B, Vigouroux S et al. T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Blood 2006; 108: 38907.
  • 73
    Torikai H, Reik A, Liu PQ 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: 5697705.
  • 74
    Cavalieri S, Cazzaniga S, Geuna M et al. Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence. Blood 2003; 102: 497505.
  • 75
    Sauce D, Tonnelier N, Duperrier A et al. Influence of ex vivo expansion and retrovirus-mediated gene transfer on primary T lymphocyte phenotype and functions. J Hematother Stem Cell Res 2002; 11: 92940.
  • 76
    Rans TS, England R. The evolution of gene therapy in X-linked severe combined immunodeficiency. Ann Allergy Asthma Immunol 2009; 102: 35762; quiz 363-355, 402.
  • 77
    Newrzela S, Cornils K, Heinrich T et al. Retroviral insertional mutagenesis can contribute to immortalization of mature T lymphocytes. Mol Med 2011; 17: 122332.
  • 78
    Biffi A, Bartolomae CC, Cesana D et al. Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection. Blood 2011; 117: 53329.
  • 79
    Serrano LM, Pfeiffer T, Olivares S et al. Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy. Blood 2006; 107: 264352.
  • 80
    Zhao Y, Zheng Z, Cohen CJ et al. High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation. Mol Ther 2006; 13: 1519.
  • 81
    Birkholz K, Hombach A, Krug C et al. Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer. Gene Ther 2009; 16: 596604.
  • 82
    Zhao Y, Moon E, Carpenito C et al. Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res 2010; 70: 905361.
  • 83
    Barrett DM, Zhao Y, Liu X et al. Treatment of advanced leukemia in mice with mRNA engineered T cells. Hum Gene Ther 2011; 22: 157586.
  • 84
    Wilson MH, Coates CJ, George AL Jr. PiggyBac transposon-mediated gene transfer in human cells. Mol Ther 2007; 15: 13945.
  • 85
    Hackett PB, Largaespada DA, Cooper LJ. A transposon and transposase system for human application. Mol Ther 2010; 18: 67483.
  • 86
    Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401: 70812.
  • 87
    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: 294305.
  • 88
    Overwijk WW, Theoret MR, Finkelstein SE et al. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J Exp Med 2003; 198: 56980.
  • 89
    Hinrichs CS, Borman ZA, Cassard L et al. Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci U S A 2009; 106: 1746974.
  • 90
    Gattinoni L, Zhong XS, Palmer DC et al. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat Med 2009; 15: 80813.
  • 91
    Gattinoni L, Lugli E, Ji Y et al. A human memory T cell subset with stem cell-like properties. Nat Med 2011; 17: 12907.
  • 92
    Kaneko S, Mastaglio S, Bondanza A et al. IL-7 and IL-15 allow the generation of suicide gene-modified alloreactive self-renewing central memory human T lymphocytes. Blood 2009; 113: 100615.
  • 93
    Savoldo B, Rooney CM, Di Stasi A et al. Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood 2007; 110: 262030.
  • 94
    Wrzesinski C, Paulos CM, Kaiser A et al. Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells. J Immunother 2010; 33: 17.
  • 95
    Muranski P, Boni A, Wrzesinski C et al. Increased intensity lymphodepletion and adoptive immunotherapy–how far can we go? Nat Clin Pract Oncol 2006; 3: 66881.
  • 96
    Dudley ME, Wunderlich JR, Yang JC et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005; 23: 234657.
  • 97
    Yee C, Thompson JA, Byrd D 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: 1616873.
  • 98
    Klapper JA, Downey SG, Smith FO et al. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer 2008; 113: 293301.
  • 99
    Kerkar SP, Muranski P, Kaiser A et al. Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hosts. Cancer Res 2010; 70: 672534.
  • 100
    Klebanoff CA, Gattinoni L, Palmer DC et al. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice. Clin Cancer Res 2011; 17: 534352.
  • 101
    Morgan RA. Human tumor xenografts: the good, the bad, and the ugly. Mol Ther 2012; 20: 8824.
  • 102
    Kershaw MH, Wang G, Westwood JA et al. Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2. Hum Gene Ther 2002; 13: 197180.
  • 103
    Di Stasi A, De Angelis B, Rooney CM et al. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 2009; 113: 6392402.
  • 104
    Bonini C, Bondanza A, Perna SK et al. The suicide gene therapy challenge: how to improve a successful gene therapy approach. Mol Ther 2007; 15: 124852.
  • 105
    Marktel S, Magnani Z, Ciceri F et al. Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell-depleted stem cell transplantation. Blood 2003; 101: 12908.
  • 106
    Straathof KC, Pule MA, Yotnda P et al. An inducible caspase 9 safety switch for T-cell therapy. Blood 2005; 105: 424754.
  • 107
    Di Stasi A, Tey SK, Dotti G et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med 2011; 365: 167383.
  • 108
    Griffioen M, van Egmond EH, Kester MG, Willemze R, Falkenburg JH, Heemskerk MH. Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy. Haematologica 2009; 94: 131620.