Home LiteratureArticle Details
PMID: 20439624 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor.

Blood ·Vol. 116 ·No. 7 ·2010-08-19 ·Pages 1035-44

Jena B, Dotti G, Cooper LJ

Abstract

Infusions of antigen-specific T cells have yielded therapeutic responses in patients with pathogens and tumors. To broaden the clinical application of adoptive immunotherapy against malignancies, investigators have developed robust systems for the genetic modification and characterization of T cells expressing introduced chimeric antigen receptors (CARs) to redirect specificity. Human trials are under way in patients with aggressive malignancies to test the hypothesis that manipulating the recipient and reprogramming T cells before adoptive transfer may improve their therapeutic effect. These examples of personalized medicine infuse T cells designed to meet patients' needs by redirecting their specificity to target molecular determinants on the underlying malignancy. The generation of clinical grade CAR(+) T cells is an example of bench-to-bedside translational science that has been accomplished using investigator-initiated trials operating largely without industry support. The next-generation trials will deliver designer T cells with improved homing, CAR-mediated signaling, and replicative potential, as investigators move from the bedside to the bench and back again.

MeSH Terms
Animals Antigens, Neoplasm/immunology Humans Immunotherapy Neoplasms/immunology Receptors, Antigen, T-Cell/genetics,metabolism Recombinant Fusion Proteins/therapeutic use T-Lymphocytes/immunology
Chemicals
Antigens, Neoplasm Receptors, Antigen, T-Cell Recombinant Fusion Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Jena Bipulendu
Division of Pediatrics, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Dotti Gianpietro
Cooper Laurence J N
References (164)
164 references, click to expand
  1. Expression of a CD20-specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of lymphoma and leukemia cells.
    Cancer Immunol Immunother. 2008 Mar;57(3):411-23 PMID: 17717662
  2. Dual-specific T cells combine proliferation and antitumor activity.
    Nat Biotechnol. 2002 Dec;20(12):1221-7 PMID: 12415288
  3. Selective accumulation of virus-specific CD8+ T cells with unique homing phenotype within the human bone marrow.
    Blood. 2008 Oct 15;112(8):3293-302 PMID: 18635810
  4. T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8905-9 PMID: 1833767
  5. Rejection of syngeneic colon carcinoma by CTLs expressing single-chain antibody receptors codelivering CD28 costimulation.
    J Immunol. 2002 Nov 15;169(10):5780-6 PMID: 12421958
  6. Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2.
    Hum Gene Ther. 2002 Nov 1;13(16):1971-80 PMID: 12427307
  7. Treatment of lymphoma with adoptively transferred T cells.
    Expert Opin Biol Ther. 2009 Nov;9(11):1407-25 PMID: 19723016
  8. A functional role for CD28 costimulation in tumor recognition by single-chain receptor-modified T cells.
    Cancer Gene Ther. 2004 May;11(5):371-9 PMID: 15060573
  9. Targeting of tumor cells by lymphocytes engineered to express chimeric receptor genes.
    Cancer Immunol Immunother. 2004 Oct;53(10):893-903 PMID: 15168086
  10. Targeting of T lymphocytes to melanoma cells through chimeric anti-GD3 immunoglobulin T-cell receptors.
    Neoplasia. 2000 Sep-Oct;2(5):449-59 PMID: 11191112
  11. T cell activation by antibody-like immunoreceptors: increase in affinity of the single-chain fragment domain above threshold does not increase T cell activation against antigen-positive target cells but decreases selectivity.
    J Immunol. 2004 Dec 15;173(12):7647-53 PMID: 15585893
  12. Chimeric NK-receptor-bearing T cells mediate antitumor immunotherapy.
    Blood. 2005 Sep 1;106(5):1544-51 PMID: 15890688
  13. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1.
    J Clin Invest. 2008 Sep;118(9):3132-42 PMID: 18688285
  14. Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors.
    Nat Biotechnol. 2008 Apr;26(4):453-61 PMID: 18376399
  15. Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor.
    J Immunother. 2009 Sep;32(7):689-702 PMID: 19561539
  16. Functional human antigen-specific T cells produced in vitro using retroviral T cell receptor transfer into hematopoietic progenitors.
    J Immunol. 2007 Oct 15;179(8):4959-68 PMID: 17911580
  17. 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 Nov 15;66(22):10995-1004 PMID: 17108138
  18. Derivation of human T lymphocytes from cord blood and peripheral blood with antiviral and antileukemic specificity from a single culture as protection against infection and relapse after stem cell transplantation.
    Blood. 2010 Apr 1;115(13):2695-703 PMID: 20110422
  19. T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection.
    Nat Med. 2007 Dec;13(12):1440-9 PMID: 18026115
  20. Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells.
    Cancer Res. 2004 Dec 15;64(24):9160-6 PMID: 15604287
  21. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes.
    Science. 2002 Oct 25;298(5594):850-4 PMID: 12242449
  22. Engineered human tmpk/AZT as a novel enzyme/prodrug axis for suicide gene therapy.
    Mol Ther. 2007 May;15(5):962-70 PMID: 17375075
  23. Novel strategies for cancer therapy: the potential of genetically modified T lymphocytes.
    Curr Hematol Rep. 2004 Jul;3(4):290-7 PMID: 15217559
  24. Persuading natural killer cells to eliminate bad B cells.
    Clin Cancer Res. 2009 Aug 1;15(15):4790-1 PMID: 19638468
  25. Genetic modification of human T cells with CD20: a strategy to purify and lyse transduced cells with anti-CD20 antibodies.
    Hum Gene Ther. 2000 Mar 1;11(4):611-20 PMID: 10724039
  26. Zoledronate facilitates large-scale ex vivo expansion of functional gammadelta T cells from cancer patients for use in adoptive immunotherapy.
    Cytotherapy. 2008;10(8):842-56 PMID: 19016372
  27. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets.
    J Exp Med. 2008 Jul 7;205(7):1701-14 PMID: 18573906
  28. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma.
    Nat Med. 2008 Nov;14(11):1264-70 PMID: 18978797
  29. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo.
    Mol Ther. 2009 Aug;17(8):1453-64 PMID: 19384291
  30. Loss of mismatched HLA in leukemia after stem-cell transplantation.
    N Engl J Med. 2009 Jul 30;361(5):478-88 PMID: 19641204
  31. Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy.
    Blood. 2002 Mar 15;99(6):2009-16 PMID: 11877273
  32. Manufacturing of gene-modified cytotoxic T lymphocytes for autologous cellular therapy for lymphoma.
    Cytotherapy. 2006;8(2):105-17 PMID: 16698684
  33. Transgene expression levels determine the immunogenicity of transduced hematopoietic grafts in partially myeloablated mice.
    Mol Ther. 2009 Nov;17(11):1904-9 PMID: 19707185
  34. Immune response manipulation: recombinant immunoreceptors endow T-cells with predefined specificity.
    Curr Pharm Des. 2003;9(24):1992-2001 PMID: 12871185
  35. The promise and potential pitfalls of chimeric antigen receptors.
    Curr Opin Immunol. 2009 Apr;21(2):215-23 PMID: 19327974
  36. Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy.
    Haematologica. 2009 Sep;94(9):1316-20 PMID: 19734426
  37. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15.
    Nat Med. 2003 Mar;9(3):279-86 PMID: 12579196
  38. Genetic modification of T lymphocytes for adoptive immunotherapy.
    Mol Ther. 2004 Jul;10(1):5-18 PMID: 15233937
  39. Risk in clinical research: size matters!
    Mol Ther. 2009 Nov;17(11):1833-4 PMID: 19876046
  40. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety.
    Leukemia. 2010 Jun;24(6):1160-70 PMID: 20428207
  41. Sleeping Beauty transposon system--future trend in T-cell-based gene therapies?
    Future Oncol. 2006 Jun;2(3):345-9 PMID: 16787113
  42. Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect.
    Blood. 2002 Sep 15;100(6):1935-47 PMID: 12200350
  43. Genetic redirection of T cells for cancer therapy.
    J Leukoc Biol. 2010 May;87(5):791-803 PMID: 20179152
  44. Sleeping beauty vector system moves toward human trials in the United States.
    Mol Ther. 2008 Sep;16(9):1515-6 PMID: 18725873
  45. Harnessing endogenous miR-181a to segregate transgenic antigen receptor expression in developing versus post-thymic T cells in murine hematopoietic chimeras.
    J Clin Invest. 2009 Jan;119(1):157-68 PMID: 19033646
  46. The T-body approach: redirecting T cells with antibody specificity.
    Handb Exp Pharmacol. 2008;(181):329-42 PMID: 18071952
  47. Genetic engineering of T cells for adoptive immunotherapy.
    Immunol Res. 2008;42(1-3):166-81 PMID: 18841331
  48. Selective expansion of genetically modified T cells using an antibody/interleukin-2 receptor chimera.
    J Immunol Methods. 2008 Aug 20;337(1):16-23 PMID: 18589435
  49. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells.
    Blood. 2008 Sep 15;112(6):2261-71 PMID: 18509084
  50. Adoptive cell therapy for patients with melanoma, using tumor-infiltrating lymphocytes genetically engineered to secrete interleukin-2.
    Hum Gene Ther. 2008 May;19(5):496-510 PMID: 18444786
  51. 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 Sep;16(9):1245-56 PMID: 20304086
  52. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):10024-8 PMID: 2513569
  53. 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 Nov;8(21):1601-8 PMID: 11894998
  54. Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor-specific cytotoxic T lymphocytes.
    Blood. 2007 Oct 15;110(8):2793-802 PMID: 17638856
  55. 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 Feb 15;64(4):1490-5 PMID: 14973062
  56. Highly efficient redirected anti-tumor activity of human lymphocytes transduced with a completely human chimeric immune receptor.
    J Gene Med. 2005 Feb;7(2):158-70 PMID: 15538730
  57. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2.
    Mol Ther. 2010 Apr;18(4):843-51 PMID: 20179677
  58. Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells.
    J Immunother. 2010 Jan;33(1):1-7 PMID: 19952961
  59. Fifteen years of gene therapy based on chimeric antigen receptors: "are we nearly there yet?".
    Hum Gene Ther. 2009 Nov;20(11):1229-39 PMID: 19702437
  60. A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity.
    J Immunol. 2009 Nov 1;183(9):5563-74 PMID: 19843940
  61. Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells.
    Cell. 1997 Nov 14;91(4):501-10 PMID: 9390559
  62. T-cell genetic modification for re-directed tumor recognition.
    Cancer Chemother Biol Response Modif. 2005;22:293-324 PMID: 16110618
  63. Human gammadelta T cells as mediators of chimaeric-receptor redirected anti-tumour immunity.
    Br J Haematol. 2004 Aug;126(4):583-92 PMID: 15287953
  64. Safer CARS.
    Mol Ther. 2010 Apr;18(4):661-2 PMID: 20357776
  65. Human T lymphocyte genetic modification with naked DNA.
    Mol Ther. 2000 Jan;1(1):49-55 PMID: 10933911
  66. Engineering lymphocyte subsets: tools, trials and tribulations.
    Nat Rev Immunol. 2009 Oct;9(10):704-16 PMID: 19859065
  67. 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 Jun 1;109(11):4708-15 PMID: 17327417
  68. T-cell killing of heterogenous tumor or viral targets with bispecific chimeric immune receptors.
    Cancer Gene Ther. 2000 Aug;7(8):1127-34 PMID: 10975673
  69. An inducible caspase 9 safety switch for T-cell therapy.
    Blood. 2005 Jun 1;105(11):4247-54 PMID: 15728125
  70. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants.
    Science. 2002 Mar 15;295(5562):2097-100 PMID: 11896281
  71. Non-redundant role for IL-7R signaling for the survival of CD8+ memory T cells.
    Eur J Immunol. 2007 Nov;37(11):3078-88 PMID: 17935075
  72. Supernatural T cells: genetic modification of T cells for cancer therapy.
    Nat Rev Immunol. 2005 Dec;5(12):928-40 PMID: 16322746
  73. Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells.
    Leukemia. 2006 Oct;20(10):1819-28 PMID: 16932339
  74. A panel of artificial APCs expressing prevalent HLA alleles permits generation of cytotoxic T cells specific for both dominant and subdominant viral epitopes for adoptive therapy.
    J Immunol. 2009 Aug 15;183(4):2837-50 PMID: 19635907
  75. PET imaging of T cells derived from umbilical cord blood.
    Leukemia. 2009 Mar;23(3):620-2 PMID: 18830258
  76. 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 May-Jun;29(3):313-9 PMID: 16699374
  77. Improving T cell therapy for cancer.
    Expert Opin Biol Ther. 2006 Mar;6(3):215-29 PMID: 16503732
  78. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals.
    Nat Med. 2006 Oct;12(10):1160-6 PMID: 16998485
  79. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease.
    Blood. 2001 Mar 1;97(5):1249-57 PMID: 11222367
  80. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector.
    Science. 1996 Apr 12;272(5259):263-7 PMID: 8602510
  81. Immunotherapy of metastatic melanoma using genetically engineered GD2-specific T cells.
    Clin Cancer Res. 2009 Sep 15;15(18):5852-60 PMID: 19737958
  82. Stable gene transfer and expression in cord blood-derived CD34+ hematopoietic stem and progenitor cells by a hyperactive Sleeping Beauty transposon system.
    Blood. 2009 Aug 13;114(7):1319-30 PMID: 19414858
  83. 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 Jan 1;172(1):104-13 PMID: 14688315
  84. Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity.
    Blood. 2002 May 1;99(9):3179-87 PMID: 11964281
  85. Adoptive T cell therapy of cancer.
    Curr Opin Immunol. 2010 Apr;22(2):251-7 PMID: 20171074
  86. Recognition and killing of brain tumor stem-like initiating cells by CD8+ cytolytic T cells.
    Cancer Res. 2009 Dec 1;69(23):8886-93 PMID: 19903840
  87. Genetic engineering of T cell specificity for immunotherapy of cancer.
    Hum Immunol. 2003 Jan;64(1):56-68 PMID: 12507815
  88. 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 Dec 10;99(25):16168-73 PMID: 12427970
  89. Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules.
    Mol Ther. 2007 May;15(5):981-8 PMID: 17375070
  90. Genetic manipulation of tumor-specific cytotoxic T lymphocytes to restore responsiveness to IL-7.
    Mol Ther. 2009 May;17(5):880-8 PMID: 19259067
  91. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates.
    J Clin Invest. 2008 Jan;118(1):294-305 PMID: 18060041
  92. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia.
    Leukemia. 2004 Apr;18(4):676-84 PMID: 14961035
  93. Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product.
    J Immunol. 1998 Sep 15;161(6):2791-7 PMID: 9743337
  94. A high throughput microelectroporation device to introduce a chimeric antigen receptor to redirect the specificity of human T cells.
    Biomed Microdevices. 2010 Oct;12(5):855-63 PMID: 20574820
  95. Structure-based prediction of insertion-site preferences of transposons into chromosomes.
    Nucleic Acids Res. 2006 May 22;34(9):2803-11 PMID: 16717285
  96. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells.
    Blood. 2005 Jul 1;106(1):376-83 PMID: 15755898
  97. A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells.
    Mol Ther. 2005 Nov;12(5):933-41 PMID: 15979412
  98. New insights into the regulation of T cells by gamma(c) family cytokines.
    Nat Rev Immunol. 2009 Jul;9(7):480-90 PMID: 19543225
  99. Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells.
    J Immunol. 2007 Sep 1;179(5):3332-41 PMID: 17709550
  100. Redirecting specificity of T-cell populations for CD19 using the Sleeping Beauty system.
    Cancer Res. 2008 Apr 15;68(8):2961-71 PMID: 18413766
  101. Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells.
    Leuk Res. 2009 Sep;33(9):1255-9 PMID: 19147228
  102. Engineering T-cells with antibody-based chimeric receptors for effective cancer therapy.
    Curr Opin Mol Ther. 2005 Feb;7(1):48-55 PMID: 15732529
  103. T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells.
    Blood. 2006 Dec 1;108(12):3890-7 PMID: 16926291
  104. Modulating T-cell homeostasis with IL-7: preclinical and clinical studies.
    J Intern Med. 2009 Aug;266(2):141-53 PMID: 19623690
  105. Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene.
    Blood. 2007 Jun 15;109(12):5168-77 PMID: 17353346
  106. Immunotherapy of human cancers using gene modified T lymphocytes.
    Curr Gene Ther. 2009 Oct;9(5):396-408 PMID: 19860654
  107. Chimeric T-cell receptors: new challenges for targeted immunotherapy in hematologic malignancies.
    Haematologica. 2007 Mar;92(3):381-8 PMID: 17339188
  108. Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8 T cells.
    J Clin Invest. 2007 Feb;117(2):492-501 PMID: 17273561
  109. Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains.
    Hum Gene Ther. 2007 Aug;18(8):712-25 PMID: 17685852
  110. Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells.
    Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4518-23 PMID: 15758071
  111. Efficient stable gene transfer into human cells by the Sleeping Beauty transposon vectors.
    Methods. 2009 Nov;49(3):287-97 PMID: 19615447
  112. Expression of IL-15RA or an IL-15/IL-15RA fusion on CD8+ T cells modifies adoptively transferred T-cell function in cis.
    Eur J Immunol. 2009 Feb;39(2):491-506 PMID: 19180469
  113. Gene transfer into humans--immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction.
    N Engl J Med. 1990 Aug 30;323(9):570-8 PMID: 2381442
  114. 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 Apr;18(4):666-8 PMID: 20357779
  115. Adoptive immunotherapy for cancer: the next generation of gene-engineered immune cells.
    Tissue Antigens. 2009 Oct;74(4):277-89 PMID: 19775368
  116. 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 Dec 24;114(27):5454-63 PMID: 19880489
  117. Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma.
    PLoS One. 2009;4(3):e4749 PMID: 19270751
  118. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy.
    Cancer Res. 2009 May 1;69(9):4010-7 PMID: 19383914
  119. Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation.
    Blood. 2006 Mar 15;107(6):2294-302 PMID: 16282341
  120. Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy.
    Blood. 2006 Apr 1;107(7):2643-52 PMID: 16352804
  121. An entirely humanized CD3 zeta-chain signaling receptor that directs peripheral blood t cells to specific lysis of carcinoembryonic antigen-positive tumor cells.
    Int J Cancer. 2000 Oct 1;88(1):115-20 PMID: 10962448
  122. Stable gene transfer to human CD34(+) hematopoietic cells using the Sleeping Beauty transposon.
    Exp Hematol. 2006 Oct;34(10):1333-43 PMID: 16982326
  123. Thymidine kinase obliteration: creation of transgenic mice with controlled immune deficiency.
    Proc Natl Acad Sci U S A. 1989 Apr;86(8):2698-702 PMID: 2539597
  124. Re-targeting T-cells against cancer by gene-transfer of tumor-reactive receptors.
    Expert Opin Biol Ther. 2009 May;9(5):579-91 PMID: 19368527
  125. Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy.
    Blood. 2005 Jan 1;105(1):241-50 PMID: 15345595
  126. 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 Dec;5(12):3928-41 PMID: 10632322
  127. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma.
    Mol Ther. 2007 Apr;15(4):825-33 PMID: 17299405
  128. Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy.
    Cancer Res. 2007 Mar 15;67(6):2872-80 PMID: 17363611
  129. Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy.
    J Immunother. 2009 Feb-Mar;32(2):169-80 PMID: 19238016
  130. Monitoring the efficacy of adoptively transferred prostate cancer-targeted human T lymphocytes with PET and bioluminescence imaging.
    J Nucl Med. 2008 Jul;49(7):1162-70 PMID: 18552144
  131. Current status of genetic modification of T cells for cancer treatment.
    Cytotherapy. 2005;7(3):262-72 PMID: 16081353
  132. Long-lived antitumor CD8+ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell.
    Clin Cancer Res. 2007 Mar 15;13(6):1857-67 PMID: 17363542
  133. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer.
    Blood. 2005 Apr 15;105(8):3051-7 PMID: 15632206
  134. Efficient and stable transgene expression in human embryonic stem cells using transposon-mediated gene transfer.
    Stem Cells. 2007 Nov;25(11):2919-27 PMID: 17673526
  135. 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 Jan 15;90(2):720-4 PMID: 8421711
  136. Transduction of an IL-2 gene into human melanoma-reactive lymphocytes results in their continued growth in the absence of exogenous IL-2 and maintenance of specific antitumor activity.
    J Immunol. 2001 Dec 1;167(11):6356-65 PMID: 11714800
  137. Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo.
    J Immunol. 2008 Sep 1;181(5):3449-55 PMID: 18714017
  138. Thymidine kinase (TK) gene-transduced human lymphocytes can be highly purified, remain fully functional, and are killed efficiently with ganciclovir.
    Blood. 1997 Feb 15;89(4):1334-40 PMID: 9028956
  139. Cancer regression in patients after transfer of genetically engineered lymphocytes.
    Science. 2006 Oct 6;314(5796):126-9 PMID: 16946036
  140. Characterization of an artificial antigen-presenting cell to propagate cytolytic CD19-specific T cells.
    Leukemia. 2006 Oct;20(10):1889-92 PMID: 17041638
  141. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model.
    Blood. 2009 Jun 18;113(25):6392-402 PMID: 19377047
  142. T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect.
    Blood. 2003 Feb 15;101(4):1637-44 PMID: 12393484
  143. 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 Oct 13;106(41):17469-74 PMID: 19805141
  144. 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 Dec 1;167(11):6123-31 PMID: 11714771
  145. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience.
    J Clin Oncol. 2006 May 1;24(13):e20-2 PMID: 16648493
  146. Comparison of common gamma-chain cytokines, interleukin-2, interleukin-7, and interleukin-15 for the in vitro generation of human tumor-reactive T lymphocytes for adoptive cell transfer therapy.
    J Immunother. 2006 May-Jun;29(3):284-93 PMID: 16699371
  147. Conversion of a tumor-binding peptide identified by phage display to a functional chimeric T cell antigen receptor.
    Cancer Gene Ther. 2007 Jan;14(1):91-7 PMID: 17024231
  148. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer.
    Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6106-15 PMID: 17062687
  149. Enhanced antilymphoma efficacy of CD19-redirected influenza MP1-specific CTLs by cotransfer of T cells modified to present influenza MP1.
    Blood. 2005 Feb 15;105(4):1622-31 PMID: 15507526
  150. A transposon and transposase system for human application.
    Mol Ther. 2010 Apr;18(4):674-83 PMID: 20104209
  151. piggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies.
    Hum Gene Ther. 2010 Apr;21(4):427-37 PMID: 19905893
  152. Sleeping beauty transposon-mediated gene therapy for prolonged expression.
    Adv Genet. 2005;54:189-232 PMID: 16096013
  153. Gene therapy deserves a fresh chance.
    Nature. 2009 Oct 29;461(7268):1173 PMID: 19865117
  154. Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell-depleted stem cell transplantation.
    Blood. 2003 Feb 15;101(4):1290-8 PMID: 12393508
  155. Fulminant experimental autoimmune encephalo-myelitis induced by retrovirally mediated TCR gene transfer.
    Eur J Immunol. 2005 Jun;35(6):1822-30 PMID: 15909313
  156. Optimization of the PiggyBac transposon system for the sustained genetic modification of human T lymphocytes.
    J Immunother. 2009 Oct;32(8):826-36 PMID: 19752751
  157. IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice.
    Blood. 2010 Apr 29;115(17):3508-19 PMID: 20190192
  158. Sleeping Beauty transposon-mediated engineering of human primary T cells for therapy of CD19+ lymphoid malignancies.
    Mol Ther. 2008 Mar;16(3):580-9 PMID: 18227839
  159. 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 May;10(5):489-500 PMID: 19345145
  160. Gene transfer into genomes of human cells by the sleeping beauty transposon system.
    Mol Ther. 2003 Jul;8(1):108-17 PMID: 12842434
  161. Genetic therapies against HIV.
    Nat Biotechnol. 2007 Dec;25(12):1444-54 PMID: 18066041
  162. Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma.
    Nat Clin Pract Oncol. 2009 Jan;6(1):53-8 PMID: 19015650
  163. Chimeric T-cell receptors for the targeting of cancer cells.
    Acta Haematol. 2003;110(2-3):154-9 PMID: 14583676
  164. Safety of retroviral gene marking with a truncated NGF receptor.
    Nat Med. 2003 Apr;9(4):367-9 PMID: 12669036
Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2010-01-043737
Published
2010-08-19
Epub
2010-00-03
Pages
1035-44
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2938125
Subset
IM
Grants
NCI NIH HHS · R01 CA141303 · United States
NCI NIH HHS · R01 CA124782 · United States
NCI NIH HHS · R01CA124782 · United States
NCI NIH HHS · R01CA120956 · United States
NCI NIH HHS · R01 CA120956 · United States
External Links
PubMed source DOI: 10.1182/blood-2010-01-043737 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2