Abstract
The unrivaled potential of T cells for targeted immune function is central to the eradication of cancer. While their natural anti-tumor response might sometimes be insufficient, several studies and importantly, multiple clinical trials in terminally-ill cancer patients have demonstrated that it is possible to design novel and efficient immunotherapeutic approaches based on the adoptive transfer of autologous tumor-specific T lymphocytes. Herein, we will expand on the development and the use of such strategies using tumor-infiltrating lymphocytes or genetically-engineered T cells. We will also comment on the requirements and potential hurdles encountered when elaborating and implementing such treatments as well as the exciting prospects for this kind of emerging personalized medicine therapy.
Keywords
- Chimeric Antigen Receptor
- Adoptive Cell Therapy
- Functional Avidity
- Chimeric Immune Receptor
- Autologous TILs
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Abbreviations
- ACT:
-
Adoptive cell transfer
- AICD:
-
Activation-induced T-cell death
- CAIX:
-
Carboxy-anhydrase-IX
- CAR:
-
Chimeric antigen receptor
- CEA:
-
Carcino embryonic antigen
- CT:
-
Cancer/testis
- EBV:
-
Epstein–Barr virus
- HLA:
-
Human leukocyte antigen
- hTERT:
-
Human telomerase reverse transcriptase
- HTLV-1:
-
Human T-cell lymphotrophic virus type I
- IL:
-
Interleukin
- ITAM:
-
Immunoreceptor tyrosine-based activation motif
- MDSC:
-
Myeloid-derived suppressor cell
- MHC:
-
Major histocompatibility complex
- PBL:
-
Peripheral blood lymphocyte
- RCC:
-
Renal cell carcinoma
- scFv:
-
Single-chain variable fragment
- TA:
-
Tumor antigen
- TCR:
-
T-cell receptor
- TGF-β:
-
Transforming growth factor-β
- TIL:
-
Tumor-infiltrating lymphocyte
- Tregs:
-
Regulatory T-cells
References
Zhang N, Bevan MJ (2011) CD8(+) T cells: foot soldiers of the immune system. Immunity 35:161–168
Seremet T, Brasseur F, Coulie PG (2011) Tumor-specific antigens and immunologic adjuvants in cancer immunotherapy. Cancer J 17:325–330
Renkvist N, Castelli C, Robbins PF et al (2001) A listing of human tumor antigens recognized by T cells. Cancer Immunol Immunother 50:3–15
Linnemann C, Schumacher TN, Bendle GM (2011) T-cell receptor gene therapy: critical parameters for clinical success. J Invest Dermatol 131:1806–1816
Simpson AJ, Caballero OL, Jungbluth A et al (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5:615–625
Zur HH (2009) The search for infectious causes of human cancers: where and why. Virology 392:1–10
Fridman WH, Pages F, Sautes-Fridman C et al (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306
Pages F, Galon J, Dieu-Nosjean MC et al (2010) Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 29:1093–1102
Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949
Restifo NP, Dudley ME, Rosenberg SA (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol 12:269–281
Muul LM, Spiess PJ, Director EP et al (1987) Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol 138:989–995
Rosenberg SA, Dudley ME (2009) Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol 21:233–240
Rosenberg SA, Spiess P, Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233:1318–1321
Atkins MB, Lotze MT, Dutcher JP et al (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 17:2105–2116
Rosenberg SA, Yang JC, Sherry RM et al (2011) Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 17:4550–4557
Rosenberg SA, Packard BS, Aebersold PM et al (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 319:1676–1680
Dudley ME, Yang JC, Sherry R et al (2008) Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 26:5233–5239
Gattinoni L, Finkelstein SE, Klebanoff CA et al (2005) Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med 202:907–912
Muranski P, Boni A, Wrzesinski C et al (2006) Increased intensity lymphodepletion and adoptive immunotherapy—how far can we go? Nat Clin Pract Oncol 3:668–681
Robbins PF, Dudley ME, Wunderlich J et al (2004) Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol 173:7125–7130
Zhou J, Dudley ME, Rosenberg SA et al (2005) Persistence of multiple tumor-specific T-cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy. J Immunother 28:53–62
Klebanoff CA, Gattinoni L, Torabi-Parizi P et al (2005) Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci USA 102:9571–9576
Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12:253–268
Kerkar SP, Restifo NP (2012) Cellular constituents of immune escape within the tumor microenvironment. Cancer Res 72:3125–3130
Gattinoni L, Klebanoff CA, Restifo NP (2012) Paths to stemness: building the ultimate antitumour T cell. Nat Rev Cancer 12:671–684
Ogino S, Galon J, Fuchs CS et al (2011) Cancer immunology—analysis of host and tumor factors for personalized medicine. Nat Rev Clin Oncol 8:711–719
Ruffell B, Au A, Rugo HS et al (2012) Leukocyte composition of human breast cancer. Proc Natl Acad Sci USA 109:2796–2801
Walia V, Mu EW, Lin JC et al (2012) Delving into somatic variation in sporadic melanoma. Pigment Cell Melanoma Res 25:155–170
Biswas K, Richmond A, Rayman P et al (2006) GM2 expression in renal cell carcinoma: potential role in tumor-induced T-cell dysfunction. Cancer Res 66:6816–6825
Storkel S, Keymer R, Steinbach F et al (1992) Reaction patterns of tumor infiltrating lymphocytes in different renal cell carcinomas and oncocytomas. Prog Clin Biol Res 378:217–223
Uzzo RG, Rayman P, Kolenko V et al (1999) Renal cell carcinoma-derived gangliosides suppress nuclear factor-kappaB activation in T cells. J Clin Invest 104:769–776
Zhang J, Chen Y, Li J et al (2006) Renal tubular epithelial expression of the coinhibitory molecule B7-DC (programmed death-1 ligand). J Nephrol 19:429–438
Goedegebuure PS, Douville LM, Li H et al (1995) Adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 in patients with metastatic malignant melanoma and renal cell carcinoma: a pilot study. J Clin Oncol 13:1939–1949
Markel G, Cohen-Sinai T, Besser MJ et al (2009) Preclinical evaluation of adoptive cell therapy for patients with metastatic renal cell carcinoma. Anticancer Res 29:145–154
Dudley ME, Wunderlich JR, Shelton TE et al (2003) Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother 26:332–342
Besser MJ, Shapira-Frommer R, Treves AJ et al (2010) Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res 16:2646–2655
Tran KQ, Zhou J, Durflinger KH et al (2008) Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy. J Immunother 31:742–751
Dudley ME, Gross CA, Langhan MM et al (2010) CD8+ enriched “young” tumor infiltrating lymphocytes can mediate regression of metastatic melanoma. Clin Cancer Res 16(24):6122–6131
Hershkovitz L, Schachter J, Treves AJ et al (2010) Focus on adoptive T cell transfer trials in melanoma. Clin Dev Immunol 2010:260267
Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454
Gattinoni L, Zhong XS, Palmer DC et al (2009) Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat Med 15:808–813
Hinrichs CS, Spolski R, Paulos CM et al (2008) IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood 111:5326–5333
Kerkar SP, Muranski P, Kaiser A et al (2010) Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hosts. Cancer Res 70:6725–6734
Klebanoff CA, Finkelstein SE, Surman DR et al (2004) IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci USA 101:1969–1974
Pellegrini M, Calzascia T, Elford AR et al (2009) Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nat Med 15:528–536
Pouw N, Treffers-Westerlaken E, Kraan J et al (2010) Combination of IL-21 and IL-15 enhances tumour-specific cytotoxicity and cytokine production of TCR-transduced primary T cells. Cancer Immunol Immunother 59:921–931
Refaeli Y, Van Parijs L, London CA et al (1998) Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis. Immunity 8:615–623
Dembic Z, Haas W, Weiss S et al (1986) Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature 320:232–238
Clay TM, Custer MC, Sachs J et al (1999) Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity. J Immunol 163:507–513
Kessels HW, Wolkers MC, van dB et al (2001) Immunotherapy through TCR gene transfer. Nat Immunol 2:957–961
Morgan RA, Dudley ME, Wunderlich JR et al (2006) Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126–129
Johnson LA, Morgan RA, Dudley ME 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
Davis JL, Theoret MR, Zheng Z et al (2010) Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials. Clin Cancer Res 16:5852–5861
Robbins PF, Morgan RA, Feldman SA et al (2011) Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 29:917–924
Parkhurst MR, Yang JC, Langan RC et al (2011) T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther 19:620–626
Jager E, Chen YT, Drijfhout JW et al (1998) Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes. J Exp Med 187:265–270
Metzker ML (2010) Sequencing technologies — the next generation. Nat Rev Genet 11:31–46
Warren RL, Holt RA (2010) A census of predicted mutational epitopes suitable for immunologic cancer control. Hum Immunol 71:245–254
Dudley ME, Wunderlich JR, Yang JC et al (2005) Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 23:2346–2357
Yee C, Thompson JA, Byrd D et al (2002) 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 USA 99:16168–16173
Kaluza KM, Thompson JM, Kottke TJ et al (2012) Adoptive T cell therapy promotes the emergence of genomically altered tumor escape variants. Int J Cancer 131:844–854
Dudley ME, Wunderlich JR, Robbins PF et al (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850–854
Amir AL, van der Steen DM, van Loenen MM et al (2011) PRAME-specific Allo-HLA-restricted T cells with potent antitumor reactivity useful for therapeutic T-cell receptor gene transfer. Clin Cancer Res 17:5615–5625
Sadovnikova E, Stauss HJ (1996) Peptide-specific cytotoxic T lymphocytes restricted by nonself major histocompatibility complex class I molecules: reagents for tumor immunotherapy. Proc Natl Acad Sci USA 93:13114–13118
Savage P, Gao L, Vento K et al (2004) Use of B cell-bound HLA-A2 class I monomers to generate high-avidity, allo-restricted CTLs against the leukemia-associated protein Wilms tumor antigen. Blood 103:4613–4615
Chinnasamy N, Wargo JA, Yu Z et al (2011) 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 186:685–696
Cohen CJ, Zheng Z, Bray R et al (2005) Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine anti-p53 TCR. J Immunol 175:5799–5808
Parkhurst MR, Joo J, Riley JP et al (2009) 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 15:169–180
Theobald M, Biggs J, Dittmer D et al (1995) Targeting p53 as a general tumor antigen. Proc Natl Acad Sci USA 92:11993–11997
Chlewicki LK, Holler PD, Monti BC et al (2005) High-affinity, peptide-specific T cell receptors can be generated by mutations in CDR1, CDR2 or CDR3. J Mol Biol 346:223–239
Holler PD, Holman PO, Shusta EV et al (2000) In vitro evolution of a T cell receptor with high affinity for peptide/MHC. Proc Natl Acad Sci USA 97:5387–5392
Kessels HW, van dB, Spits H et al (2000) Changing T cell specificity by retroviral T cell receptor display. Proc Natl Acad Sci USA 97:14578–14583
Li Y, Moysey R, Molloy PE et al (2005) Directed evolution of human T-cell receptors with picomolar affinities by phage display. Nat Biotechnol 23:349–354
Zhao Y, Bennett AD, Zheng Z et al (2007) High-affinity TCRs generated by phage display provide CD4+ T cells with the ability to recognize and kill tumor cell lines. J Immunol 179:5845–5854
Li LP, Lampert JC, Chen X et al (2010) Transgenic mice with a diverse human T cell antigen receptor repertoire. Nat Med 16:1029–1034
Hughes MS, Yu YY, Dudley ME et al (2005) Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions. Hum Gene Ther 16:457–472
Riviere I, Brose K, Mulligan RC (1995) Effects of retroviral vector design on expression of human adenosine deaminase in murine bone marrow transplant recipients engrafted with genetically modified cells. Proc Natl Acad Sci USA 92:6733–6737
Schambach A, Swaney WP, van der Loo JC (2009) Design and production of retro- and lentiviral vectors for gene expression in hematopoietic cells. Methods Mol Biol 506:191–205
Yang S, Cohen CJ, Peng PD et al (2008) Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition. Gene Ther 15:1411–1423
Yang S, Rosenberg SA, Morgan RA (2008) Clinical-scale lentiviral vector transduction of PBL for TCR gene therapy and potential for expression in less-differentiated cells. J Immunother 31:830–839
Peng PD, Cohen CJ, Yang S et al (2009) Efficient nonviral Sleeping Beauty transposon-based TCR gene transfer to peripheral blood lymphocytes confers antigen-specific antitumor reactivity. Gene Ther 16:1042–1049
Williams DA (2008) Sleeping beauty vector system moves toward human trials in the United States. Mol Ther 16:1515–1516
Huang X, Wilber AC, Bao L et al (2006) Stable gene transfer and expression in human primary T cells by the Sleeping Beauty transposon system. Blood 107:483–491
Ivics Z, Hackett PB, Plasterk RH et al (1997) Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91:501–510
Zhao Y, Moon E, Carpenito C et al (2010) Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor. Cancer Res 70:9053–9061
Govers C, Sebestyen Z, Coccoris M et al (2010) T cell receptor gene therapy: strategies for optimizing transgenic TCR pairing. Trends Mol Med 16:77–87
Bendle GM, Linnemann C, Hooijkaas AI et al (2010) Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat Med 16:565–570
Daniel-Meshulam I, Ya’acobi S, Ankri C et al (2012) How (specific) would like your T-cells today? Generating T-cell therapeutic function through TCR-gene transfer. Front Immunol 3:186
Bialer G, Horovitz-Fried M, Ya’acobi S et al (2010) Selected murine residues endow human TCR with enhanced tumor recognition. J Immunol 184:6232–6241
Cohen CJ, Zhao Y, Zheng Z et al (2006) 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 66:8878–8886
Sommermeyer D, Uckert W (2010) Minimal amino acid exchange in human TCR constant regions fosters improved function of TCR gene-modified T cells. J Immunol 184:6223–6231
Stanislawski T, Voss RH, Lotz C et al (2001) Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer. Nat Immunol 2:962–970
Thomas S, Xue SA, Cesco-Gaspere M et al (2007) Targeting the Wilms tumor antigen 1 by TCR gene transfer: TCR variants improve tetramer binding but not the function of gene modified human T cells. J Immunol 179:5803–5810
Cohen CJ, Li YF, El Gamil M et al (2007) Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res 67:3898–3903
Kuball J, Dossett ML, Wolfl M et al (2007) Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 109:2331–2338
Voss RH, Willemsen RA, Kuball J et al (2008) Molecular design of the Calphabeta interface favors specific pairing of introduced TCRalphabeta in human T cells. J Immunol 180:391–401
Aggen DH, Chervin AS, Schmitt TM et al (2012) Single-chain ValphaVbeta T-cell receptors function without mispairing with endogenous TCR chains. Gene Ther 19:365–374
Sebestyen Z, Schooten E, Sals T et al (2008) Human TCR that incorporate CD3zeta induce highly preferred pairing between TCRalpha and beta chains following gene transfer. J Immunol 180:7736–7746
Saito T, Hochstenbach F, Marusic-Galesic S et al (1988) Surface expression of only gamma delta and/or alpha beta T cell receptor heterodimers by cells with four (alpha, beta, gamma, delta) functional receptor chains. J Exp Med 168:1003–1020
van der Veken LT, Coccoris M, Swart E et al (2009) Alpha beta T cell receptor transfer to gamma delta T cells generates functional effector cells without mixed TCR dimers in vivo. J Immunol 182:164–170
Okamoto S, Mineno J, Ikeda H et al (2009) Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res 69:9003–9011
Provasi E, Genovese P, Lombardo A et al (2012) Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat Med 18(5):807–815
Jorritsma A, Gomez-Eerland R, Dokter M et al (2007) Selecting highly affine and well-expressed TCRs for gene therapy of melanoma. Blood 110:3564–3572
Kuball J, Hauptrock B, Malina V et al (2009) Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain. J Exp Med 206:463–475
Haga-Friedman A, Horovitz-Fried M, Cohen CJ (2012) Incorporation of transmembrane hydrophobic mutations in the TCR enhance its surface expression and T cell functional avidity. J Immunol 188:5538–5546
Uckert W, Schumacher TN (2009) TCR transgenes and transgene cassettes for TCR gene therapy: status in 2008. Cancer Immunol Immunother 58:809–822
Merhavi-Shoham E, Haga-Friedman A, Cohen CJ (2012) Genetically modulating T-cell function to target cancer. Semin Cancer Biol 22:14–22
Brunda MJ, Luistro L, Warrier RR et al (1993) Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 178:1223–1230
Cavallo F, Di Carlo E, Butera M et al (1999) Immune events associated with the cure of established tumors and spontaneous metastases by local and systemic interleukin 12. Cancer Res 59:414–421
Zhang L, Kerkar SP, Yu Z et al (2011) Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment. Mol Ther 19:751–759
Krieg C, Letourneau S, Pantaleo G et al (2010) Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci USA 107:11906–11911
Berger C, Jensen MC, Lansdorp PM et al (2008) Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest 118:294–305
Hinrichs CS, Borman ZA, Cassard L et al (2009) Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci USA 106:17469–17474
Turtle CJ, Riddell SR (2011) Genetically retargeting CD8+ lymphocyte subsets for cancer immunotherapy. Curr Opin Immunol 23:299–305
Gorelik L, Constant S, Flavell RA (2002) Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. J Exp Med 195:1499–1505
Gorelik L, Flavell RA (2002) Transforming growth factor-beta in T-cell biology. Nat Rev Immunol 2:46–53
Knaus PI, Lindemann D, DeCoteau JF et al (1996) A dominant inhibitory mutant of the type II transforming growth factor beta receptor in the malignant progression of a cutaneous T-cell lymphoma. Mol Cell Biol 16:3480–3489
Park K, Kim SJ, Bang YJ et al (1994) Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. Proc Natl Acad Sci USA 91:8772–8776
Gorelik L, Flavell RA (2001) Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med 7:1118–1122
Zhang L, Yu Z, Muranski P et al (2013) Inhibition of TGF-beta signaling in genetically engineered tumor antigen-reactive T cells significantly enhances tumor treatment efficacy. Gene Ther 20(5):575–580
Bollard CM, Rossig C, Calonge MJ et al (2002) Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood 99:3179–3187
Foster AE, Dotti G, Lu A et al (2008) Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor. J Immunother 31:500–505
Chou CK, Schietinger A, Liggitt HD et al (2012) Cell-intrinsic abrogation of TGF-beta signaling delays but does not prevent dysfunction of self/tumor-specific CD8 T cells in a murine model of autochthonous prostate cancer. J Immunol 189:3936–3946
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
Moeller M, Haynes NM, Kershaw MH et al (2005) Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection. Blood 106:2995–3003
Cohen CJ, Denkberg G, Lev A et al (2003) Recombinant antibodies with MHC-restricted, peptide-specific, T-cell receptor-like specificity: new tools to study antigen presentation and TCR-peptide-MHC interactions. J Mol Recognit 16:324–332
Willemsen RA, Ronteltap C, Chames P et al (2005) T cell retargeting with MHC class I-restricted antibodies: the CD28 costimulatory domain enhances antigen-specific cytotoxicity and cytokine production. J Immunol 174:7853–7858
Niederman TM, Ghogawala Z, Carter BS et al (2002) Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors. Proc Natl Acad Sci USA 99:7009–7014
Muniappan A, Banapour B, Lebkowski J et al (2000) Ligand-mediated cytolysis of tumor cells: use of heregulin-zeta chimeras to redirect cytotoxic T lymphocytes. Cancer Gene Ther 7:128–134
Kahlon KS, Brown C, Cooper LJ et al (2004) Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells. Cancer Res 64:9160–9166
Zhang T, Wu MR, Sentman CL (2012) An NKp30-based chimeric antigen receptor promotes T cell effector functions and antitumor efficacy in vivo. J Immunol 189:2290–2299
Sentman CL, Barber MA, Barber A et al (2006) NK cell receptors as tools in cancer immunotherapy. Adv Cancer Res 95:249–292
Sadelain M, Brentjens R, Riviere I (2009) The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol 21:215–223
Guest RD, Hawkins RE, Kirillova N et al (2005) The role of extracellular spacer regions in the optimal design of chimeric immune receptors: evaluation of four different scFvs and antigens. J Immunother 28:203–211
Eshhar Z, Waks T, Gross G et al (1993) 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 USA 90:720–724
Holst J, Wang H, Eder KD et al (2008) Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity. Nat Immunol 9:658–666
Haynes NM, Snook MB, Trapani JA et al (2001) Redirecting mouse CTL against colon carcinoma: superior signaling efficacy of single-chain variable domain chimeras containing TCR-zeta vs Fc epsilon RI-gamma. J Immunol 166:182–187
Ren-Heidenreich L, Mordini R, Hayman GT et al (2002) Comparison of the TCR zeta-chain with the FcR gamma-chain in chimeric TCR constructs for T cell activation and apoptosis. Cancer Immunol Immunother 51:417–423
Gilham DE, O’Neil A, Hughes C et al (2002) Primary polyclonal human T lymphocytes targeted to carcino-embryonic antigens and neural cell adhesion molecule tumor antigens by CD3zeta-based chimeric immune receptors. J Immunother 25:139–151
Brocker T (2000) Chimeric Fv-zeta or Fv-epsilon receptors are not sufficient to induce activation or cytokine production in peripheral T cells. Blood 96:1999–2001
Felix NJ, Suri A, Salter-Cid L et al (2010) Targeting lymphocyte co-stimulation: from bench to bedside. Autoimmunity 43:514–525
Zang X, Allison JP (2007) The B7 family and cancer therapy: costimulation and coinhibition. Clin Cancer Res 13:5271–5279
Alvarez-Vallina L, Hawkins RE (1996) Antigen-specific targeting of CD28-mediated T cell co-stimulation using chimeric single-chain antibody variable fragment-CD28 receptors. Eur J Immunol 26:2304–2309
Kloss CC, Condomines M, Cartellieri M et al (2012) Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol 31:71–75
Maher J, Brentjens RJ, Gunset G et al (2002) Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol 20:70–75
Geiger TL, Nguyen P, Leitenberg D et al (2001) Integrated src kinase and costimulatory activity enhances signal transduction through single-chain chimeric receptors in T lymphocytes. Blood 98:2364–2371
Beecham EJ, Ma Q, Ripley R et al (2000) Coupling CD28 co-stimulation to immunoglobulin T-cell receptor molecules: the dynamics of T-cell proliferation and death. J Immunother 23:631–642
Hombach A, Wieczarkowiecz A, Marquardt T et al (2001) Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient IL-2 secretion and can be integrated into one combined CD28/CD3 zeta signaling receptor molecule. J Immunol 167:6123–6131
Spear P, Barber A, Rynda-Apple A et al (2012) Chimeric antigen receptor T cells shape myeloid cell function within the tumor microenvironment through IFN-gamma and GM-CSF. J Immunol 188:6389–6398
Loskog A, Giandomenico V, Rossig C et al (2006) Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. Leukemia 20:1819–1828
Koehler H, Kofler D, Hombach A et al (2007) CD28 costimulation overcomes transforming growth factor-beta-mediated repression of proliferation of redirected human CD4+ and CD8+ T cells in an antitumor cell attack. Cancer Res 67:2265–2273
Finney HM, Akbar AN, Lawson AD (2004) 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 172:104–113
Song DG, Ye Q, Poussin M et al (2012) CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood 119:696–706
Zhong XS, Matsushita M, Plotkin J et al (2010) Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell-mediated tumor eradication. Mol Ther 18:413–420
Wilkie S, Picco G, Foster J et al (2008) Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor. J Immunol 180:4901–4909
Pule MA, Straathof KC, Dotti G et al (2005) A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther 12:933–941
Gade TP, Hassen W, Santos E et al (2005) Targeted elimination of prostate cancer by genetically directed human T lymphocytes. Cancer Res 65:9080–9088
Haynes NM, Trapani JA, Teng MW et al (2002) Rejection of syngeneic colon carcinoma by CTLs expressing single-chain antibody receptors codelivering CD28 costimulation. J Immunol 169:5780–5786
Lamers CH, Sleijfer S, Vulto AG et al (2006) Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol 24:e20–e22
Kershaw MH, Westwood JA, Parker LL et al (2006) A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 12:6106–6115
Pule MA, Savoldo B, Myers GD et al (2008) Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med 14:1264–1270
Till BG, Jensen MC, Wang J 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
Kalos M, Levine BL, Porter DL 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
Till BG, Jensen MC, Wang J 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
Morgan RA, Yang JC, Kitano M et al (2010) Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 18:843–851
Brentjens R, Yeh R, Bernal Y et al (2010) Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial. Mol Ther 18:666–668
Torikai H, Reik A, Liu PQ 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
Feldman SA, Goff SL, Xu H et al (2011) Rapid production of clinical-grade gammaretroviral vectors in expanded surface roller bottles using a “modified” step-filtration process for clearance of packaging cells. Hum Gene Ther 22:107–115
Bear AS, Morgan RA, Cornetta K et al (2012) Replication-competent retroviruses in gene-modified T cells used in clinical trials: is it time to revise the testing requirements? Mol Ther 20:246–249
Costandi M (2013) Kite and NCI partner on T cells. Nat Biotechnol 31:10
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Shamalov, K., Tal, Y., Ankri, C., Cohen, C.J. (2014). Adoptive T-Cell Immunotherapy: Perfecting Self-Defenses. In: Klink, M. (eds) Interaction of Immune and Cancer Cells. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1300-4_9
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