Abstract
Adoptively transferred T cells have the capacity to traffic to distant tumor sites,
infiltrate fibrotic tissue and kill antigen-expressing tumor cells. Various groups
have investigated different genetic engineering strategies designed to enhance tumor
specificity, increase T cell potency, improve proliferation, persistence or migratory
capacity and increase safety. This review focuses on recent developments in T cell
engineering, discusses the clinical application of these engineered cell products
and outlines future prospects for this therapeutic modality.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to CytotherapyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen.Blood. 2009; 114: 535-546
- Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma.J Immunother. 2001; 24: 363-373
- Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes.Science. 2002; 298: 850-854
- Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes.Proc Natl Acad Sci U S A. 2004; 101: 14639-14645
- Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma.J Clin Oncol. 2005; 23: 2346-2357
- Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr virus-related lymphoproliferation.Lancet. 1995; 345: 9-13
- Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes.Nat Med. 1996; 2: 551-555
- Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients.Blood. 2010; 115: 925-935
- Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer.Blood. 2007; 110: 2838-2845
- The generation and characterization of LMP2-specific CTLs for use as adoptive transfer from patients with relapsed EBV-positive Hodgkin disease.J Immunother. 2004; 27: 317-327
- Cytotoxic T lymphocyte therapy for Epstein-Barr virus+ Hodgkin's disease.J Exp Med. 2004; 200: 1623-1633
- Characterization of latent membrane protein 2 specificity in CTL lines from patients with EBV-positive nasopharyngeal carcinoma and lymphoma.J Immunol. 2005; 175: 4137-4147
- Treatment of nasopharyngeal carcinoma with Epstein-Barr virus-specific T lymphocytes.Blood. 2005; 105: 1898-1904
- Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients.Blood. 2009; 113: 2442-2450
- Improving T cell therapy for cancer.Annu Rev Immunol. 2007; 25: 243-265
- Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells.Sci Transl Med. 2012; 1: 132ra53
- Replication-competent retroviruses in gene-modified T cells used in clinical trials: is it time to revise the testing requirements?.Mol Ther. 2012; 20: 246-249
- Redirecting specificity of T-cell populations for CD19 using the Sleeping Beauty system.Cancer Res. 2008; 68: 2961-2971
- Efficacy and safety of Sleeping Beauty transposon-mediated gene transfer in preclinical animal studies.Curr Gene Ther. 2011; 11: 341-349
- Translating Sleeping Beauty transposition into cellular therapies: victories and challenges.BioEssays. 2010; 32: 756-767
- Optimization of the PiggyBac transposon system for the sustained genetic modification of human T lymphocytes.J Immunother. 2009; 32: 826-836
- Transgenic mice with a diverse human T cell antigen receptor repertoire.Nat Med. 2010; 16: 1029-1034
- MHC-restricted fratricide of human lymphocytes expressing survivin-specific transgenic T cell receptors.J Clin Invest. 2010; 120: 3869-3877
- Monoclonal T-cell receptors: new reagents for cancer therapy.Mol Ther. 2007; 15: 1744-1750
- Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials.Clin Cancer Res. 2010; 16: 5852-5861
- Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond.Cancer Res. 2007; 67: 3898-3903
- T-cell receptor gene therapy: critical parameters for clinical success.J Invest Dermatol. 2011; 131: 1806-1816
- Prospects and limitations of T cell receptor gene therapy.Curr Gene Ther. 2011; 11: 276-287
- Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer.Nat Med. 2012; 18: 807-815
- 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: 5697-5705
- Rapid alphabeta TCR-mediated responses in gammadelta T cells transduced with cancer-specific TCR genes.Gene Ther. 2009; 16: 620-628
- Cancer regression in patients after transfer of genetically engineered lymphocytes.Science. 2006; 314: 126-129
- T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis.Mol Ther. 2011; 19: 620-626
- 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: 917-924
- Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy.J Immunother. 2013; 36: 133-151
- Thymic expression of the main immunogenic region of titin in thymomatous myasthenia gravis.J Int Med Res. 2010; 38: 1324-1332
- Cardiovascular toxicity and titin cross-reactivity of affinity enhanced T cells in myeloma and melanoma.Blood. 2013; 122: 863-871
- Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells.Sci Transl Med. 2013; 5: 197ra103
- Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy.Expert Opin Biol Ther. 2011; 11: 855-873
- CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients.J Clin Invest. 2011; 121: 1822-1826
- Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia.N Engl J Med. 2011; 365: 725-733
- 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
- Chimeric antigen receptor-modified T cells for acute lymphoid leukemia.N Engl J Med. 2013; 368: 1509-1518
- Safer CARS.Mol Ther. 2010; 18: 661-662
- Do CARs need a driver's license? Adoptive cell therapy with chimeric antigen receptor-redirected T cells has caused serious adverse events.Hum Gene Ther. 2010; 21: 1039-1042
- Chimeric T cells for adoptive immunotherapy of cancer: using what have we learned to plan for the future.Immunotherapy. 2009; 1: 905-912
- Immune responses to transgene and retroviral vector in patients treated with ex vivo-engineered T cells.Blood. 2011; 117: 72-82
- Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo.Cancer Immunol Immunother. 2007; 56: 1875-1883
- 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-e22
- A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer.Clin Cancer Res. 2006; 12: 6106-6115
- 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. 2010; 16: 1245-1256
- Unexpected toxicity of cyclophosphamide followed by adoptively transferred CD19-targeted T cells in a patient with bulky CLL.Mol Ther. 2009; 17: S157
- 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: 843-851
- Trafficking of CAR-engineered human T cells following regional or systemic adoptive transfer in SCID beige mice.J Clin Immunol. 2011; 31: 710-718
- Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling.J Clin Immunol. 2012; 32: 1059-1070
- Combinatorial antigen recognition with balanced signallung promotes selective tumor eradication by engineered T cells.Nat Biotech. 2013; 31: 71-75
- Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation.Mol Immunol. 2007; 45: 1276-1287
- Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4.J Biol Chem. 2010; 285: 25538-25544
- Combining T-cell immunotherapy and anti-androgen therapy for prostate cancer.Prostate Cancer Prostatic Dis. 2013; 16: 123-131
- 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: 6392-6402
- Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor.Clin Cancer Res. 2011; 17: 4719-4730
- Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b.J Immunother. 2010; 33: 780-788
- IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients.Blood. 2006; 107: 2409-2414
- Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes.Blood. 2007; 110: 2793-2802
- Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety.Leukemia. 2010; 24: 1160-1170
- Genetic manipulation of tumor-specific cytotoxic T lymphocytes to restore responsiveness to IL-7.Mol Ther. 2009; 17: 880-888
- IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells.J Immunother. 2006; 29: 313-319
- Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets.J Exp Med. 2008; 205: 1701-1714
- Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy.Clin Cancer Res. 2010; 16: 727-735
- Recombinant human interleukin-7 (CYT107) promotes T cell recovery following allogeneic stem cell transplantation.Blood. 2012; 120: 4882-4891
- A human memory T cell subset with stem cell-like properties.Nat Med. 2011; 17: 1290-1297
- Proliferation and differentiation potential of human CD8+ memory T-cell subsets in response to antigen or homeostatic cytokines.Blood. 2003; 101: 4260-4266
- Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function.J Exp Med. 2005; 201: 139-148
- 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
- The stoichiometric production of IL-2 and IFN-gamma mRNA defines memory T cells that can self-renew after adoptive transfer in humans.Sci Transl Med. 2012; 4: 149ra120
- Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma.Nat Med. 2008; 14: 1264-1270
- Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma.Blood. 2011; 118: 6050-6056
- Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells.Blood. 2012; 119: 72-82
- T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection.Nat Med. 2007; 13: 1440-1449
- Genetic manipulation of telomerase in HIV-specific CD8+ T cells: enhanced antiviral functions accompany the increased proliferative potential and telomere length stabilization.J Immunol. 2004; 173: 6303-6311
- Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase.J Immunol. 2000; 165: 4239-4245
- Ectopic human telomerase catalytic subunit expression maintains telomere length but is not sufficient for CD8+ T lymphocyte immortalization.J Immunol. 2000; 165: 4978-4984
- Bcl-2 overexpression enhances tumor-specific T-cell survival.Cancer Res. 2005; 65: 2001-2008
- Retroviral transduction of human peripheral blood lymphocytes with Bcl-X(L) promotes in vitro lymphocyte survival in pro-apoptotic conditions.Gene Ther. 2002; 9: 527-535
- Human cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosis.Blood. 2005; 105: 4677-4684
- Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity.Blood. 2002; 99: 3179-3187
- Assessing the safety of cytotoxic T lymphocytes transduced with a dominant negative transforming growth factor-beta receptor.J Immunother. 2006; 29: 250-260
- Antitumor activity of EBV-specific T lymphocytes transduced with a dominant negative TGF-beta receptor.J Immunother. 2008; 31: 500-505
- 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: 611-620
- Characterization of CD20-transduced T lymphocytes as an alternative suicide gene therapy approach for the treatment of graft-versus-host disease.Hum Gene Ther. 2004; 15: 63-76
- Abrogation of GvHD and early immune reconstitution after infusion of HSV-TK engineered donor lymphocytes after haplo-identical hematopoietic stem cell transplantation.Blood. 2002; 100: 115a
- The suicide gene therapy challenge: how to improve a successful gene therapy approach.Mol Ther. 2007; 15: 1248-1252
- Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation.Blood. 2007; 109: 4698-4707
- 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
- The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies.Blood. 2007; 109: 4708-4715
- Comparison of different suicide-gene strategies for the safety improvement of genetically manipulated T cells.Hum Gene Ther Methods. 2012; 23: 376-386
- An inducible caspase 9 safety switch for T-cell therapy.Blood. 2005; 105: 4247-4254
- An inducible caspase 9 suicide gene to improve the safety of mesenchymal stromal cell therapies.Stem Cells. 2010; 28: 1107-1115
- Inducible apoptosis as a safety switch for adoptive cell therapy.N Engl J Med. 2011; 365: 1673-1683
- Redirecting gene-modified T cells toward various cancer types using tagged antibodies.Clin Cancer Res. 2012; 18: 6436-6445
- Development of a novel universal immune receptor for antigen targeting: to Infinity and beyond.Oncoimmunology. 2012; 1: 777-779
- A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor.Cancer Res. 2012; 72: 1844-1852
- Culture of human T cells in stirred bioreactors for cellular immunotherapy applications: shear, proliferation, and the IL-2 receptor.Biotechnol Bioeng. 2000; 68: 328-338
- GMP production and testing of Xcellerated T Cells for the treatment of patients with CLL.Cytotherapy. 2004; 6: 554-562
- Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy.J Immunol Methods. 2009; 345: 90-99
- Large-scale bioreactor expansion of tumor-infiltrating lymphocytes.J Immunol Methods. 2011; 364: 94-100
- Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy in the WAVE bioreactor.J Transl Med. 2012; 10: 69
- Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy.J Immunother. 2009; 32: 169-180
- Accelerated production of antigen-specific T cells for preclinical and clinical applications using gas-permeable rapid expansion cultureware (G-Rex).J Immunother. 2010; 33: 305-315
- Optimization manufacture of virus- and tumor-specific T cells.Stem Cells Int. 2011; 2011: 434392
- Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications.Cytotherapy. 2012; 14: 1131-1143
- Simplified method of the growth of human tumor infiltrating lymphocytes in gas-permeable flasks to numbers needed for patient treatment.J Immunother. 2012; 35: 283-292
- T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect.Blood. 2003; 101: 1637-1644
- Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies.Blood Cells Mol Dis. 2004; 33: 83-89
- Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy.Cancer Res. 2007; 67: 2872-2880
- CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells.Cancer Res. 2006; 66: 10995-11004
- Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells.Leukemia. 2006; 20: 1819-1828
- Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo.Mol Ther. 2009; 17: 1453-1464
- 4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood T cells against B-cell malignancies.Hum Gene Ther. 2010; 21: 75-86
- Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15.Nat Med. 2003; 9: 279-286
- Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts.Clin Cancer Res. 2007; 13: 5426-5435
- Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor.J Immunother. 2009; 32: 689-702
- 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: 4099-4102
- 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: 2709-2720
- Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies.Hum Gene Ther. 2012; 23: 444-450
- 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. 2010; 18: 666-668
- Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias.Blood. 2011; 118: 4817-4828
- CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia.Sci Transl Med. 2013; 5: 177ra38
- Antibody-mediated B-cell depletion before adoptive immunotherapy with T cells expressing CD20-specific chimeric T-cell receptors facilitates eradication of leukemia in immunocompetent mice.Blood. 2009; 114: 5454-5463
- CD20 is a molecular target for scFvFc:zeta receptor redirected T cells: implications for cellular immunotherapy of CD20+ malignancy.Biol Blood Marrow Transplant. 1998; 4: 75-83
- Engineered CD20-specific primary human cytotoxic T lymphocytes for targeting B-cell malignancy.Cytotherapy. 2003; 5: 131-138
- Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells.Blood. 2008; 112: 2261-2271
- Cellular immunotherapy for follicular lymphoma using genetically modified CD20-specific CD8+ cytotoxic T lymphocytes.Mol Ther. 2004; 9: 577-586
- Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains.Hum Gene Ther. 2007; 18: 712-725
- CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results.Blood. 2012; 119: 3940-3950
- Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia.Blood. 2013; 121: 1165-1174
- An anti-CD30 chimeric receptor that mediates CD3-zeta-independent T-cell activation against Hodgkin's lymphoma cells in the presence of soluble CD30.Cancer Res. 1998; 58: 1116-1119
- Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease.Blood. 2007; 110: 2620-2630
- T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells.Blood. 2006; 108: 3890-3897
- T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies.Blood. 2011; 117: 4304-4314
- Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor.Br J Haematol. 2013; 161: 389-401
- Chimeric NKG2D receptor-expressing T cells as an immunotherapy for multiple myeloma.Exp Hematol. 2008; 36: 1318-1328
- Treatment of multiple myeloma with adoptively transferred chimeric NKG2D receptor-expressing T cells.Gene Ther. 2011; 18: 509-516
- Chimeric antigen receptor T cells shape myeloid cell function within the tumor microenvironment through IFN-gamma and GM-CSF.J Immunol. 2012; 188: 6389-6398
- NKG2D CAR T-cell therapy inhibits the growth of NKG2D ligand heterogeneous tumors.Immunol Cell Biol. 2013; 91: 435-440
- Targeting of G(D2)-positive tumor cells by human T lymphocytes engineered to express chimeric T-cell receptor genes.Int J Cancer. 2001; 94: 228-236
- Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy.Blood. 2002; 99: 2009-2016
- Targeting of T lymphocytes to Neu/HER2-expressing cells using chimeric single chain Fv receptors.J Immunol. 1993; 151: 6577-6582
- Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes.J Clin Invest. 2004; 114: 1774-1781
- Full-length dominant-negative survivin for cancer immunotherapy.Clin Cancer Res. 2003; 9: 6523-6533
- Regression of experimental medulloblastoma following transfer of HER2-specific T cells.Cancer Res. 2007; 67: 5957-5964
- 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: 5563-5574
- Transfer of Her-2/neu specificity into cytokine-induced killer (CIK) cells with RNA encoding chimeric immune receptor (CIR).J Clin Immunol. 2009; 29: 806-814
- Adoptive immunotherapy using human peripheral blood lymphocytes transferred with RNA encoding Her-2/neu-specific chimeric immune receptor in ovarian cancer xenograft model.Cancer Gene Ther. 2009; 16: 489-497
- Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression.Mol Ther. 2009; 17: 1779-1787
- Transfer of mRNA encoding recombinant immunoreceptors reprograms CD4+ and CD8+ T cells for use in the adoptive immunotherapy of cancer.Gene Ther. 2009; 16: 596-604
- Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain.J Exp Med. 1993; 178: 361-366
- In vivo antitumor activity of T cells redirected with chimeric antibody/T-cell receptor genes.Cancer Res. 1995; 55: 3369-3373
- Dual-specific T cells combine proliferation and antitumor activity.Nat Biotechnol. 2002; 20: 1221-1227
- Expansion and characterization of T cells transduced with a chimeric receptor against ovarian cancer.Hum Gene Ther. 2000; 11: 2377-2387
- Genetic engineering of cytolytic T lymphocytes for adoptive T-cell therapy of neuroblastoma.J Gene Med. 2004; 6: 704-711
- Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma.Mol Ther. 2007; 15: 825-833
- Chimeric scFv/gamma receptor-mediated T-cell lysis of tumor cells is coregulated by adhesion and accessory molecules.Int J Cancer. 1998; 77: 181-187
- A retroviral vector system ‘STITCH' in combination with an optimized single chain antibody chimeric receptor gene structure allows efficient gene transduction and expression in human T lymphocytes.Gene Ther. 1998; 5: 1195-1203
- Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity.Mol Ther. 2013; 21: 904-912
- 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: 123-127
- Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor.Nat Biotechnol. 2002; 20: 70-75
- 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: 2199-2209
- Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells.Cancer Res. 2004; 64: 9160-9166
- Medulloblastomas expressing IL13Ralpha2 are targets for IL13-zetakine+ cytolytic T cells.J Pediatr Hematol Oncol. 2007; 29: 669-677
- Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells.Clin Cancer Res. 2012; 18: 5949-5960
- T cells redirected to EphA2 for the immunotherapy of glioblastoma.Mol Ther. 2012; 21: 629-637
- Antitumor effects of chimeric receptor engineered human T cells directed to tumor stroma.Mol Ther. 2013; 21: 1611-1620
- Generation of gene-modified T cells reactive against the angiogenic kinase insert domain-containing receptor (KDR) found on tumor vasculature.Hum Gene Ther. 2000; 11: 2445-2452
- Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors.Proc Natl Acad Sci U S A. 2002; 99: 7009-7014
- Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice.J Clin Invest. 2010; 120: 3953-3968
- 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: 3371-3380
- Specificity redirection by CAR with human VEGFR-1 affinity endows T lymphocytes with tumor-killing ability and anti-angiogenic potency.Gene Ther. 2013; 20: 970-978
- Retrovirally engineered T-cell-based immunotherapy targeting type III variant epidermal growth factor receptor, a glioma-associated antigen.Cancer Sci. 2010; 101: 2518-2524
- 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: 1043-1053
- Cellular immunotherapy for carcinoma using genetically modified EGFR-specific T lymphocytes.Neoplasia. 2013; 15: 544-553
- Chimeric antigen receptor containing ICOS signaling domain mediates specific and efficient antitumor effect of T cells against EGFRvIII expressing glioma.J Hematol Oncol. 2013; 6: 33
- 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: 3360-3365
- Redirected antitumor activity of primary human lymphocytes transduced with a fully human anti-mesothelin chimeric receptor.Mol Ther. 2012; 20: 633-643
- Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.Cancer Res. 2010; 70: 9053-9061
- Growth retardation of tumors by adoptive transfer of cytotoxic T lymphocytes reprogrammed by CD44v6-specific scFv:zeta-chimera.Int J Cancer. 1996; 68: 232-238
- In vivo cervical cancer growth inhibition by genetically engineered cytotoxic T cells.Cancer Immunol Immunother. 2005; 54: 51-60
- T cell targeting of TAG72+ tumor cells by a chimeric receptor with antibody-like specificity for a carbohydrate epitope.Gastroenterology. 1997; 113: 1163-1170
- Anti-tumor activity of human T cells expressing the CC49-zeta chimeric immune receptor.Hum Gene Ther. 1999; 10: 165-173
- Transfer of chimeric receptor gene made of variable regions of tumor-specific antibody confers anticarbohydrate specificity on T cells.Cancer Gene Ther. 1998; 5: 401-407
- Gene-modified T cells as immunotherapy for multiple myeloma and acute myeloid leukemia expressing the Lewis Y antigen.Gene Ther. 2010; 17: 678-686
- Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of Lewis-Y-expressing tumors in mice.Proc Natl Acad Sci U S A. 2005; 102: 19051-19056
- The Lewis-Y carbohydrate antigen is expressed by many human tumors and can serve as a target for genetically redirected T cells despite the presence of soluble antigen in serum.J Immunother. 2009; 32: 292-301
- Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor.J Immunol. 2008; 180: 4901-4909
- Rhabdomyosarcoma lysis by T cells expressing a human autoantibody-based chimeric receptor targeting the fetal acetylcholine receptor.Cancer Res. 2006; 66: 24-28
- Targeting the fetal acetylcholine receptor in rhabdomyosarcoma.Expert Opin Ther Targets. 2013; 17: 127-138
- 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. 2002; 25: 139-151
- Gene therapy of patient-derived T lymphocytes to target and eradicate colorectal hepatic metastases.Dis Colon Rectum. 2003; 46: 793-804
- 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: 6938-6949
- Expression in cytotoxic T lymphocytes of a single-chain anti-carcinoembryonic antigen antibody: redirected Fas ligand-mediated lysis of colon carcinoma.Eur J Immunol. 1998; 28: 1663-1672
- Bypassing immunization: optimized design of “designer T cells” against carcinoembryonic antigen (CEA)-expressing tumors, and lack of suppression by soluble CEA.Clin Cancer Res. 1999; 5: 3928-3941
- 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. 2001; 167: 6123-6131
- Rejection of syngeneic colon carcinoma by CTLs expressing single-chain antibody receptors codelivering CD28 costimulation.J Immunol. 2002; 169: 5780-5786
- Carcinoembryonic antigen-immunoglobulin Fc fusion protein (CEA-Fc) for identification and activation of anti-CEA immunoglobulin-T-cell receptor-modified T cells, representative of a new class of Ig fusion proteins.Cancer Gene Ther. 2004; 11: 297-306
- Second-generation anti-carcinoembryonic antigen designer T cells resist activation-induced cell death, proliferate on tumor contact, secrete cytokines, and exhibit superior antitumor activity in vivo: a preclinical evaluation.Clin Cancer Res. 2008; 14: 8112-8122
- Construction and molecular characterization of human chimeric T-cell antigen receptors specific for carcinoembryonic antigen.Anticancer Res. 2010; 30: 2731-2738
- T cells redirected by a CD3zeta chimeric antigen receptor can establish self-antigen-specific tumour protection in the long term.Gene Ther. 2013; 20: 177-186
- Generation and targeting of human tumor-specific Tc1 and Th1 cells transduced with a lentivirus containing a chimeric immunoglobulin T-cell receptor.Cancer Res. 2004; 64: 1490-1495
- Antitumor activity of chimeric immunoreceptor gene-modified Tc1 and Th1 cells against autologous carcinoembryonic antigen-expressing colon cancer cells.Cancer Sci. 2006; 97: 920-927
- A fully human chimeric immune receptor for retargeting T-cells to CEA-expressing tumor cells.Anticancer Res. 2006; 26: 4067-4072
- T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice.Gastroenterology. 2012; 143: 1095-1107
- Specific targeting of EGP-2+ tumor cells by primary lymphocytes modified with chimeric T cell receptors.Hum Gene Ther. 2000; 11: 9-19
- Comparison of the TCR zeta-chain with the FcR gamma-chain in chimeric TCR constructs for T cell activation and apoptosis.Cancer Immunol Immunother. 2002; 51: 417-423
- Recognition of human colon cancer by T cells transduced with a chimeric receptor gene.Cancer Gene Ther. 2000; 7: 284-291
- Cytolysis of tumor cells expressing the Neu/erbB-2, erbB-3, and erbB-4 receptors by genetically targeted naive T lymphocytes.Clin Cancer Res. 1996; 2: 1001-1008
- Ligand-mediated cytolysis of tumor cells: use of heregulin-zeta chimeras to redirect cytotoxic T lymphocytes.Cancer Gene Ther. 2000; 7: 128-134
- Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells.Mol Med. 2012; 18: 565-576
- Anti-GD3 chimeric sFv-CD28/T-cell receptor zeta designer T cells for treatment of metastatic melanoma and other neuroectodermal tumors.Clin Cancer Res. 2010; 16: 2769-2780
- Targeting of T lymphocytes to melanoma cells through chimeric anti-GD3 immunoglobulin T-cell receptors.Neoplasia. 2000; 2: 449-459
- Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells.Prostate. 2007; 67: 1121-1131
- Engineered T cells for pancreatic cancer treatment.HPB (Oxford). 2011; 13: 643-650
- Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells.Nat Biotechnol. 2013; 31: 71-75
- Grafting primary human T lymphocytes with cancer-specific chimeric single chain and two chain TCR.Gene Ther. 2000; 7: 1369-1377
- A phage display selected fab fragment with MHC class I-restricted specificity for MAGE-A1 allows for retargeting of primary human T lymphocytes.Gene Ther. 2001; 8: 1601-1608
- T cell retargeting with MHC class I-restricted antibodies: the CD28 costimulatory domain enhances antigen-specific cytotoxicity and cytokine production.J Immunol. 2005; 174: 7853-7858
- Immunotherapy with chimeric NKG2D receptors leads to long-term tumor-free survival and development of host antitumor immunity in murine ovarian cancer.J Immunol. 2008; 180: 72-78
- Chimeric NKG2D expressing T cells eliminate immunosuppression and activate immunity within the ovarian tumor microenvironment.J Immunol. 2009; 183: 6939-6947
- Chimeric NK-receptor-bearing T cells mediate antitumor immunotherapy.Blood. 2005; 106: 1544-1551
- Chimeric NKG2D modified T cells inhibit systemic T-cell lymphoma growth in a manner involving multiple cytokines and cytotoxic pathways.Cancer Res. 2007; 67: 11029-11036
- Mouse tumor vasculature expresses NKG2D ligands and can be targeted by chimeric NKG2D-modified T cells.J Immunol. 2013; 190: 2455-2463
- Chimeric NKG2D receptor-bearing T cells as immunotherapy for ovarian cancer.Cancer Res. 2007; 67: 5003-5008
- Generation of antitumor responses by genetic modification of primary human T cells with a chimeric NKG2D receptor.Cancer Res. 2006; 66: 5927-5933
- Redirecting T cells to Ewing's sarcoma family of tumors by a chimeric NKG2D receptor expressed by lentiviral transduction or mRNA transfection.PLoS One. 2012; 7: e31210
Article info
Publication history
Published online: November 18, 2013
Accepted:
October 5,
2013
Received:
July 22,
2013
Identification
Copyright
© 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
