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Gene Therapy

  • Chapter
Biologic Therapy of Leukemia

Part of the book series: Contemporary Hematology ((CH))

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Abstract

Gene therapy may be defined as the introduction of nucleic acids into a cell with the intention of altering function to achieve a therapeutic benefit (1). Gene therapy approaches can be divided into the manipulation of reproductive cells to maintain a genetic modification in future generations (germ-line gene therapy) or gene transfer into more differentiated tissues, such as cells of the lung, liver, or brain, or hematopoietic cells (somatic gene therapy). Clinical gene therapy protocols for cancer are of this latter category. Cells can be genetically manipulated ex vivo, which has the clear advantage of facilitating control over the gene transfer procedure, and allows testing of the cell product before the administration of the cells therapeutically. However, protocols have been devised to target malignant cells in vivo, with the intention of correcting genetic abnormalities or to result in their eradication. The Journal of Gene Medicine Web site currently lists 596 clinical trials initiated since 1989, including 376 (63%) that are related to the treatment of malignancies, with 2389 patients enrolled in cancer-related gene therapy protocols (2). A total of 46 (8%) of all gene therapy trials focus on the treatment of leukemia or lymphoid malignancies. A review of these approaches and others being considered for therapy can be categorized into several therapeutic strategies (Table 1). However, before discussing these applications, an overview of the current means by which gene transfer and expression can be achieved is warranted.

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References

  1. Rubanyi GM. The future of human gene therapy. Mol Aspects Med 2001; 22: 113–142.

    PubMed  CAS  Google Scholar 

  2. Available at: http://www.wiley.co.uk/genetherapy/clinical/. Accessed January 02.

  3. Nishikawa M, Huang L. Nonviral vectors in the new millennium: delivery barriers in gene transfer. Hum Gene Ther 2001; 12: 861–870.

    PubMed  CAS  Google Scholar 

  4. Wolff JA. Naked DNA transport and expression in mammalian cells. Neuromus Disord 1997; 7: 314–318.

    CAS  Google Scholar 

  5. Mang G, Budker V, Williams P, Subbotin V, Wolff JA. Efficient expression of naked dna delivered intraarterially to limb muscles of nonhuman primates. Hum Gene Ther 2001; 12: 427–438.

    Google Scholar 

  6. Hartikka J, Sukhu L, Buchner C, et al. Electroporation-facilitated delivery of plasmid DNA in skeletal muscle: plasmid dependence of muscle damage and effect of poloxamer 188. Mol Ther 2001; 4: 407–415.

    PubMed  CAS  Google Scholar 

  7. Wolff JA, Williams P, Acsadi G, Jiao S, Jani A, Chong W. Conditions affecting direct gene transfer into rodent muscle in vivo. Biotechniques 1991; 11: 47485.

    Google Scholar 

  8. Aoki M, Morishita R, Muraishi A, et al. Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (Hemagglutinating Virus of Japan)-liposome method. J Mol Cell Cardiol 1997; 29: 949–959.

    PubMed  CAS  Google Scholar 

  9. Losordo DW, Vale PR, Symes JF, et al. Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 1998; 98: 2800–2804.

    PubMed  CAS  Google Scholar 

  10. Losordo DW, Vale PR, Isner JM. Gene therapy for myocardial angiogenesis. Am Heart J 1999; 138: S132 - S141.

    PubMed  CAS  Google Scholar 

  11. Lathi KG, Vale PR, Losordo DW, et al. Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease: anesthetic management and results. Anesth Analg 2001; 92: 19–25.

    PubMed  CAS  Google Scholar 

  12. Isner JM. Arterial gene transfer of naked DNA for therapeutic angiogenesis: early clinical results. Adv Drug Deliv Rev 1998; 30: 185–197.

    PubMed  CAS  Google Scholar 

  13. Drabick JJ, Glasspool-Malone J, King A, Malone RW. Cutaneous transfection and immune responses to intradermal nucleic acid vaccination are significantly enhanced by in vivo electropermeabilization. Mol Ther 2001; 3: 249–255.

    PubMed  CAS  Google Scholar 

  14. Chesnoy S, Huang L. Enhanced cutaneous gene delivery following intradermal injection of naked DNA in a high ionic strength solution. Mol Ther 2002; 5: 57–62.

    PubMed  CAS  Google Scholar 

  15. Hengge UR, Walker PS, Vogel JC. Expression of naked DNA in human, pig, and mouse skin. J Clin Invest 1996; 97: 2911–2916.

    PubMed  CAS  Google Scholar 

  16. Simoes S, Pires P, Duzgunes N, Pedrosa de Lima MC. Cationic liposomes as gene transfer vectors: barriers to successful application in gene therapy. Curr Opin Mol Ther 1999; 1: 147–157.

    PubMed  CAS  Google Scholar 

  17. Coutelle C, Williamson R. Liposomes and viruses for gene therapy of cystic fibrosis. J Aerosol Med 1996; 9: 79–88.

    PubMed  CAS  Google Scholar 

  18. Chonn A, Cullis PR. Recent advances in liposomal drug-delivery systems. Curr Opin Biotechnol 1995; 6: 698–708.

    PubMed  CAS  Google Scholar 

  19. Mologni L, Marchesi E, Nielsen PE, Gambacorti-Passerini C. Inhibition of promyelocytic leukemia (PML)/retinoic acid receptor-alpha and PML expression in acute promyelocytic leukemia cells by anti-PML peptide nucleic acid. Cancer Res 2001; 61: 5468–5473.

    PubMed  CAS  Google Scholar 

  20. Kitajima I, Hanyu N, Soejima Y, et al. Efficient transfer of synthetic ribozymes into cells using hemagglutinating virus of Japan (HVJ)-cationic liposomes. Application for ribozymes that target human t-cell leukemia virus type I tax/rex mRNA. J Biol Chem 1997;272:27, 099–27, 106.

    Google Scholar 

  21. Konopleva M, Tari AM, Estrov Z, et al. Liposomal Bc1–2 antisense oligonucleotides enhance proliferation, sensitize acute myeloid leukemia to cytosine-arabinoside, and induce apoptosis independent of other antiapoptotic proteins. Blood 2000; 95: 3929–3938.

    PubMed  CAS  Google Scholar 

  22. Tari AM, Tucker SD, Deisseroth A, Lopez-Berestein G. Liposomal delivery of methylphosphonate antisense oligodeoxynucleotides in chronic myelogenous leukemia. Blood 1994; 84: 601–607.

    PubMed  CAS  Google Scholar 

  23. Wu Y, Yu L, McMahon R, Rossi JJ, Forman SJ, Snyder DS. Inhibition of bcr-abl oncogene expression by novel deoxyribozymes (DNAzymes). Hum Gene Ther 1999; 10: 2847–2857.

    PubMed  CAS  Google Scholar 

  24. Mascarenhas L, Stripecke R, Case SS, Xu D, Weinberg KI, Kohn DB. Gene delivery to human B-precursor acute lymphoblastic leukemia cells. Blood 1998; 92: 3537–3545.

    PubMed  CAS  Google Scholar 

  25. Nabel EG, Plautz G, Nabel GJ. Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science 1990; 249: 1285–1258.

    PubMed  CAS  Google Scholar 

  26. Dass CR, Walker TL, Burton MA, Decruz EE. Enhanced anticancer therapy mediated by specialized liposomes. J Pharm Pharmacol 1997; 49: 972–925.

    PubMed  CAS  Google Scholar 

  27. Ledley FD. Nonviral gene therapy: the promise of genes as pharmaceutical products. Hum Gene Ther 1995; 6: 1129–1144.

    PubMed  CAS  Google Scholar 

  28. Verma IM, Somia N. Gene therapy-promises, problems and prospects. Nature 1997; 389: 239–242.

    PubMed  CAS  Google Scholar 

  29. Xiang J, Qi Y, Chen Y. Inhibition of established tumor growth in syngeneic mice by local inoculation of engineered mouse myeloma cells secreting a recombinant fusion protein RM4/TNF. Cancer Gene Ther 1997; 4: 353–358.

    PubMed  CAS  Google Scholar 

  30. Laning J, Kawasaki H, Tanaka E, Luo Y, Dorf ME. Inhibition of in vivo tumor growth by the beta chemokine, TCA3. J Immunol 1994; 153: 4625–4635.

    PubMed  CAS  Google Scholar 

  31. Turner JG, Tan J, Crucian BE, et al. Broadened clinical utility of gene gun-mediated, granulocyte-macrophage colony-stimulating factor cDNA-based tumor cell vaccines as demonstrated with a mouse myeloma model. Hum Gene Ther 1998; 9: 1121–1130.

    PubMed  CAS  Google Scholar 

  32. Wright MJ, Wightman LM, Lilley C, et al. In vivo myocardial gene transfer: optimization, evaluation and direct comparison of gene transfer vectors. Basic Res Cardiol 2001; 96: 227–236.

    PubMed  CAS  Google Scholar 

  33. Somia N, Verma IM. Gene therapy: trials and tribulations. Nat Rev Genet 2000; 1: 91–99.

    PubMed  CAS  Google Scholar 

  34. SoRelle R. Human gene therapy: scienj under fire. Circulation 2000; 101: E9023 - E9024.

    PubMed  CAS  Google Scholar 

  35. Pfeifer A, Verma IM. Gene therapy: promises and problems. Annu Rev Genomics Hum Genet 2001; 2: 177–211.

    PubMed  CAS  Google Scholar 

  36. Brenner MK. Gene transfer and the treatment of haematological malignancy. J Intern Med 2001; 249: 345–358.

    PubMed  CAS  Google Scholar 

  37. Watanabe S, Temin HM. Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors. Mol Cell Biol 1983; 3: 2241–2249.

    PubMed  CAS  Google Scholar 

  38. Mann R, Mulligan RC, Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 1983; 33: 153–159.

    PubMed  CAS  Google Scholar 

  39. Wang H, Kavanaugh MP, North RA, Kabat D. Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter. Nature 1991; 352: 729–731.

    PubMed  CAS  Google Scholar 

  40. Kim JW, Closs EI, Albritton LM, Cunningham JM. Transport of cationic amino acids by the mouse ecotropic retrovirus receptor. Nature 1991; 352: 725–728.

    PubMed  CAS  Google Scholar 

  41. Miller DG, Miller AD. A family of retroviruses that utilize related phosphate transporters for cell entry. J Virol 1994; 68: 8270–8276.

    PubMed  CAS  Google Scholar 

  42. Kavanaugh MP, Miller DG, Zhang W, et al. Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters. Proc Natl Acad Sci USA 1994; 91: 7071–7075.

    PubMed  CAS  Google Scholar 

  43. Bauer TR, Jr., Miller AD, Hickstein DD. Improved transfer of the leukocyte integrin CD 18 subunit into hematopoietic cell lines by using retroviral vectors having a gibbon ape leukemia virus envelope. Blood 1995; 86: 2379–2387.

    PubMed  CAS  Google Scholar 

  44. Lam JS, Reeves ME, Cowherd R, Rosenberg SA, Hwu P. Improved gene transfer into human lymphocytes using retroviruses with the gibbon ape leukemia virus envelope. Hum Gene Ther 1996; 7: 1415–1422.

    PubMed  CAS  Google Scholar 

  45. Porter CD, Collins MK, Tailor CS, et al. Comparison of efficiency of infection of human gene therapy target cells via four different retroviral receptors. Hum Gene Ther 1996; 7: 913–919.

    PubMed  CAS  Google Scholar 

  46. Gallardo HF, Tan C, Ory D, Sadelain M. Recombinant retroviruses pseudotyped with the vesicular stomatitis virus G glycoprotein mediate both stable gene transfer and pseudo-transduction in human peripheral blood lymphocytes. Blood 1997; 90: 952–957.

    PubMed  CAS  Google Scholar 

  47. Thomsen S, Vogt B, von Laer D, et al. Lack of functional Pit-1 and Pit-2 expression on hematopoietic stem cell lines. Acta Haematol 1998; 99: 148–155.

    PubMed  CAS  Google Scholar 

  48. Arai T, Matsumoto K, Saitoh K, et al. A new system for stringent, high-titer vesicular stomatitis virus G protein-pseudotyped retrovirus vector induction by introduction of Cre recombinase into stable prepackaging cell lines. J Virol 1998; 72: 1115–1121.

    PubMed  CAS  Google Scholar 

  49. Blaese RM, Culver KW, Miller AD, et al. T lymphocyte-directed gene therapy for ADASCID: initial trial results after 4 years. Science 1995; 270: 475–480.

    PubMed  CAS  Google Scholar 

  50. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000; 288: 669–672.

    PubMed  CAS  Google Scholar 

  51. Available at: http://www4.od.nih.gov/oba/rdna.htm. Accessed.

  52. Vanin EF, Kaloss M, Broscius C, Nienhuis AW. Characterization of replication-competent retroviruses from nonhuman primates with virus-induced T-cell lymphomas and observations regarding the mechanism of oncogenesis. J Virol 1994; 68: 4241–42450.

    PubMed  CAS  Google Scholar 

  53. Purcell DF, Broscius CM, Vanin EF, Buckler CE, Nienhuis AW, Martin MA. An array of murine leukemia virus-related elements is transmitted and expressed in a primate recipient of retroviral gene transfer. J Virol 1996; 70: 887–897.

    PubMed  CAS  Google Scholar 

  54. Donahue RE, Kessler SW, Bodine D, et al. Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. J Exp Med 1992; 176: 1125–1135.

    PubMed  CAS  Google Scholar 

  55. Cosset FL, Takeuchi Y, Battini JL, Weiss RA, Collins MK. High-titer packaging cells producing recombinant retroviruses resistant to human serum. J Virol 1995; 69: 7430–7436.

    PubMed  CAS  Google Scholar 

  56. Shimizu K, Miyao Y, Tamura M, et al. Infectious retrovirus is inactivated by serum but not by cerebrospinal fluid or fluid from tumor bed in patients with malignant glioma. Jpn J Cancer Res 1995; 86: 1010–1013.

    PubMed  CAS  Google Scholar 

  57. Rainov NG, Kramm CM, Banning U, et al. Immune response induced by retrovirus-mediated HSV-tk/GCV pharmacogene therapy in patients with glioblastoma multiforme. Gene Ther 2000; 7: 1853–1858.

    PubMed  CAS  Google Scholar 

  58. Rainov NG. A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther 2000; 11: 2389–2401.

    PubMed  CAS  Google Scholar 

  59. Culver KW, Ram Z, Wallbridge S, Ishii H, Oldfield EH, Blaese RM. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 1992; 256: 1550–1552.

    PubMed  CAS  Google Scholar 

  60. Buchschacher GL, Jr., Wong-Staal F. Development of lentiviral vectors for gene therapy for human disease. Blood 2000; 95: 2499–2504.

    PubMed  CAS  Google Scholar 

  61. Naldini L, Blomer U, Gage FH, Trono D, Verma IM. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA 1996; 93: 11382–11388.

    PubMed  CAS  Google Scholar 

  62. Naldini L. Lentiviruses as gene transfer agents for delivery to non-dividing cells. Curr Opin Biotechnol 1998; 9: 457–463.

    PubMed  CAS  Google Scholar 

  63. Lewis P, Hensel M, Emerman M. Human immunodeficiency virus infection of cells arrested in the cell cycle. Embo J 1992; 11: 3053–3058.

    PubMed  CAS  Google Scholar 

  64. Lewis PF, Emerman M. Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol 1994; 68: 510–516.

    PubMed  CAS  Google Scholar 

  65. Douglas JL, Lin WY, Parris ML, Veres G. Efficient human immunodeficiency virus-based vector transduction of unstimulated human mobilized peripheral blood CD34+ cells in the SCID- hu Thy/Liv model of human T cell lymphopoiesis. Hum Gene Ther 2001; 12: 401–413.

    PubMed  CAS  Google Scholar 

  66. Guenechea G, Gan OI, Inamitsu T, et al. Transduction of human CD34+ CD38- bone marrow and cord blood-derived SCID-repopulating cells with third-generation lentiviral vectors. Mol Ther 2000; 1: 566–573.

    PubMed  CAS  Google Scholar 

  67. Akkina RK, Walton RM, Chen ML, Li QX, Planelles V, Chen IS. High-efficiency gene transfer into CD34+ cells with a human immunodeficiency virus type 1-based retroviral vector pseudotyped with vesicular stomatitis virus envelope glycoprotein G. J Virol 1996; 70: 2581–2585.

    PubMed  CAS  Google Scholar 

  68. Gatlin J, Padgett A, Melkus MW, Kelly PF, Garcia JV. Long-term engraftment of nonobese diabetic/severe combined immunodeficient mice with human CD34+ cells transduced by a self-inactivating human immunodeficiency virus type 1 vector. Hum Gene Ther 2001; 12: 1079–1089.

    PubMed  CAS  Google Scholar 

  69. Kumar M, Keller B, Makalou N, Sutton RE. Systematic determination of the packaging limit of lentiviral vectors. Hum Gene Ther 2001; 12: 1893–1905.

    PubMed  CAS  Google Scholar 

  70. Farson D, Witt R, McGuinness R, et al. A new-generation stable inducible packaging cell line for lentiviral vectors. Hum Gene Ther 2001; 12: 981–997.

    PubMed  CAS  Google Scholar 

  71. Diaz RM, Bateman A, Emiliusen L, et al. A lentiviral vector expressing a fusogenic glycoprotein for cancer gene therapy. Gene Ther 2000; 7: 1656–1663.

    PubMed  CAS  Google Scholar 

  72. Corbeau P, Kraus G, Wong-Staal F Transduction of human macrophages using a stable HIV-1/HIV-2-derived gene delivery system. Gene Ther 1998; 5: 99–104.

    PubMed  CAS  Google Scholar 

  73. Sadaie MR, Zamani M, Whang S, Sistron N, Arya SK. Towards developing HIV-2 lentivirus-based retroviral vectors for gene therapy: dual gene expression in the context of HIV-2 LTR and Tat. J Med Virol 1998; 54: 118–128.

    PubMed  CAS  Google Scholar 

  74. Pandya S, Boris-Lawrie K, Leung NJ, Akkina R, Planelles V. Development of an Rev-independent, minimal simian immunodeficiency virus-derived vector system. Hum Gene Ther 2001; 12: 847–857.

    PubMed  CAS  Google Scholar 

  75. White SM, Renda M, Nam NY, et al. Lentivirus vectors using human and simian immunodeficiency virus elements. J Virol 1999; 73: 2832–2840.

    PubMed  CAS  Google Scholar 

  76. Browning MT, Schmidt RD, Lew KA, Rizvi TA. Primate and feline lentivirus vector RNA packaging and propagation by heterologous lentivirus virions. J Virol 2001; 75: 5129–5140.

    PubMed  CAS  Google Scholar 

  77. Yamada K, Olsen JC, Patel M, Rao KW, Walsh CE. Functional correction of fanconi anemia group C hematopoietic cells by the use of a novel lentiviral vector. Mol Ther 2001; 3: 485–490.

    PubMed  CAS  Google Scholar 

  78. Olsen JC. Gene transfer vectors derived from equine infectious anemia virus. Gene Ther 1998; 5: 1481–1487.

    PubMed  CAS  Google Scholar 

  79. Kochanek S. High-capacity adenoviral vectors for gene transfer and somatic gene therapy. Hum Gene Ther 1999; 10: 2451–2459.

    PubMed  CAS  Google Scholar 

  80. Harui A, Suzuki S, Kochanek S, Mitani K. Frequency and stability of chromosomal integration of adenovirus vectors. J Virol 1999; 73: 6141–6146.

    PubMed  CAS  Google Scholar 

  81. Yeh P, Perricaudet M. Advances in adenoviral vectors: from genetic engineering to their biology. FASEB J 1997; 11: 615–623.

    CAS  Google Scholar 

  82. Morsy MA, Gu M, Motzel S, et al. An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene. Proc Natl Acad Sci USA 1998; 95: 7866–7871.

    PubMed  CAS  Google Scholar 

  83. Simon RH, Engelhardt JF, Yang Y, et al. Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: toxicity study. Hum Gene Ther 1993; 4: 771–780.

    PubMed  CAS  Google Scholar 

  84. Molnar-Kimber KL, Sterman DH, Chang M, et al. Impact of preexisting and induced humoral and cellular immune responses in an adenovirus-based gene therapy phase I clinical trial for localized mesothelioma. Hum Gene Ther 1998; 9: 2121–2133.

    PubMed  CAS  Google Scholar 

  85. Qian HS, Channon K, Neplioueva V, et al. Improved adenoviral vector for vascular gene therapy: beneficial effects on vascular function and inflammation. Circ Res 2001; 88: 911–917.

    PubMed  CAS  Google Scholar 

  86. Wang Q, Finer MH. Second-generation adenovirus vectors. Nat Med 1996; 2: 714–716.

    PubMed  CAS  Google Scholar 

  87. Torrent C, Jullien C, Klatzmann D, Perricaudet M, Yeh P. Transgene amplification and persistence after delivery of retroviral vector and packaging functions with El/E4-deleted adenoviruses. Cancer Gene Ther 2000; 7: 1135–1144.

    PubMed  CAS  Google Scholar 

  88. Yeh P, Dedieu JF, Orsini C, Vigne E, Denefle P, Perricaudet M. Efficient dual transcomplementation of adenovirus El and E4 regions from a 293-derived cell line expressing a minimal E4 functional unit. J Virol 1996; 70: 559–565.

    PubMed  CAS  Google Scholar 

  89. Parks RI, Chen L, Anton M, Sankar U, Rudnicki MA, Graham FL. A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc Natl Acad Sci USA 1996; 93: 13565–13570.

    PubMed  CAS  Google Scholar 

  90. Schiedner G, Morral N, Parks RJ, et al. Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity. Nat Genet 1998; 18: 180–183.

    PubMed  CAS  Google Scholar 

  91. Kafri T, Morgan D, Krahl T, Sarvetnick N, Sherman L, Verma I. Cellular immune response to adenoviral vector infected cells does not require de novo viral gene expression: implications for gene therapy. Proc Natl Acad Sci USA 1998; 95: 11377–11382.

    PubMed  CAS  Google Scholar 

  92. Marshall E. Gene therapy death prompts review of adenovirus vector. Science 1999; 286: 2244–2245.

    PubMed  CAS  Google Scholar 

  93. Lehrman S. Virus treatment questioned after gene therapy death. Nature 1999; 401: 517–518.

    PubMed  CAS  Google Scholar 

  94. Raper SE, Yudkoff M, Chirmule N, et al. A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum Gene Ther 2002; 13: 163–175.

    PubMed  CAS  Google Scholar 

  95. Marshall E. Gene therapy on trial. Science 2000; 288: 951–957.

    PubMed  CAS  Google Scholar 

  96. Stedman H, Wilson JM, Finke R, Kleckner AL, Mendell J. Phase I clinical trial utilizing gene therapy for limb girdle muscular dystrophy: alpha-, beta-, gamma-, or delta-sarcoglycan gene delivered with intramuscular instillations of adeno-associated vectors. Hum Gene Ther 2000; 11: 777–790.

    PubMed  CAS  Google Scholar 

  97. Habib NA, Hodgson HJ, Lemoine N, Pignatelli M. A phase I/II study of hepatic artery infusion with wtp53-CMV-Ad in metastatic malignant liver tumors. Hum Gene Ther 1999; 10: 2019–2034.

    PubMed  CAS  Google Scholar 

  98. Sung MW, Yeh HC, Thung SN, et al. Intratumoral adenovirus-mediated suicide gene transfer for hepatic metastases from colorectal adenocarcinoma: results of a phase I clinical trial. Mol Ther 2001; 4: 182–191.

    PubMed  CAS  Google Scholar 

  99. Wilson JM, Engelhardt JF, Grossman M, Simon RH, Yang Y. Gene therapy of cystic fibrosis lung disease using El deleted adenoviruses: a phase I trial. Hum Gene Ther 1994; 5: 501–519.

    PubMed  CAS  Google Scholar 

  100. Boucher RC, Knowles MR, Johnson LG, et al. Gene therapy for cystic fibrosis using El-deleted adenovirus: a phase I trial in the nasal cavity. The University of North Carolina at Chapel Hill. Hum Gene Ther 1994; 5: 615–639.

    PubMed  CAS  Google Scholar 

  101. Perricone MA, Morris JE, Pavelka K, et al. Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. II. Transfection efficiency in airway epithelium. Hum Gene Ther 2001; 12: 1383–1394.

    PubMed  CAS  Google Scholar 

  102. Cohen ZR, Duvdevani R, Nass D, Hadani M, Ram Z. Intraarterial delivery of genetic vectors for the treatment of malignant brain tumors. Isr Med Assoc J 2001; 3: 117–120.

    PubMed  CAS  Google Scholar 

  103. Sandmair AM, Loimas S, Puranen P, et al. Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. Hum Gene Ther 2000; 11: 2197–2205.

    PubMed  CAS  Google Scholar 

  104. Adachi Y, Tamiya T, Ichikawa T, et al. Experimental gene therapy for brain tumors using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene with 5-fluorocytosine. Hum Gene Ther 2000; 11: 77–89.

    PubMed  CAS  Google Scholar 

  105. Schwarzenberger P, Huang W, Oliver P, Osidipe T, Theodossiou C, Kolls JK. Poly-Llysine-based molecular conjugate vectors: a high efficiency gene transfer system for human progenitor and leukemia cells. Am J Med Sci 2001; 321: 129–136.

    PubMed  CAS  Google Scholar 

  106. Blagosklonny MV, el-Deiry WS. In vitro evaluation of a p53-expressing adenovirus as an anti-cancer drug. Int J Cancer 1996; 67: 386–392.

    PubMed  CAS  Google Scholar 

  107. Yotnda P, Onishi H, Heslop HE, et al. Efficient infection of primitive hematopoietic stem cells by modified adenovirus. Gene Ther 2001; 8: 930–937.

    PubMed  CAS  Google Scholar 

  108. Meeker TC, Lay LT, Wroblewski JM, Turturro F, Li Z, Seth P. Adenoviral vectors efficiently target cell lines derived from selected lymphocytic malignancies, including anaplastic large cell lymphoma and Hodgkin’s disease. Clin Cancer Res 1997; 3: 357–364.

    PubMed  CAS  Google Scholar 

  109. Medina DJ, Sheay W, Goodell L, et al. Adenovirus-mediated cytotoxicity of chronic lymphocytic leukemia cells. Blood 1999; 94: 3499–3508.

    PubMed  CAS  Google Scholar 

  110. Garcia-Castro J, Segovia JC, Garcia-Sanchez F, et al. Selective transduction of murine myelomonocytic leukemia cells (WEHI- 3B) with regular and RGD-adenoviral vectors. Mol Ther 2001; 3: 70–77.

    PubMed  CAS  Google Scholar 

  111. Clark PR, Stopeck AT, Brailey JL, et al. Polycations and cationic lipids enhance adenovirus transduction and transgene expression in tumor cells. Cancer Gene Ther 1999; 6: 437–446.

    PubMed  CAS  Google Scholar 

  112. Gonzalez R, Vereecque R, Wickham TJ, et al. Transduction of bone marrow cells by the AdZ.F(pK7) modified adenovirus demonstrates preferential gene transfer in myeloma cells. Hum Gene Ther 1999; 10: 2709–2717.

    PubMed  CAS  Google Scholar 

  113. Kipps TJ, Chu P, Wierda WG. Immunogenetic therapy for B-cell malignancies. Semin Oncol2000; 27: 104–109.

    PubMed  CAS  Google Scholar 

  114. Takahashi S, Yotnda P, Rousseau RF, et al. Transgenic expression of CD40L and interleukin-2 induces an autologous antitumor immune response in patients with non-Hodgkin’s lymphoma. Cancer Gene Ther 2001; 8: 378–387.

    PubMed  CAS  Google Scholar 

  115. Wong CP, Levy R. Recombinant adenovirus vaccine encoding a chimeric T-cell antigen receptor induces protective immunity against a T-cell lymphoma. Cancer Res 2000; 60: 2689–2695.

    PubMed  CAS  Google Scholar 

  116. Dotti G, Savoldo B, Takahashi S, et al. Adenovector-induced expression of human-CD40ligand (hCD40L) by multiple myeloma cells. A model for immunotherapy. Exp Hematol 2001; 29: 952–961.

    PubMed  CAS  Google Scholar 

  117. Wierda WG, Cantwell MJ, Woods SJ, Rassenti LZ, Prussak CE, Kipps TJ. CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia. Blood 2000; 96: 2917–2924.

    PubMed  CAS  Google Scholar 

  118. Takahashi S, Rousseau RF, Yotnda P, et al. Autologous antileukemic immune response induced by chronic lymphocytic leukemia B cells expressing the CD40 ligand and interleukin 2 transgenes. Hum Gene Ther 2001; 12: 659–670.

    PubMed  CAS  Google Scholar 

  119. Xiao X, Li J, McCown TJ, Samulski RI. Gene transfer by adeno-associated virus vectors into the central nervous system. Exp Neurol 1997; 144: 113–124.

    PubMed  CAS  Google Scholar 

  120. Kotin RM, Menninger JC, Ward DC, Berns KI. Mapping and direct visualization of a region-specific viral DNA integration site on chromosome 19q13-qter. Genomics 1991; 10: 831–834.

    PubMed  CAS  Google Scholar 

  121. Kotin RM, Siniscalco M, Samulski RI, et al. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 1990; 87: 2211–2215.

    PubMed  CAS  Google Scholar 

  122. Ponnazhagan S, Erikson D, Kearns WG, et al. Lack of site-specific integration of the recombinant adeno-associated virus 2 genomes in human cells. Hum Gene Ther 1997; 8: 275–284.

    PubMed  CAS  Google Scholar 

  123. Kearns WG, Afione SA, Fulmer SB, et al. Recombinant adeno-associated virus (AAVCFTR) vectors do not integrate in a site-specific fashion in an immortalized epithelial cell line. Gene Ther 1996; 3: 748–755.

    PubMed  CAS  Google Scholar 

  124. Siegl G, Bates RC, Berns KI, et al. Characteristics and taxonomy of Parvoviridae. Intervirology 1985; 23: 61–73.

    PubMed  CAS  Google Scholar 

  125. Muzyczka N. Use of adeno-associated virus as a general transduction vector for mammalian cells. Curr Top MicrobiolImmunol 1992; 158: 97–129.

    CAS  Google Scholar 

  126. Dong JY, Fan PD, Frizzell RA. Quantitative analysis of the packaging capacity of recombinant adeno-associated virus. Hum Gene Ther 1996; 7: 2101–2112.

    PubMed  CAS  Google Scholar 

  127. Duan D, Sharma P, Yang J, et al. Circular intermediates of recombinant adeno-associated virus have defined structural characteristics responsible for long-term episomal persistence in muscle tissue. J Virol 1998; 72: 8568–8577.

    PubMed  CAS  Google Scholar 

  128. Xiao X, Li J, Samulski RJ. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J Virol 1998; 72: 2224–2232.

    PubMed  CAS  Google Scholar 

  129. Duan D, Yue Y, Engelhardt JF. Expanding AAV packaging capacity with trans-splicing or overlapping vectors: a quantitative comparison. Mol Ther 2001; 4: 383–391.

    PubMed  CAS  Google Scholar 

  130. Duan D, Yan Z, Yue Y, Ding W, Engelhardt JF. Enhancement of muscle gene delivery with pseudotyped adeno-associated virus type 5 correlates with myoblast differentiation. J Virol 2001; 75: 7662–7671.

    PubMed  CAS  Google Scholar 

  131. Xiao W, Chirmule N, Berta SC, McCullough B, Gao G, Wilson JM. Gene therapy vectors based on adeno-associated virus type 1. J Virol 1999; 73: 3994–4003.

    PubMed  CAS  Google Scholar 

  132. Bjorklund A, Kirik D, Rosenblad C, Georgievska B, Lundberg C, Mandel RI. Towards a neuroprotective gene therapy for Parkinson’s disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res 2000; 886: 82–98.

    PubMed  CAS  Google Scholar 

  133. Hartigan-O’Connor D, Chamberlain JS. Developments in gene therapy for muscular dystrophy. Microsc Res Tech 2000; 48: 223–238.

    PubMed  Google Scholar 

  134. Kay MA, Manno CS, Ragni MV, et al. Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector. Nat Genet 2000; 24: 257–261.

    PubMed  CAS  Google Scholar 

  135. High KA. Gene therapy: a 2001 perspective. Haemophilia 2001; 7 (suppl 1): 23–27.

    PubMed  CAS  Google Scholar 

  136. Ponnazhagan S, Mukherjee P, Wang XS, et al. Adeno-associated virus type 2-mediated transduction in primary human bone marrow-derived CD34+ hematopoietic progenitor cells: donor variation and correlation of transgene expression with cellular differentiation. J Virol 1997; 71: 8262–8267.

    PubMed  CAS  Google Scholar 

  137. Ponnazhagan S, Yoder MC, Srivastava A. Adeno-associated virus type 2-mediated transduction of murine hematopoietic cells with long-term repopulating ability and sustained expression of a human globin gene in vivo. J Virol 1997; 71: 3098–3104.

    PubMed  CAS  Google Scholar 

  138. Goodman S, Xiao X, Donahue RE, et al. Recombinant adeno-associated virus-mediated gene transfer into hematopoietic progenitor cells. Blood 1994; 84: 1492–1500.

    PubMed  CAS  Google Scholar 

  139. Anderson R, Macdonald I, Corbett T, Hacking G, Lowdell MW, Prentice HG. Construction and biological characterization of an interleukin-12 fusion protein (Flexi-12): delivery to acute myeloid leukemic blasts using adeno-associated virus. Hum Gene Ther 1997; 8: 1125–1135.

    PubMed  CAS  Google Scholar 

  140. Luo F, Zhou SZ, Cooper S, et al. Adeno-associated virus 2-mediated gene transfer and functional expression of the human granulocyte-macrophage colony-stimulating factor. Exp Hematol 1995; 23: 1261–1267.

    PubMed  CAS  Google Scholar 

  141. Omori F, Messner HA, Ye C, et al. Nontargeted stable integration of recombinant adenoassociated virus into human leukemia and lymphoma cell lines as evaluated by fluorescence in situ hybridization. Hum Gene Ther 1999; 10: 537–543.

    PubMed  CAS  Google Scholar 

  142. Ponnazhagan S, Weigel KA, Raikwar SP, Mukherjee P, Yoder MC, Srivastava A. Recombinant human parvovirus B19 vectors: erythroid cell-specific delivery and expression of transduced genes. J Virol 1998; 72: 5224–5230.

    PubMed  CAS  Google Scholar 

  143. Rabinowitz JE, Samulski R.I. Building a better vector: the manipulation of AAV virions. Virology 2000; 278: 301–308.

    PubMed  CAS  Google Scholar 

  144. Robbins PD, Ghivizzani SC. Viral vectors for gene therapy. Pharmacol Ther 1998; 80: 35–47.

    PubMed  CAS  Google Scholar 

  145. Burton EA, Wechuck JB, Wendell SK, Goins WF, Fink DJ, Glorioso JC. Multiple applications for replication-defective herpes simplex virus vectors. Stem Cells 2001; 19: 358–377.

    PubMed  CAS  Google Scholar 

  146. Ozuer A, Wechuck JB, Goins WF, Wolfe D, Glorioso JC, Ataai MM. Effect of genetic background and culture conditions on the production of herpesvirus-based gene therapy vectors. Biotechnol Bioeng 2002; 77: 685–692.

    PubMed  CAS  Google Scholar 

  147. Carlezon WA, Jr., Nestler EJ, Neve RL. Herpes simplex virus-mediated gene transfer as a tool for neuropsychiatric research. Crit Rev Neurobiol 2000; 14: 47–67.

    PubMed  CAS  Google Scholar 

  148. Wood MJ, Byrnes AP, Pfaff DW, Rabkin SD, Charlton HM. Inflammatory effects of gene transfer into the CNS with defective HSV-1 vectors. Gene Ther 1994; 1: 283–291.

    PubMed  CAS  Google Scholar 

  149. Maguir-Zeis KA, Bowers WJ, Federoff HJ. HSV vector-mediated gene delivery to the central nervous system. Curr Opin Mol Ther 2001; 3: 482–490.

    Google Scholar 

  150. Markert JM, Medlock MD, Rabkin SD, et al. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther 2000; 7: 867–874.

    PubMed  CAS  Google Scholar 

  151. Tolba KA, Bowers WJ, Hilchey SP, et al. Development of herpes simplex virus-1 ampliconbased immunotherapy for chronic lymphocytic leukemia. Blood 2001; 98: 287–295.

    PubMed  CAS  Google Scholar 

  152. Eling DJ, Johnson PA, Sharma S, Tufaro F, Kipps TJ. Chronic lymphocytic leukemia B cells are highly sensitive to infection by herpes simplex virus-1 via herpesvirus-entry-mediator A. Gene Ther 2000; 7: 1210–1216.

    PubMed  CAS  Google Scholar 

  153. Wu A, Mazumder A, Martuza RL, et al. Biological purging of breast cancer cells using an attenuated replication-competent herpes simplex virus in human hematopoietic stem cell transplantation. Cancer Res 2001; 61: 3009–3015.

    PubMed  CAS  Google Scholar 

  154. Rosenberg SA, Aebersold P, Cometta K, et al. Gene transfer into humans-immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 1990; 323: 570–578.

    PubMed  CAS  Google Scholar 

  155. Brenner MK, Rill DR, Moen RC, et al. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet 1993; 341: 85–86.

    PubMed  CAS  Google Scholar 

  156. Deisseroth AB, Zu Z, Claxton D, et al. Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML. Blood 1994; 83: 3068–3076.

    PubMed  CAS  Google Scholar 

  157. Bachier CR, Giles RE, Ellerson D, et al. Hematopoietic retroviral gene marking in patients with follicular non-Hodgkin’s lymphoma. Leukemia Lymphoma 1999; 32: 279–288.

    PubMed  CAS  Google Scholar 

  158. Dunbar CE, Cottler-Fox M, O’Shaughnessy JA, et al. Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation. Blood 1995; 85: 3048–3057.

    PubMed  CAS  Google Scholar 

  159. Stewart AK, Sutherland DR, Nanji S, et al. Engraftment of gene-marked hematopoietic progenitors in myeloma patients after transplant of autologous long-term marrow cultures. Hum Gene Ther 1999; 10: 1953–1964.

    PubMed  CAS  Google Scholar 

  160. Brenner MK. Hematological malignancies. FASEB J 1997; 11: 640–648.

    CAS  Google Scholar 

  161. Miller AR, Skotzko MJ, Rhoades K, et al. Simultaneous use of two retroviral vectors in human gene marking trials: feasibility and potential applications. Hum Gene Ther 1992; 3: 619–624.

    PubMed  CAS  Google Scholar 

  162. Heslop HE, Rooney CM, Brenner MK. Gene-marking and haemopoietic stem-cell transplantation. Blood Rev 1995; 9: 220–225.

    PubMed  CAS  Google Scholar 

  163. Cornetta K, Srour EF, Moore A, et al. Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia. Hum Gene Ther 1996; 7: 1323–1329.

    PubMed  CAS  Google Scholar 

  164. Rooney CM, Smith CA, Ng CY, et al. Use of gene-modified virus-specific T-lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 1995; 345: 9–13.

    PubMed  CAS  Google Scholar 

  165. Heslop H, Rooney C, Brenner M, et al. Administration of neomycin resistance gene-marked EBV-specific cytotoxic T-lymphocytes as therapy for patients receiving a bone marrow transplant for relapsed EBV-positive Hodgkin disease. Hum Gene Ther 2000; 11: 1465–1475.

    PubMed  CAS  Google Scholar 

  166. Savoldo B, Cubbage ML, Durett AG, et al. Generation of EBV-Specific CD4(+) cytotoxic T cells from virus naive individuals. Jlmmunol 2002; 168: 909–918.

    CAS  Google Scholar 

  167. Liu Z, Savoldo B, Huls H, et al. Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes for the prevention and treatment of EBV-associated post-transplant lymphomas. Recent Results Cancer Res 2002; 159: 123–133.

    PubMed  CAS  Google Scholar 

  168. Gahn B, Siller-Lopez F, Pirooz AD, et al. Adenoviral gene transfer into dendritic cells efficiently amplifies the immune response to LMP2A antigen: a potential treatment strategy for Epstein-Barr virus-positive Hodgkin’s lymphoma. Int J Cancer 2001; 93: 706–713.

    PubMed  CAS  Google Scholar 

  169. Bagnis C, Chabannon C, Gravis G, et al. Transient detection of ß-galactosidase activity in hematopoietic cells, following reinjection of retrovirally marked autologous blood progenitors in patients with breast or ovarian cancer receiving high-dose chemotherapy. Exp Hematol 2002; 30: 108–115.

    PubMed  CAS  Google Scholar 

  170. Heim DA, Hanazono Y, Giri N, et al. Introduction of a xenogeneic gene via hematopoietic stem cells leads to specific tolerance in a rhesus monkey model. Mol Ther 2000; 1: 533–544.

    PubMed  CAS  Google Scholar 

  171. Finke JH, Zea AH, Stanley J, et al. Loss of T-cell receptor zeta chain and p561ck in T-cells infiltrating human renal cell carcinoma. Cancer Res 1993; 53: 5613–5616.

    PubMed  CAS  Google Scholar 

  172. Isomaki P, Panesar M, Annenkov A, et al. Prolonged exposure of T cells to TNF down-regulates TCR zeta and expression of the TCR/CD3 complex at the cell surface. J Immunol 2001; 166: 5495–5507.

    PubMed  CAS  Google Scholar 

  173. Horiguchi S, Petersson M, Nakazawa T, et al. Primary chemically induced tumors induce profound immunosuppression concomitant with apoptosis and alterations in signal transduction in T cells and NK cells. Cancer Res 1999; 59: 2950–2956.

    PubMed  CAS  Google Scholar 

  174. Mizoguchi H, O’ Shea JJ, Longo DL, Loeffler CM, Mc Vicar DW, Ochoa AC. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 1992; 258: 1795–1798.

    PubMed  CAS  Google Scholar 

  175. Nagata S. Fas ligand and immune evasion. Nat Med 1996; 2: 1306–1307.

    PubMed  CAS  Google Scholar 

  176. Garrido F, Cabrera T, Concha A, Glew S, Ruiz-Cabello F, Stem PL. Natural history of HLA expression during tumour development. Immunol Today 1993; 14: 491–499.

    PubMed  CAS  Google Scholar 

  177. Mathe G, Amiel JL, Schwarzenberg L, et al. Active immunotherapy for acute lymphoblastic leukaemia. Lancet 1969; 1: 697–699.

    PubMed  CAS  Google Scholar 

  178. Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993; 90: 3539–3543.

    PubMed  CAS  Google Scholar 

  179. Tepper RI, Pattengale PK, Leder P. Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 1989; 57: 503–512.

    PubMed  CAS  Google Scholar 

  180. Fearon ER, Pardoll DM, Itaya T, et al. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 1990; 60: 397–403.

    PubMed  CAS  Google Scholar 

  181. Gansbacher B, Bannerji R, Daniels B, Zier K, Cronin K, Gilboa E. Retroviral vector-mediated gamma-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 1990; 50: 7820–7825.

    PubMed  CAS  Google Scholar 

  182. Pardoll DM. Cancer vaccines. Immunol Today 1993; 14: 310–316.

    PubMed  CAS  Google Scholar 

  183. Forni G, Parmiani G, Guarini A, Foa R. Gene transfer in tumor therapy [review]. Ann Oncol 1994; 5: 789–794.

    PubMed  CAS  Google Scholar 

  184. Forni G, Giovarelli M, Cavallo F, et al. Cytokine-induced tumor immunogenicity: from exogenous cytokines to gene therapy [review]. Jlmmunother 1993; 14: 253–257.

    CAS  Google Scholar 

  185. Dunussi-Joannopoulos K, Weinstein HJ, Arceci RI, Croop JM. Gene therapy with B7.1 and GM-CSF vaccines in a murine AML model. J Pediatr Hematol Oncol 1997; 19: 536–540.

    PubMed  CAS  Google Scholar 

  186. Cignetti A, Guarini A, Carbone A, et al. Transduction of the IL2 gene into human acute leukemia cells: induction of tumor rejection without modifying cell proliferation and IL2 receptor expression. J Natl Cancer Inst 1994; 86: 785–791.

    PubMed  CAS  Google Scholar 

  187. Orchard PJ, Katsanis E, Boyer M, May C, Mclvor RS, Blazar BR. Interleukin-2 secretion by transduced and unselected BDL-2 lymphoma results in increased survival in mice with previously established disseminated disease. Cancer Biother Radiopharm 1996; 11: 155–164.

    PubMed  CAS  Google Scholar 

  188. Dilloo D, Bacon K, Holden W, et al. Combined chemokine and cytokine gene transfer enhances antitumor immunity. Nat Med 1996; 2: 1090–1095.

    PubMed  CAS  Google Scholar 

  189. Kopantzev E, Roschke V, Rudikoff S. Interleukin-2-mediated modulation of plasma cell tumor growth in a model of multiple myeloma. Hum Gene Ther 1998; 9: 13–19.

    PubMed  CAS  Google Scholar 

  190. Hsieh CL, Pang VF, Chen DS, Hwang LH. Regression of established mouse leukemia by GM-CSF-transduced tumor vaccine: implications for cytotoxic T lymphocyte responses and tumor burdens. Hum Gene Ther 1997; 8: 1843–1854.

    PubMed  CAS  Google Scholar 

  191. Stewart AK, Schimmer AD, Bailey DJ, et al. In vivo adenoviral-mediated gene transfer of interleukin-2 in cutaneous plasmacytoma. Blood 1998; 91: 1095–1097.

    PubMed  CAS  Google Scholar 

  192. Dunussi-Joannopoulos K, Leonard JP. Interleukin-12 gene therapy vaccines: directing the immune system against minimal residual leukemia. Leukemia Lymphoma 2001; 41: 483–492.

    PubMed  CAS  Google Scholar 

  193. Dunussi-Joannopoulos K, Runyon K, Erickson J, Schaub RG, Hawley RG, Leonard JP. Vaccines with interleukin-12-transduced acute myeloid leukemia cells elicit very potent therapeutic and long-lasting protective immunity. Blood 1999; 94: 4263–4273.

    PubMed  CAS  Google Scholar 

  194. Dunussi-Joannopoulos K, Dranoff G, Weinstein HJ, Ferrara JL, Bierer BE, Croop JM. Gene immunotherapy in murine acute myeloid leukemia: granulocyte-macrophage colony-stimulating factor tumor cell vaccines elicit more potent antitumor immunity compared with B7 family and other cytokine vaccines. Blood 1998; 91: 222–230.

    PubMed  CAS  Google Scholar 

  195. Stripecke R, Skelton DC, Pattengale PK, Shimada H, Kohn DB. Combination of CD80 and granulocyte-macrophage colony-stimulating factor coexpression by a leukemia cell vaccine: preclinical studies in a murine model recapitulating Philadelphia chromosome-positive acute lymphoblastic leukemia. Hum Gene Ther 1999; 10: 2109–2122.

    PubMed  CAS  Google Scholar 

  196. Borrello I, Sotomayor EM, Cooke S, Levitsky HI. A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines. Hum Gene Ther 1999; 10: 1983–1991.

    PubMed  CAS  Google Scholar 

  197. Nelson EL, Li X, Hsu FJ, et al. Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin’s lymphoma. Blood 1996; 88: 580–589.

    PubMed  CAS  Google Scholar 

  198. Steinman RM, Lustig DS, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. 3. Functional properties in vivo. J Exp Med 1974; 139: 1431–1445.

    PubMed  CAS  Google Scholar 

  199. Steinman RM, Adams JC, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. IV. Identification and distribution in mouse spleen. J Exp Med 1975; 141: 804–820.

    PubMed  CAS  Google Scholar 

  200. Baggers J, Ratzinger G, Young JW. Dendritic cells as immunologic adjuvants for the treatment of cancer. J Clin Oncol 2000; 18: 3879–3882.

    PubMed  CAS  Google Scholar 

  201. Ribas A, Butterfield LH, Economou JS. Genetic immunotherapy for cancer. Oncologist 2000; 5: 87–98.

    PubMed  CAS  Google Scholar 

  202. Movassagh M, Baillou C, Cosset FL, Klatzmann D, Guigon M, Lemoine FM. High level of retrovirus-mediated gene transfer into dendritic cells derived from cord blood and mobilized peripheral blood CD34+ cells. Hum Gene Ther 1999; 10: 175–187.

    PubMed  CAS  Google Scholar 

  203. Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2: 52–58.

    PubMed  CAS  Google Scholar 

  204. Mitchell DA, Nair SK. RNA-transfected dendritic cells in cancer immunotherapy. J Clin Invest 2000; 106: 1065–1069.

    PubMed  CAS  Google Scholar 

  205. Westermann J, Kopp J, Korner I, et al. Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia. Bone Marrow Transplant 2000; 25 (suppl 2): S46 - S49.

    PubMed  Google Scholar 

  206. Choudhury BA, Liang JC, Thomas EK, et al. Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses. Blood 1999; 93: 780–786.

    PubMed  CAS  Google Scholar 

  207. Paczesny S, Beranger S, Salzmann JL, Klatzmann D, Colombo BM. Protection of mice against leukemia after vaccination with bone marrow-derived dendritic cells loaded with apoptotic leukemia cells. Cancer Res 2001; 61: 2386–2389.

    PubMed  CAS  Google Scholar 

  208. Shedlock DJ, Weiner DB. DNA vaccination: antigen presentation and the induction of immunity. J Leukoc Biol 2000; 68: 793–806.

    PubMed  CAS  Google Scholar 

  209. Reichardt VL, Okada CY, Liso A, et al. Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma-a feasibility study. Blood 1999; 93: 2411–2419.

    PubMed  CAS  Google Scholar 

  210. He L, Feng H, Raymond A, et al. Dendritic-cell-peptide immunization provides immunoprotection against bcr-abl-positive leukemia in mice. Cancer Immunol Immunother 2001; 50: 31–40.

    PubMed  CAS  Google Scholar 

  211. Rosenberg Sa, Anderson Wf, Blaese M, et al. The development of gene therapy for the treatment of cancer. Ann Surg 1993;218:455–463; discussion 463–464.

    Google Scholar 

  212. Hwu P, Yannelli J, Kriegler M, et al. Functional and molecular characterization of tumor-infiltrating lymphocytes transduced with tumor necrosis factor-alpha cDNA for the gene therapy of cancer in humans. J Immunol 1993; 150: 4104–4115.

    PubMed  CAS  Google Scholar 

  213. Miller J, Tessemer-Tuck J, Blake N, et al. Endogenous IL-2 production by natural killer cells maintains cytotoxic and proliferative capacity following retroviral mediated gene transfer. Exp Hematol 1997; 25: 1140–1148.

    PubMed  CAS  Google Scholar 

  214. Korbelik M, Sun J. Cancer treatment by photodynamic therapy combined with adoptive immunotherapy using genetically altered natural killer cell line. Int J Cancer 2001; 93: 269–274.

    PubMed  CAS  Google Scholar 

  215. Treisman J, Hwu P, Minamoto S, et al. Interleukin-2-transduced lymphocytes grow in an autocrine fashion and remain responsive to antigen. Blood 1995; 85: 139–145.

    PubMed  CAS  Google Scholar 

  216. Tam YK, Klingemann HG. Antileukemic effect of interleukin-2-transduced murine bone marrow after autologous transplantation. Biol Blood Marrow Transplant 1999; 5: 231–242.

    PubMed  CAS  Google Scholar 

  217. Minamoto S, Treisman J, Hankins WD, Sugamura K, Rosenberg SA. Acquired erythropoietin responsiveness of interleukin-2-dependent T lymphocytes retrovirally transduced with genes encoding chimeric erythropoietin/interleukin-2 receptors. Blood 1995; 86: 2281–2287.

    PubMed  CAS  Google Scholar 

  218. Dembic Z, Haas W, Weiss S, et al. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature 1986; 320: 232–238.

    PubMed  CAS  Google Scholar 

  219. Gross G, Gorochov G, Waks T, Eshhar Z. Generation of effector T cells expressing chimeric T cell receptor with antibody type-specificity. Transplant Proc 1989; 21: 127–130.

    PubMed  CAS  Google Scholar 

  220. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci USA 1989; 86: 10024–10028.

    PubMed  CAS  Google Scholar 

  221. Bird RE, Hardman KD, Jacobson JW, et al. Single-chain antigen-binding proteins. Science 1988; 242: 423–426.

    PubMed  CAS  Google Scholar 

  222. Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA 1993; 90: 720–724.

    PubMed  CAS  Google Scholar 

  223. Hwu P, Shafer GE, Treisman J, et al. 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.

    PubMed  CAS  Google Scholar 

  224. Hwu P, Yang JC, Cowherd R, et al. In vivo antitumor activity of T cells redirected with chimeric antibody/T-cell receptor genes. Cancer Res 1995; 55: 3369–3373.

    PubMed  CAS  Google Scholar 

  225. Moritz D, Wels W, Mattem J, Groner B. Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells. Proc Natl Acad Sci USA 1994; 91: 4318–4322.

    PubMed  CAS  Google Scholar 

  226. Altenschmidt U, Klundt E, Groner B. Adoptive transfer of in vitro-targeted, activated T lymphocytes results in total tumor regression. J Immunol 1997; 159: 5509–5515.

    PubMed  CAS  Google Scholar 

  227. Hwu P, Rosenberg SA. The genetic modification of T cells for cancer therapy: an overview of laboratory and clinical trials. Cancer Detect Prey 1994; 18: 43–50.

    CAS  Google Scholar 

  228. Hombach A, Schneider C, Sent D, et al. 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; 88: 115–120.

    PubMed  CAS  Google Scholar 

  229. Jensen MC, Clarke P, Tan G, et al. Human T lymphocyte genetic modification with naked DNA. Mol Ther 2000; 1: 49–55.

    PubMed  CAS  Google Scholar 

  230. Mclvor RS. Drug-resistant dihydrofolate reductases: generation, expression and therapeutic application. Bone Marrow Transplant 1996; 18 (suppl 3): S50 - S54.

    Google Scholar 

  231. James RI, May C, Vagt MD, Studebaker R, Mclvor RS. Transgenic mice expressing the tyr22 variant of murine DHFR: protection of transgenic marrow transplant recipients from lethal doses of methotrexate. Exp Hematol 1997; 25: 1286–1295.

    PubMed  CAS  Google Scholar 

  232. Mclvor RS, Simonsen CC. Isolation and characterization of a variant dihydrofolate reductase cDNA from methotrexate-resistant murine L5178Y cells. Nucleic Acids Res 1990; 18: 7025–7032.

    Google Scholar 

  233. Zhao RC, Mclvor RS, Griffin JD, Verfaillie CM. Gene therapy for chronic myelogenous leukemia (CML): a retroviral vector that renders hematopoietic progenitors methotrexateresistant and CML progenitors functionally normal and nontumorigenic in vivo. Blood 1997; 90: 4687–4698.

    PubMed  CAS  Google Scholar 

  234. Kondratov RV, Komarov PG, Becker Y, Ewenson A, Gudkov AV. Small molecules that dramatically alter multidrug resistance phenotype by modulating the substrate specificity of Pglycoprotein. Proc Natl Acad Sci USA 2001; 98: 14078–14083.

    PubMed  CAS  Google Scholar 

  235. Abonour R, Williams DA, Einhorn L, et al. Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells. Nat Med 2000; 6: 652–658.

    PubMed  CAS  Google Scholar 

  236. Moscow JA, Huang H, Carter C, et al. Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy. Blood 1999; 94: 52–61.

    PubMed  CAS  Google Scholar 

  237. Devereux S, Corney C, Macdonald C, et al. Feasibility of multidrug resistance (MDR-1) gene transfer in patients undergoing high-dose therapy and peripheral blood stem cell transplantation for lymphoma. Gene Ther 1998; 5: 403–408.

    PubMed  CAS  Google Scholar 

  238. Bunting KD, Galipeau J, Topham D, Benaim E, Sorrentino BP. Transduction of murine bone marrow cells with an MDR1 vector enables ex vivo stem cell expansion, but these expanded grafts cause a myeloproliferative syndrome in transplanted mice. Blood 1998; 92: 2269–2279.

    PubMed  CAS  Google Scholar 

  239. Beausejour CM, Eliopoulos N, Momparler L, Le NL, Momparler RL. Selection of drug-resistant transduced cells with cytosine nucleoside analogs using the human cytidine deaminase gene. Cancer Gene Ther 2001; 8: 669–676.

    PubMed  CAS  Google Scholar 

  240. Eliopoulos N, Bovenzi V, Le NL, et al. Retroviral transfer and long-term expression of human cytidine deaminase cDNA in hematopoietic cells following transplantation in mice. Gene Ther 1998; 5: 1545–1551.

    PubMed  CAS  Google Scholar 

  241. Newcomb EW. P53 gene mutations in lymphoid diseases and their possible relevance to drug resistance. Leukemia Lymphoma 1995; 17: 211–221.

    PubMed  CAS  Google Scholar 

  242. Tsai T, Davalath S, Rankin C, et al. Tumor suppressor gene alteration in adult acute lymphoblastic leukemia (ALL). Analysis of retinoblastoma (Rb) and p53 gene expression in lymphoblasts of patients with de novo, relapsed, or refractory ALL treated in Southwest Oncology Group studies. Leukemia 1996; 10: 1901–1910.

    PubMed  CAS  Google Scholar 

  243. Zhou M, Gu L, Yeager AM, Findley HW. Sensitivity to Fas-mediated apoptosis in pediatric acute lymphoblastic leukemia is associated with a mutant p53 phenotype and absence of Bc1–2 expression. Leukemia 1998; 12: 1756–1763.

    PubMed  CAS  Google Scholar 

  244. Bossi G, Scardigli R, Musiani P, et al. Development of a murine orthotopic model of leukemia: evaluation of TP53 gene therapy efficacy. Cancer Gene Ther 2000; 7: 135–143.

    PubMed  CAS  Google Scholar 

  245. Scardigli R, Bossi G, Blandino G, Crescenzi M, Soddu S, Sacchi A. Expression of exogenous wt-p53 does not affect normal hematopoiesis: implications for bone marrow purging. Gene Ther 1997; 4: 1371–1378.

    PubMed  CAS  Google Scholar 

  246. Hirai M, LaFace D, Robinson S, et al. Ex vivo purging by adenoviral p53 gene therapy does not affect NOD-SCID repopulating activity of human CD34+ cells. Cancer Gene Ther 2001; 8: 936–947.

    PubMed  CAS  Google Scholar 

  247. Cotter FE, Johnson P, Hall P, et al. Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. Oncogene 1994; 9: 3049–3055.

    PubMed  CAS  Google Scholar 

  248. Cotter FE, Waters J, Cunningham D Human Bc1–2 antisense therapy for lymphomas. Biochim Biophys Acta 1999; 1489: 97–106.

    PubMed  CAS  Google Scholar 

  249. Motomura S, Motoji T, Takanashi M, et al. Inhibition of P-glycoprotein and recovery of drug sensitivity of human acute leukemic blast cells by multidrug resistance gene (mdrl) antisense oligonucleotides. Blood 1998; 91: 3163–3171.

    PubMed  CAS  Google Scholar 

  250. Zhao RC, Jiang Y, Verfaillie CM. A model of human p210(bcr/ABL)-mediated chronic myelogenous leukemia by transduction of primary normal human CD34(+) cells with a BCR/ABL-containing retroviral vector. Blood 2001; 97: 2406–2412.

    PubMed  CAS  Google Scholar 

  251. Wang Y, Liu J, Wu Y, et al. Expression of a truncated first exon BCR sequence in chronic myelogenous leukemia cells blocks cell growth and induces cell death. Cancer Res 2001; 61: 138–144.

    PubMed  CAS  Google Scholar 

  252. Saggio I, Ciapponi L, Savino R, Ciliberto G, Perricaudet M. Adenovirus-mediated gene transfer of a human IL-6 antagonist. Gene Ther 1997; 4: 839–845.

    PubMed  CAS  Google Scholar 

  253. Phylactou LA. Ribozyme and peptide-nucleic acid-based gene therapy. Adv Drug Deliv Rev 2000; 44: 97–108.

    PubMed  CAS  Google Scholar 

  254. Kuwabara T, Warashina M, Tanabe T, Tani K, Asano S, Taira K. Comparison of the specificities and catalytic activities of hammerhead ribozymes and DNA enzymes with respect to the cleavage of BCR-ABL chimeric L6 (b2a2) mRNA. Nucleic Acids Res 1997; 25: 3074–3081.

    PubMed  CAS  Google Scholar 

  255. Matsushita H, Kizaki M, Kobayashi H, et al. Restoration of retinoid sensitivity by MDR1 ribozymes in retinoic acid-resistant myeloid leukemic cells. Blood 1998; 91: 2452–2458.

    PubMed  CAS  Google Scholar 

  256. Kozu T, Sugio Y, Fukuyama T, Sueoka E, Otsuka T, Akagi K. Ribonuclease H attack of leukaemic fused transcripts AML1–MTG8 (ETO) by DNA/RNA chimeric hammerhead ribozymes. Genes Cells 2000; 5: 637–647.

    PubMed  CAS  Google Scholar 

  257. Suwanai H, Matsushita H, Kobayashi H, Ikeda Y, Kizaki M. A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: improved design of maxizymes against PML/RARalpha rRNA. Int J Oncol 2002; 20: 127–130.

    PubMed  CAS  Google Scholar 

  258. Nason-Burchenal K, Allopenna J, Begue A, Stehelin D, Dmitrovsky E, Martin P. Targeting of PML/RARalpha is lethal to retinoic acid-resistant promyelocytic leukemia cells. Blood 1998; 92: 1758–1767.

    PubMed  CAS  Google Scholar 

  259. Kuwabara T, Hamada M, Warashina M, Taira K. Allosterically controlled single-chained maxizymes with extremely high and specific activity. Biomacromolecules 2001; 2: 788–799.

    PubMed  CAS  Google Scholar 

  260. Kuwabara T, Warashina M, Tanabe T, Tani K, Asano S, Taira K. A novel allosterically trans-activated ribozyme, the maxizyme, with exceptional specificity in vitro and in vivo. Mol Cell 1998; 2: 617–627.

    PubMed  CAS  Google Scholar 

  261. Tanabe T, Kuwabara T, Warashina M, Tani K, Taira K, Asano S. Oncogene inactivation in a mouse model. Nature 2000; 406: 473–474.

    PubMed  CAS  Google Scholar 

  262. Zwacka RM, Dunlop MG. Gene therapy for colon cancer. Hematol Oncol Clin North Am 1998; 12: 595–615.

    PubMed  CAS  Google Scholar 

  263. Kunishige I, Samejima Y, Shiki Y, et al. Suicide gene therapy for human uterine adenocarcinoma cells using herpes simplex virus thymidine kinase. Gynecol Oncol 1999; 72: 16–25.

    PubMed  CAS  Google Scholar 

  264. Yamamoto S, Suzuki S, Hoshino A, Akimoto M, Shimada T. Herpes simplex virus thymidine kinase/ganciclovir-mediated killing of tumor cells induces tumor-specific cytotoxic t cells in mice. Cancer Gene Ther 1997; 4: 91–96.

    PubMed  Google Scholar 

  265. Klatzmann D. Gene therapy for metastatic malignant melanoma: evaluation of tolerance to intratumoral injection of cells producing recombinant retroviruses carrying the herpes simplex virus type 1 thymidine kinase gene, to be followed by ganciclovir administration. Hum Gene Ther 1996; 7: 255–667.

    PubMed  CAS  Google Scholar 

  266. Tiberghien P, Reynolds CW, Keller J, et al. Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation Blood 1994; 84: 1333–1341.

    PubMed  CAS  Google Scholar 

  267. Bordignon C, Bonini C, Verzeletti S, et al. Transfer of the hsv-tk gene into donor peripheral blood lymphocytes for in vivo modulation of donor anti-tumor immunity after allogeneic bone marrow transplantation. Hum Gene Ther 1995; 6: 813–819.

    PubMed  CAS  Google Scholar 

  268. Gale RP, Horowitz MM. Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant 1990; 6 (suppl 1): 94–97.

    PubMed  Google Scholar 

  269. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    PubMed  CAS  Google Scholar 

  270. Tiberghien P, Cahn JY, Brion A, et al. Use of donor t-lymphocytes expressing herpes-simplex thymidine kinase in allogeneic bone marrow transplantation-a phase i-ii study. Hum Gene Ther 1997; 8: 615–624.

    PubMed  CAS  Google Scholar 

  271. Bonini C, Ferrari G, Verzeletti S, et al. Hsv-tk gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997; 276: 1719–1724.

    PubMed  CAS  Google Scholar 

  272. Cohen IL, Boyer O, Salomon B, et al. Prevention of graft-versus-host disease in mice using a suicide gene expressed in T lymphocytes. Blood 1997; 89: 4636–4645.

    PubMed  CAS  Google Scholar 

  273. Contassot E, Ferrand C, Angonin R, et al. Ganciclovir-sensitive acute graft-versus-host disease in mice receiving herpes simplex virus-thymidine kinase-expressing donor T cells in a bone marrow transplantation setting. Transplantation 2000; 69: 503–508.

    PubMed  CAS  Google Scholar 

  274. Tiberghien P. Use of suicide gene-expressing donor T-cells to control alloreactivity after haematopoietic stem cell transplantation. J Intern Med 2001; 249: 369–377.

    PubMed  CAS  Google Scholar 

  275. Riddell SR, Elliott M, Lewinsohn DA, et al. T-cell mediated rejection of gene-modified hivspecific cytotoxic t lymphocytes in hiv-infected patients. Nat Med 1996; 2: 216–223.

    PubMed  CAS  Google Scholar 

  276. Haberkorn U, Oberdorfer F, Gebert J, et al. Monitoring gene therapy with cytosine deaminase: in vitro studies using tritiated-5-fluorocytosine. J Nucl Med 1996; 37: 87–94.

    PubMed  CAS  Google Scholar 

  277. Mullen CA, Kilstrup M, Blaese RM. Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system. Proc Natl Acad Sci USA 1992; 89: 33–37.

    PubMed  CAS  Google Scholar 

  278. Amara JF, Courage NL, Gilman M Cell surface tagging and a suicide mechanism in a single chimeric human protein. Human Gene Ther 1999; 10: 2651–2655.

    CAS  Google Scholar 

  279. Thomis DC, Marktel S, Bonini C, et al. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease. Blood 2001; 97: 1249–1257.

    PubMed  CAS  Google Scholar 

  280. Beltinger C, Uckert W, Debatin KM. Suicide gene therapy for pediatric tumors. J Mol Med 2001; 78: 598–612.

    PubMed  CAS  Google Scholar 

  281. Greco O, Dachs GU. Gene directed enzyme/prodrug therapy of cancer: historical appraisal and future prospectives. J Cell Physiol 2001; 187: 22–36.

    PubMed  CAS  Google Scholar 

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Authors
  1. Paul J. Orchard MD
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  2. R. Scott Mclvor PhD
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  1. Leukemia Program, Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA

    Matt Kalaycio MD

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Orchard, P.J., Mclvor, R.S. (2003). Gene Therapy. In: Kalaycio, M. (eds) Biologic Therapy of Leukemia. Contemporary Hematology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-383-5_14

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  • DOI: https://doi.org/10.1007/978-1-59259-383-5_14

  • Publisher Name: Humana Press, Totowa, NJ

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