Skip to main content
SpringerLink
Log in

The Role of the Blood Bank in Human Gene Therapy Trials

  • Chapter
Hereditary Diseases and Blood Transfusion

Part of the book series: Developments in Hematology and Immunology ((DIHI,volume 30))

  • 40 Accesses

Abstract

Molecular biology has developed over the last two decades as the structure and function of many genes and their regulation have begun to be elucidated. This basic understanding of gene expression in cells led to studies to genetically transfer genes into cells. Initial studies in gene transfer for gene therapy purposes focused on diseases in which the gene of interest is mutated and thus led to treatment of a genetic disease resulting from the dysfunction of a single gene (e.g., Lesch-Nyhan Syndrome) [1,2]. The mutated gene leads to a dysfunctional protein or unexpressed gene. The early studies for gene therapy focused on these genetic diseases since it was hypothesized that replacing a single gene defect would be the easiest and most ethical approach to the first clinical gene therapy trial [3]. In order to genetically modify a renewable population of cells so that the gene would be expressed for the lifetime of an individual, gene transfer into haematopoietic stem cells to correct a lymphocyte defect, adenosine deaminase deficiency (ADA), seemed the most likely approach. Currently, there are six main groups of target diseases for stem cell gene transfer. Disease affecting red blood cells, such as sickle cell anaemia and thalassaemia, could be cured by insertion of a normal globin gene into stem cells. Neutrophil deficiencies that are caused by an enzyme defect (e.g., chronic granulomatous disease) lead to chronic infections, and can be corrected by insertion of the normal gene that corrects the oxidative pathway [4]. Storage disease can be corrected through stem cell gene transfer, which would correct the genetic defect within the monocyte cell population.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Edwards NL, Jeryc W, Fox IH. Enzyme replacement in the Lesch-Nyhan syndrome with long-term erythrocyte transfusions. Adv Exp Med Biol 1984;165A:23–26.

    Google Scholar 

  2. Dick JE, Magli MC, Huszar D, Philips RA, Bernstein A. Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/Wv mice. Cell 1985;42:71–79.

    Article  PubMed  CAS  Google Scholar 

  3. Karlsson S. Treatment of genetic defects in hematopoietic cell function by gene therapy. Blood 1991;78:2481–92.

    PubMed  CAS  Google Scholar 

  4. Cobb CS, Malech HL, Leto TL, et al. Retrovial mediated restoration of p47phox protein to EBV-transformed B lymphocytes from a patient with chronic granulomatous disease. Blood 1992;79:1829–35.

    Google Scholar 

  5. Sullenger BA, Gallardo HF, Ungers GE, Gilboa E. Overexpression of TAR sequences renders cells resistant to human immunodficiency virus replication. Cell 1990;63: 601–8.

    Article  PubMed  CAS  Google Scholar 

  6. Freeman SM, Zwiebel JA. Gene therapy of cancer. Cancer Invest 1993;11:676–88.

    Article  PubMed  CAS  Google Scholar 

  7. Mann R, Mulligen RC, Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 1983;33:153–59.

    Article  PubMed  CAS  Google Scholar 

  8. Miller AD, Law MF, Verma IM. Generation of helper-free amphotropic retroviruses thattransduceadominant-acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol 1985;5:431–37.

    PubMed  CAS  Google Scholar 

  9. Cone RD, Mulligan RC. High-efficiency gene transfer into mammalian cells: Generation of helper-free recombinant retrovirus with broad mammalian host gene. Proc Natl Acad Sci USA 1984:6349–53.

    Google Scholar 

  10. Sorrentino BP, Brandt SJ, Bodine D, et al. Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR-1. Science 1992;257:99–103.

    Article  PubMed  CAS  Google Scholar 

  11. Linial ML, Miller AD. Retroviral RNA packaging: Sequence requirements and implications. Curr Top Microbiol Immunol 1990;157:125–52.

    Article  PubMed  CAS  Google Scholar 

  12. Scharfmann R, Axelrod JH, Verma IM. Long term in vivo expression of retroviral-mediated gene transfer in mouse fibroblast implants. Proc Natl. Acad Sci USA 1991;88:4626–30.

    Article  PubMed  CAS  Google Scholar 

  13. Correll PH, Colilla S, Karlsson S. Retroviral vector design for long-term expression in murine hematopoietic cells in vivo. Blood 1994;84:1812–22.

    PubMed  CAS  Google Scholar 

  14. Kaleko M, Garcia JV, Osborn WRA, Miller AD. Expression of human adenosine deaminase in mice after transplantation of genetically-modified bone marrow. Blood 1990;75:1733.

    PubMed  CAS  Google Scholar 

  15. Yu-SF, von Ruden T, Kantoff PW, et al. Self-inactivating retroviral vectors designed for transfer of whole genes into mammalian cells. Proc Natl Acad Sci USA 1986;83: 3194–98.

    Article  Google Scholar 

  16. Guild BC, Finer MH, Houseman DE, Mulligan RC. Development of retrovirus vectors useful for expressing genes in cultured murine embryonal cells and hematopoietic cells in vivo J Virol 1988;62:3795–3806.

    PubMed  CAS  Google Scholar 

  17. Miller DG, Adam MA, Miller AD. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 1990; 10: 4239–42.

    PubMed  CAS  Google Scholar 

  18. Springett GM, Moen RC, Anderson S, Blaese RM, Anderson WF. Infection efficiency of T lymphocytes with amphotropic retroviral vectors is cell cycle dependent. J Virol 1989;63:3865–69.

    PubMed  CAS  Google Scholar 

  19. Hermonat PL, Muzyczka. Use of adeno-associated virus as a mammalian DNA cloning vector: Transduction of neomycin resistance into mammalian tissue culture cells. Proc Natl Acad Sci USA 1984;81:6466–70.

    Article  PubMed  CAS  Google Scholar 

  20. Kotin RM, Siniscalo M, Samulski RJ, et al. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 1990;87:211–15.

    Article  Google Scholar 

  21. Walsh CE, Liu JM, Young N, Xiao X, Nienhuis AW, Samulski RJ. Regulated high level expression of a human g-globin gene introduced into erythroid cells by a novel adeno-associated virus (AAV) vector. Proc Natl Acad Sci USA 1992;89:7257–61.

    Article  PubMed  CAS  Google Scholar 

  22. Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science 1988;24:58–62.

    Article  Google Scholar 

  23. Correl PH, Kew Y, Perry LK, Brady RO, Fink JK, Karlsson S. Expression of human glucocerebrosidase in long-term reconstituted mice following retroviral-mediated gene transfer into hematopoietic stem cells. Hum Gene Ther 1990;1:277–87.

    Article  Google Scholar 

  24. Craig JI, Turner ML, Parker AC. Peripheral blood stem cell transplantation. Blood Rev 1992;6:59–67.

    Article  PubMed  CAS  Google Scholar 

  25. Bodine DM, Karlsson S, Nienhuis AW. Combination of IL-3 and IL-6 preserves stem cell function in culture and enhances retrovirus-mediated gene transfer into hematopoietic stem cells. Proc Natl Acad Sci USA 1989;86:8897–8901.

    Article  PubMed  CAS  Google Scholar 

  26. Hogge DE, Humpries RK. Gene transfer to primary normal human hematopoietic progenitor cells using recombinant retroviruses. Blood 1987;69:611–17.

    PubMed  CAS  Google Scholar 

  27. Dexter TM, Allen TD, Lajtha LG. Conditions controlling the proliferation of hemopoietic stem cells in vitro. J Cell Physiol 1977;91:335–44.

    Article  PubMed  CAS  Google Scholar 

  28. Abraham NG, Chertkov JL, Staudinger R, et al. Long-term bone marrow stromal and hemopoietic toxicity to AZT: Protective role of heme and IL-1. Exp Hematol 1993; 21:263–68.

    PubMed  CAS  Google Scholar 

  29. Chertkov JL, Drize NJ, Gurevitch OA, Udalov GA. Cells responsible for restoration of hemopoiesis in long-term murine bone marrow culture. Leuk Res 1986;10:659–65.

    Article  PubMed  CAS  Google Scholar 

  30. Apperley JF, Williams DA. Gene therapy: Current status and future directions. Br J Haematol 1990;75:148–55.

    Article  PubMed  CAS  Google Scholar 

  31. Williams DA. Expression of introduced genetic sequences in hematopoietic cells following retroviral-mediated gene transfer. Human Gene Ther 1990;1:229–39.

    Article  CAS  Google Scholar 

  32. Moritz T, Platel VP, Williams DA. Bone marrow extracellular matrix molecules improve gene transfer into human hematopoietic cells via retroviral vectors. J Clin Invest 1994;93:1451–57.

    Article  PubMed  CAS  Google Scholar 

  33. Luskey BD, Rosenblatt M, Zsebo K, Williams DA. Stem cell factor, IL-3 and IL-6 promote retroviral mediated gene transfer into murine hematopoietic stem cells. Blood 1992;80:396–402.

    PubMed  CAS  Google Scholar 

  34. Moore KA, Deisseroth AB, Reading CL, Williams DE, Belmont JW. Stromal support enhances cell-free retroviral vector transduction of human bone marrow long term initiating cells. Blood 1992;79:1393–99.

    PubMed  CAS  Google Scholar 

  35. Carter RF, Abrams-Ogg ACG, Dick JE, et al. Autologous transplantation of canine long-term marrow culture cells genetically marked by retroviral vectors. Blood 1991; 79:356–64.

    Google Scholar 

  36. Moore KA, Deisseroth AB, Reading CL, Williams DE, Belmont JW. Stromal support enhances cell-free retroviral vector transduction of human bone marrow long-term culture-initiating cells. Blood 1992;79:1393–99.

    PubMed  CAS  Google Scholar 

  37. Molta JA, Hanley MB, Kohn DB. Sustained human hematopoiesis in immunodeficient mice by cotransplantation of marrow stroma expressing human IL-3: Analysis of gene transduction of long-lived progenitors. Blood 1994;83:3041–51.

    Google Scholar 

  38. Karlsson S, Bodine DM, Perry L, et al. Expression of the human β-globin gene following retroviral mediated transfer into multipotential hematopoietic progenitors of mice. Proc Natl Acad Sci USA 1988;85:6062–66.

    Article  PubMed  CAS  Google Scholar 

  39. Herrmann F, Brugger W, Kanz L, Mertelsmann. In vivo biology and therapeutic potential of hematopoietic growth factors and circulating progenitor cells. Seminars in Oncology 1992;19:422–31.

    PubMed  CAS  Google Scholar 

  40. Janssen WE. Peripheral blood and bone marrow hematopoietic stem cells: Are they the same. Seminars in Oncology 1993;20:19–27.

    PubMed  CAS  Google Scholar 

  41. Siena S, Bregni M, Brando B, Ravagnani F, Bonadonna G, Gianni AM. Circulation of CD34+ hematopoietic stem cells in the peripheral blood of high dose cyclophosphamide treated patients. Blood 1989;74:1905–14.

    PubMed  CAS  Google Scholar 

  42. Shimazaki C, Oku N, Ashihara E, et al. Collection of peripheral blood stem cells mobilized by high-dose Ara-C granulocyte-colony stimulating factor. Bone Marrow Transpl 1992;10:341–46.

    CAS  Google Scholar 

  43. Ahmed T, Wuest D, Ciavarella D. Peripheral blood stem cell mobilization by cytokines. J Clin Apheresis 1992;7:129–31.

    Article  PubMed  CAS  Google Scholar 

  44. Weaver CH, Buckner CD, Login K, et al. Syngeneic transplantation with peripheral blood mononuclear cells collected after administration of recombinant human granulocyte colony-stimulating factor. Blood 1993;82:1981–84.

    PubMed  CAS  Google Scholar 

  45. Cassel A, Cottier-Fox M, Doren S, Dunbar CE. Retroviral-mediated gene transfer into CD34-enriched human peripheral blood stem cells. Exp Hematol 1993;21:585–91.

    PubMed  CAS  Google Scholar 

  46. Bregni M, Magni M, Siena S, DiNicola M, Bonadonna G, Gianni AM. Human peripheral blood hematopoietic progenitors are optimal targets of retroviral-mediated gene transfer. Blood 1992;80:1418–22.

    PubMed  CAS  Google Scholar 

  47. Bodine DM, Seidel NE, Gale MS, Nienhuis AW, Orlic D. Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte-stimulating factor and stem cell factor. Blood 1993;82:445–55.

    PubMed  CAS  Google Scholar 

  48. Kerr WG, Mule JJ. Gene therapy: Current status and future prospects. J Leukocyte Biol 1994;56:210–24.

    PubMed  CAS  Google Scholar 

  49. Gluckman E, Broxmeyer HE, Auerbach A, et al. Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical cord blood from an HLA-identical sibling. N Engl J Med 1989;321:1174–78.

    Article  PubMed  CAS  Google Scholar 

  50. Karson EM, Polvino W, Anderson WF. Prospects for human gene therapy. J Reproductive Med 1992;37:508–14.

    CAS  Google Scholar 

  51. Diukman R, Golbus MS. In utero stem cell therapy. J Reproductive Med 1992;37: 515–20.

    CAS  Google Scholar 

  52. Moritz T, Keller DC, Williams DA. Human cord blood cells as targets for gene transfer: Potential use in genetic therapies of severe combined immunodeficiency disease. J Exp Med 1993;178:529–36.

    Article  PubMed  CAS  Google Scholar 

  53. Bodine DM, Seidel NE, Gale MS, Nienhuis AW, Orlic D. Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor. Blood 1994;84:1482–91.

    PubMed  CAS  Google Scholar 

  54. Sorrentino BP, Brandt SJ, Bodine D, et al. Selection of drug resistant bone marrow cells in vivo after retroviral transfer of human MDR-1. Science 1992;257:99–103.

    Article  PubMed  CAS  Google Scholar 

  55. Morgan RA, Cornetta K, Anderson WF. Applications of the polymerase chain reaction in retroviral-mediated gene transfer and the analysis of gene-marked human TIL cells. Hum Gene Ther 1990;1:135–49.

    Article  PubMed  CAS  Google Scholar 

  56. Topalian SL, Solomon D, Rosenberg SA. Tumor specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol 1989;142:3714–25.

    PubMed  CAS  Google Scholar 

  57. Rosenberg SA, Packard BS, Aebersold PM, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 1988;319:1676–80.

    Article  CAS  Google Scholar 

  58. Fisher B, Packard BS, Read EJ, et al. Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. J Clin Oncol 1989;7:250–61.

    PubMed  CAS  Google Scholar 

  59. The N2-TIL human gene transfer clinical protocol. Hum Gene Ther 1990;1:73-92.

    Google Scholar 

  60. Rosenberg SA, Lotze MT, Muul LM, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 1987;316:889–97.

    Article  PubMed  CAS  Google Scholar 

  61. Rill DR, Buschle M, Foreman NK, et al. Retrovirus-mediated gene transfer as an approach to analyze neuroblastoma relapse after autologous bone marrow transplantation. Hum Gene Ther 1992;3:129–36.

    Article  PubMed  CAS  Google Scholar 

  62. The University of Texas M.D. Anderson Cancer Center. Autologous bone marrow transplantation for CML in which retroviral markers are used to discriminate between relapse which arises from systemic disease remaining after preparative therapy versus relapse due to residual leukemia cells in autologous marrow: A pilot trial. Hum Gene Ther 1991;2:359–76.

    Article  Google Scholar 

  63. Brenner MK, Rill DR, Holladay MS, et al. Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patients. Lancet 1993;342: 1134–37.

    Article  PubMed  CAS  Google Scholar 

  64. Brenner MK, Rill DR, Moen RC, Krance RA, Mirro J, Anderson WF, Ihle JN. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet 1993;341:85–86.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Tulane University Medical School, USA

    S. M. Freeman & A. J. Marrogi

  2. Center for Biologics, Food and Drug Administration, USA

    K. A. Whartenby

  3. Department of Medicine, University of Rochester Medical Center, USA

    C. Abboud

Authors
  1. S. M. Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. J. Marrogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. A. Whartenby
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Abboud
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Red Cross Blood Bank Groningen-Drenthe, The Netherlands

    C. Th. Smit Sibinga  & P. C. Das  & 

  2. Leiden, The Netherlands

    E. Briët

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Freeman, S.M., Marrogi, A.J., Whartenby, K.A., Abboud, C. (1995). The Role of the Blood Bank in Human Gene Therapy Trials. In: Sibinga, C.T.S., Das, P.C., Briët, E. (eds) Hereditary Diseases and Blood Transfusion. Developments in Hematology and Immunology, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2017-7_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-2017-7_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5834-3

  • Online ISBN: 978-1-4615-2017-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation