Gene marking and gene therapy directed at primary hematopoietic cells

Current Opinion in Hematology

Volumn 3, Issue 6, 1996, Pages 430-437

  Dunbar, Cynthia E ^a   Young, Neal S ^a  

^a NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CELL SELECTION; CLINICAL TRIAL; CLONING VECTOR; COMBINED IMMUNODEFICIENCY; GENE TARGETING; GENE THERAPY; GENE TRANSFER; GENETIC TRANSDUCTION; HEMATOPOIETIC STEM CELL; HUMAN; IMMUNE RESPONSE; MARKER GENE; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE SUBPOPULATION; TRANSGENE;

EID: 0029857382     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/00062752-199603060-00006     Document Type: Article

References (75)

1. Orkin SH, Motulsky AG: Report and recommendations of the panel to assess the NIH investment in research on gene therapy. Dec. 7, 1995. NIH website (http://www.nih.gov/news/panelrep.html). Report commissioned by the Director of the National Institutes of Health from a panel of experts to assess the current status of laboratory and clinical investigations into gene therapy. They concluded that although many of the clinical trials were premature and likely had no therapeutic benefit, genetic marking trials had provided important information. They recommended refocusing on the basic science of new vector systems, basic biology of target cells, and investigation of mechanisms for diminishing transgene expression.
2. Williams RS: Human gene therapy: of tortoises and hares. Nature Med 1995, 1:1137-1138.
3. Freidmann T: Human gene therapy: an immature genie but certainly out of the bottle. Nature Med 1996, 2:144-147.
4. Leiden JM: Gene therapy: promise, pitfalls, and prognosis. N Engl J Med 1995, 333:871-873.
5. Blaese RM, Culver KW, Miller AD, Carter CS, Fleisher T, Cleric M, Shearer G, Chang L, Chiang Y, Tolstoshev P, et al.: T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science 1995, 270:475-480. The long-awaited 4-year follow-up data from two children with ADA-deficient SCID treated with multiple infusions of autologous lymphocytes transduced with a retroviral vector containing the ADA gene. Both children have fared well clinically, showing improved objective measures of immune function, but the discrepancy between the level of circulating lymphocytes containing the transferred gene in the two patients (> 30% versus < 1%) makes interpretation of the role of gene "therapy" difficult.
6. Bordignon C, Notarangelo LD, Nobili N, Ferrari G, Casorati G, Panina P, Mazzolari E, Maggioni D, Rossi C, Servida P, Ugazio AG, Mavilio F: Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients. Science 1995, 270:470-475. This provocative study used two different ADA gene-containing retroviral vectors to transduce either T cells or bone marrow mononuclear cells from two patients with ADA-deficient SCID. These cells were then reinfused without ablation multiple times in each patient. Of note, early after the infusions the corrected T cells primarily originated from the transduced T cells, but after 1 year, T cells containing the vector began to be derived from the transduced bone marrow cells instead, implying that bone marrow stem cells had been transduced and could eventually contribute to a potentially more normal immune repertoire. Both patients showed clinical improvement, and had more normal patterns of T-cell receptor gene usage patterns over time following the infusions.
7. + compartment than in circulating mature myeloid or lymphoid cell populations. No adverse clinical events occurred, all three children were doing well clinically and beginning to have their exogenous enzyme replacement tapered in order to test for a selective advantage for transduced cells.
8. Dunbar CE, Cottler-Fox M, O'Shaughnessy JA, Doren S, Carter CS, Berenson R, Brown S, Moen RC, Greenblatt J, Stewart FM, et al.: Retrovirally marked CD34-enriched peripheral blood and bone marrow and cells contribute to long-term engraftment after autologous transplantation. Blood 1995, 85:3048-3057. A genetic marking study using two vectors to transduce CD34-enriched mobilized peripheral blood versus bone marrow cells in adult patients undergoing autologous transplantation for myeloma or breast cancer. Cells were transduced with the vectors for 72 hours in the presence of cytokines. Long-term marking of cells from all lineages was demonstrated in some patients, but at levels of only 0.1% or less after the first 3 months. Both the peripheral blood and marrow grafts contributed to the marking, implying that peripheral blood cells can participate in long-term engraftment of multiple lineages.
9. Brenner MK, Rill DR, Holladay MS, Heslop HE, Moen RC, Buschle M, Krance RA, Santana VM, Anderson WF, Ihle JN: Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients. Lancet 1993, 342:1134-1137.
10. Rooney CM, Smith CA, Ng CYC, Loftin S, Li C, Krance RA, Brenner MK, Heslop HE: Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet 1995, 345:9-13.
11. Heslop HE, Ng CYC, Li C, Smith CA, Loftin SK, Krance RA, Brenner MK, Rooney CM: Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nature Med 1996, 2:551-555. Detailed study of gene-marked Epstein-Barr virus-specific T-lymphocyte infusions in patients after allogeneic bone marrow transplantation. The great majority of patients had detectable marked cells present 1 month after infusion, but the marker gene was no longer detectable in the peripheral blood at longer than 4 to 5 months after infusion. However, either in vitro or in vivo challenge with Epstein-Barr virus resulted in expansion of the Epstein-Barr virus-specific, gene-marked cells, indicating long-term persistence of these cells, and a functional capacity to respond to the appropriate stimulation.
12. Xu L, Blanco M, Kluepfel-Stahl S, Dunbar C, Karlsson S: Growth factors and stromal support generate very efficient retroviral transduction of peripheral blood CD34+ cells from Gaucher patients. Blood 1995, 86:141-146.
13. Crooks GM, Kohn DB: Growth factors increase amphotropic retrovirus binding to human CD34+ bone marrow progenitor cells. Blood 1993, 82:3290-3297.
14. van Beusechem VW, Valerio D: Gene transfer into hematopoietic stem cells of nonhuman primates. Hum Gene Ther 1996, in press.
15. Bock TA, Orlic D, Dunbar CE, Broxmeyer HE, Bodine DM: Improved engraftment of human hematopoietic cells in severe combined immune-deficient (SCID) mice carrying human cytokine transgenes. J Exp Med 1995, 182:2037-2043.
16. Nolta JA, Handley MB, Kohn DB: Sustained human hemotopoiesis in immunodeficient mice by cotransplantation of marrow stroma expressing human interleukin-3: analysis of gene transduction of long-lived progenitors. Blood 1994, 83:3041-3051.
17. Dick JE, Kamel-Reid S, Murdoch B, Doedens M: Gene transfer into normal human hematopoietic cells using in vitro and in vivo assays. Blood 1991, 78:624-634.
18. Dick JE: Immune-deficient mice as models of normal and leukemic human hematopoiesis. Cancer Cells 1991, 3:39-48.
19. Nolta JA, Dao MA, Wells S, Smogorzewska EM, Kohn DB: Transduction of pluripotent human hematopoietic stem cells demonstrated by clonal analysis after engraftment in immune deficient mice. Proc Natl Acad Sci U S A 1996, 93:2414-2419. Elegant demonstration of transduction of pluripotent human hematopoietic cells via retroviral integration site analysis of individual human myeloid colony-forming cells and T-cell clones from immunodeficient mice engrafted with transduced human marrow cells at least 9 months previously. Inverse PCR and then sequencing of the resultant product was used to show that in at least three instances, individual T-cell clones and myeloid colonies contained the provirus at the same insertion site, implying common origin from a shared precursor.
20. Nolta JA, Smogorzewska EM, Kohn DB: Analysis of optimal conditions for retroviral-mediated transduction of primitive human hematopoietic cells. Blood 1995, 86:101-105. Use of an immunodeficient mouse xenograft model to compare the effect of different transduction conditions on overall sustained engraftment with human bone marrow or peripheral blood cells as well as the percentage of the human cells containing the vector long-term (more than 9 months). The use of an autologous stromal support layer during transduction was necessary to allow sustained human cell engraftment as well as to improve the percentage of engrafted human cells containing the vector. The addition of the cytokines interleukin-3, interleukin-6, and stem cell factor along with stromal cells during transduction improved the overall gene transfer efficiency to the human marrow but not to peripheral blood cells.
21. Bodine DM, Seidel NE, Zsebo KM, Orlic D: In vivo administration of stem cell factor to mice increases the absolute number of pluripotent hematopoietic stem cells. Blood 1993, 82:445-455.
22. Li CL, Johnson GR: Stem cell factor enhances the survival but not the self-renewal of murine hematopoietic long-term repopulating cells. Blood 1994, 84:408-414.
23. Spangrude GJ, Brooks DM, Tumas DB: Long-term repopulation of irradiated mice with limiting numbers of purified hematopoietic stem cells: in vivo expansion of stem cell phenotype but not function. Blood 1995, 85:1006-1016.
24. Peters SO, Kittler ELW, Ramshaw HS, Quesenberry PJ: Murine marrow cells expanded In culture with IL-3, IL-6, IL-11, and SCF acquire an engraftment defect in normal hosts. Exp Hematol 1995, 23:461-466.
25. van der Loo JCM, Ploemacher RE: Marrow and spleen-seeding efficiencies of all murine hematopoietic stem cell subsets are decreased by preincubation with hematopoietic growth factors. Blood 1995, 85:2598-2606.
26. Schiffmann R, Medin JA, Ward JM, Stahl S, Cottier-Fox M, Karlsson S: Transfer of the human glucocerebrosidase gene into hematopoietic stem cells of nonablated recipients: successful engraftment and long-term expression of the transgene. Blood 1995, 86:1218-1227.
27. Barquinero J, Kiem HP, von Kalle C, Darovsky B, Goehle S, Graham T, Seidel K, Storb R, Schuening FG: Myelosuppressive conditioning improves autologous engraftment of genetically marked hematopoietic repopulating cells in dogs. Blood 1995, 85:1195-1201.
28. Bienzle D, Abrams-Ogg ACG, Kruth SA, Ackland-Snow J, Cater RF, Dick JE, Jacobs RM, Kamel-Reid S, Dubé ID: Gene transfer into hematopoietic stem cells: long-term maintenance of in vitro activated progenitors without marrow ablation. Proc Natl Acad Sci U S A 1994, 91:350-354.
29. Stewart AK, Dube ID, Kamel-Reid S, Keating A: A phase I study of autologous bone marrow transplantation with stem cell gene marking in multiple myeloma. Hum Gene Ther 1995, 6:107-119.
30. Williams DA: Ex-vivo expansion of hematopoietic stem and progenitor cells: robbing Peter to pay Paul? Blood 1993, 81:3169.
31. Emerson SG: Ex vivo expansion of hematopoietic precursors, progenitors, and stem cells: the next generation of cellular therapeutics. Blood 1996, 87:3082-3088.
32. Brugger W, Mocklin W, Heimfeld S, Berenson RJ, Mertelsmann R, Kanz L: Ex vivo expansion of enriched peripheral blood CD34+ progenitor cells by stem cell factor, interleukin 1β (IL-1β), IL-6, IL-3, interferon-γ and erythropoietin. Blood 1993, 81:2579-2584.
33. Koller MR, Emerson SG, Palsson BO: Large-scales expansion of human stem and progenitor cells from bone marrow mononuclear cells in continuous perfusion cultures. Blood 1993, 82:378-384.
34. Petzer AL, Hogge DE, Lansdorp PM, Reid DS, Eaves CJ: Self-renewal of primitive human hematopoietic cells (long-term-culture-initiating cells) in vitro and their expansion in defined medium. Proc Natl Acad Sci U S A 1996, 93:1470-1474.
35. Brugger W, Heimfeld S, Berenson RJ, Mertelsmann R, Kanz L: Reconstitution of hematopoiesis after high-dose chemotherapy by autologous progenitor cells generated ex vivo. N Engl J Med 1995, 333:283-287.
36. Ohishi K, Katayama N, Itoh R, Mahmud N, Miwa H, Kita K, Minami N, Shirakawa S, Lyman SD, Shiku H: Accelerated cell-cycling of hematopoietic progenitors by the flt3 ligand that is modulated by transforming growth factor-β. Blood 1996, 87:1718-1727.
37. Shah AJ, Smogorzweska EM, Hannum C, Crooks GM: Flt3 ligand induces proliferation of quiescent human bone marrow CD34+CD38-cells and maintains progenitor cells in vitro. Blood 1996, 87:3563-3570.
38. Rusten LS, Lyman SD, Veiby OP, Jacobsen SEW: The FLT3 ligand is a direct and potent stimulator of the growth of primitive and committed human CD34+ bone marrow progenitor cells in vitro. Blood 1996, 87:1317-1325.
39. Soma T, Yu JM, Dunbar CE: Maintenance of murine long-term repopulating stem cells in ex vivo culture is affected by modulation of transforming growth factor-β but not macrophage inflammatory protein-1α activities. Blood 1996, 87:4561-4567.
40. Hatzfeld A, Batard P, Panterne B, Taieb F, Hatzfeld J: Increased stable retroviral gene transfer in early hematopoietic progenitors released from quiescence. Hum Gene Ther 1996, 7:207-213.
41. Helgason CD, Sauvageau G, Lawrence HJ, Largman C, Humphries RK: Overexpression of HOXB4 enhances the hematopoietic potential of embryonic stem cells differentiated in vitro. Blood 1996, 87:2740-2749.
42. Sauvageau G, Thorsteindottir U, Eaves CJ, Lawrence HJ, Largman C, Lansdorp PM, Humphries RK: Overexpression of HOXB4 in hematopoietic cells causes the selective expansion of more primitive populations in vitro and in vivo. Genes Devel 1995, 9:1753-1765.
43. Mavilio F, Ferrari G, Rossini S, Nobili N, Bonini C, Casorati G, Traversari C, Bordignon C: Peripheral blood lymphocytes as target cells of retroviral vector-mediated gene transfer. Blood 1994, 83:1988-1997.
44. Pawliuk R, Kay R, Lansdorp P, Humphries RK: Selection of retrovirally transduced hematopoietic cells using CD24 as a marker of gene transfer. Blood 1994, 84:2868-2877.
45. Conneally E, Bardy P, Eaves CJ, Thomas T, Chappel S, Shpall EJ, Humphries RK: Rapid and efficient selection of human hematopoietic cells expressing murine heat-stable antigen as an indicator of retroviral mediated gene transfer. Blood 1996, 87:456-464.
46. Medin JA, Migita M, Pawliuk R, Jacobson S, Amiri M, Kluepfel Stahl S, Brady RO, Humphries RK, Karlsson S: A bicistronic therapeutic retroviral vector enables sorting of transduced CD34+ cells and corrects the enzyme deficiency in cells from Gaucher patients. Blood 1996, 87:1754-1762.
47. Anderson SM, Yu G, Giattina M, Miller JL: Intercellular transfer of a glycosylphosphatidylinositol (GPI)-linked protein: release and uptake of CD4-GPI from recombinant adeno-associated virus-transduced HeLa cells. Proc Natl Acad Sci U S A 1996, 93:5894-5898.
48. Tumas DB, Spangrude GJ, Brooks DM, Williams CD, Chesebro B: High-frequency cell surface expression of a foreign protein in murine hematopoietic stem cells using a new retroviral vector. Blood 1996, 87:509-517.
49. Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC: Green fluorescent protein as a marker for gene expression. Science 1994, 263:802-805.
50. Cheng L, Fu J, Tsukamoto A, Hawley RQ: Use of green fluorescent protein variants to monitor gene transfer and expression in mammalian cells. Nature Biotechnol 1996, 14:606-704.
51. Sorrentino BP, McDonagh KT, Woods D, Orlic D: Expression of retroviral vectors containing the human multidrug resistance 1 cDNA in hematopoietic cells of transplanted mice. Blood 1995, 86:491-501.
52. Jelinek J, Fairbairn LJ, Dexter TM, Rafferty JA, Stocking C, Ostertag W, Margison GP: Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase. Blood 1996, 87:1957-1961.
53. Spencer HT, Sleep SEH, Rehg JE, Blakley RL, Sorrentino B: A gene transfer strategy for making bone marrow cells resistant to trimetrexate. Blood 1996, 87:2579-2587.
54. Jonsson JJ, Habel DE, McIvor RS: Retrovirus-mediated transduction of an engineered intron-containing purine nucleoside phosphorylase gene. Hum Gene Ther 1995, 6:611-623.
55. Dai Y, Schwarz EM, Gu D, Zhang WW, Sarvetnick N, Verma IM: Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: tolerization of factor IX and vector antigens allows for long-term expression. Proc Natl Acad Sci U S A 1995, 92:1401-1405.
56. Yang Y, Li Q, Ertl HC, Wilson JM: Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol 1995, 69:2004-2015.
57. Koenig S: A lesson from the HIV patient: the immune response is still the bane (or promise) of gene therapy. Nature Med 1996, 2:165-167.
58. Rabinovich NR, McInnes P, Klein DL, Hall BF: Vaccine technologies: view to the future. Science 1994, 265:1401-1404.
59. Sykes M, Sachs DH, Nienhuis AW, Pearson DA, Moulton AD, Bodine DM: Specific prolongation of skin graft survival following retroviral transduction of bone marrow with an allogeneic major histocompatibility complex gene. Transplantation 1993, 55:197-202.
60. LeGuern C, Shimada H, Emery DW, Germana S, Shafer GE, Sachs DH: Retrovirus-mediated transfer of MHC class II cDNA into swine bone marrow cells. J Mol Med 1995, 73:269-278.
61. Riddell SR, Elliott M, Lewinsohn DA, Gilbert MJ, Wilson L, Manley SA, Lupton SD, Overell RW, Reynolds TC, Corey L, Greenberg PD: T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nature Med 1996, 2:216-223. Convincing and very concerning demonstration of antitransgene-specific cell-mediated immunity developing in HIV-positive patients receiving repeated infusions of retrovirally transduced autologous HIV-specific cytotoxic T cells. The development of these immune responses correlated with the disappearance of the vector-containing lymphocytes, suggesting that antitransgene immune responses may preclude this approach to genetic therapy, even in immunosuppressed patients.
62. Tripathy SK, Black HB, Goldwasser E, Leiden JM: Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nature Med 1996, 2:545-550. Demonstration of specific antitransgene immune responses in mice injected intramuscularly with adenoviral vectors expressing human erythropoietin that were not seen in mice receiving vectors expressing murine erythropoietin or no exogenous gene. Disappearance of detectable erythropoietin in the circulation correlated with disappearance of vector-containing cells. These mice eventually became anemic and could be shown to have developed an immune response against endogenous murine erythropoietin as well. Mice receiving adenoviral injections of recombinant vectors expressing the murine erythropoietin gene had sustained elevations in hematocrit and no loss of transduced cells on muscle biopsy, suggesting that an antitransgene humoral and cellular immune response was more physiologically important that an antiadenoviral response.
63. Yang Y, Trinchieri G, Wilson JM: Recombinant IL-12 prevents formation of blocking IgA antibodies to recombinant adenovirus and allows repeated gene therapy to mouse lung. Nature Med 1995, 1:890-893.
64. Cosset FL, Morling FJ, Takeuchi Y, Weiss RA, Collins MKL, Russell SJ: Retroviral retargeting by envelopes expressing an N-terminal binding domain. J Virol 1995, 69:6314-6322. Demonstration that targeting via introduction of new sequences into the murine Moloney virus ecotropic envelope gene allows receptor-specific binding but may not allow appropriate internalization and trafficking, leading to successful integration. Insertion of amphotropic receptor binding sequences did allow transduction of human cells by an ecotropic-derived envelope, but epidermal growth factor sequences inserted in the same position allowed binding to epidermal growth factor receptor-positive human cells but no transduction or integration.
65. Somia NV, Zoppe M, Verma IM: Generation of targeted retroviral vectors by using single-chain variable fragment: an approach to in vivo gene delivery. Proc Natl Acad Sci U S A 1995, 92:7570-7574.
66. Schwarzenberger P, Spence SE, Gooya JM, Michiel D, Curiel DT, Ruscetti FW, Keller JR: Targeted gene transfer to human hematopoietic progenitor cell lines through the c-kit receptor. Blood 1996, 87:472-478.
67. Yang Y, Vanin EF, Whitt MA, Fornerod M, Zwart R, Schneiderman RD, Grosweld G, Nienhuis AW: Inducible, high-level production of infectious murine leukemia retroviral vector particles pseudotyped with vesicular stomatitis virus G envelope protein. Hum Gene Ther 1995, 6:1203-1213.
68. von Kalle C, Kiem HP, Goehle S, Darovsky B, Heimfeld S, Torok Storb B, Storb R, Schuening FG: Increased gene transfer into human hematopoietic progenitor cells by extended in vitro exposure to a pseudotyped retroviral vector. Blood 1995, 84:2890-2897.
69. Bunnell BA, Muul LM, Donahue RE, Blaese RM, Morgan RA: High-efficiency retroviral-mediated gene transfer into human and nonhuman primate peripheral blood lymphocytes. Proc Natl Acad Sci U S A 1995, 92:7739-7743.
70. Chuck AS, Palsson BO: Consistent and high rates of gene transfer can be obtained using flow-through transduction over a wide range of retroviral titers. Hum Gene Ther 1996, 7:743-750. Novel approach to increasing the likelihood of interaction between a retroviral vector particle and its target cell. Performing transductions by flowing retroviral vector-containing supernatant through a filter trapping the target cells greatly improved transduction efficiency of cell lines and primary hematopoietic cells and basically negated the need for high-titer vector supernatants.
71. Naldini L, Blömer U, Gallay P, Ory D, Mulligan R, Gage F, Verma IM, Trono D: In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 1996, 272:263-267. A preliminary study of the possible use of an HIV-based vector system to generate vectors that appear to successfully transduce nondividing cell populations. These vectors appear to have a prolonged stable half-life inside cells, allowing more prolonged opportunities for integration and gene expression even without integration.
72. Yu SF, Baldwin DN, Gwynn SR, Yendapalli S, Linial ML: Human foamy virus replication: a pathway distinct from that of retroviruses and hepandnaviruses. Science 1996, 271:1579-1582.
73. Russell DW, Miller AD: Foamy virus vectors. J Virol 1996, 70:217-222.
74. Russell DW, Alexander IE, Miller AD: DNA synthesis and topoisomerase inhibitors increase transduction by adeno-associated virus vectors. Proc Natl Acad Sci U S A 1995, 92:5719-5723.
75. Tamayose K, Hirai Y, Shimada T: A new strategy for large-scale preparation of high-titer recombinant adeno-associated virus vectors by using packaging cell lines and sulfonated cellulose column chromatography. Hum Gene Ther 1996, 7:507-513.