Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letters to the Editor
  • Published:

Safety of retroviral gene marking with a truncated NGF receptor

Nature Medicine volume 9, pages 367–369 (2003)Cite this article

To the editor

Random integration into the host cell genome and inappropriate transgene expression are major safety concerns for the clinical use of retroviral vectors. Li et al. recently reported a leukemic transformation of mouse bone marrow cells caused by integration of a transgene-carrying retroviral vector into the Evi1 proto-oncogene. They suggested that expression of the transgene, a truncated form of the p75 low-affinity nerve growth factor receptor (ΔLNGFR) with most of the intracytoplasmic tail deleted (from residue 248), contributed to the leukemic progression1. Because ΔLNGFR is used as a surface marker in gene therapy clinical trials aimed at controlling graft-versus-host disease (GVHD) after bone marrow transplantation (BMT)2,3, a critical assessment of the potential risks associated with the use of such a molecule is essential.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Li, Z. et al. Murine leukemia induced by retroviral gene marking. Science 296, 497 (2002).

    Article  CAS  Google Scholar 

  2. Bordignon, C. & Bonini, C. A clinical protocol for gene transfer into peripheral blood lymphocytes for in vivo immunomodulation of donor anti-tumor immunity in patients affected by recurrent disease after allogeneic bone marrow transplantation. Hum. Gen. Ther. 2, 813–819 (1995).

    Article  Google Scholar 

  3. Bonini, C. et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276, 1719–1724 (1997).

    Article  CAS  Google Scholar 

  4. Rosenberg, N. & Jolicoeur, P. Retroviral pathogenesis. in Retroviruses (eds. Coffin, J.M., Hughes, S.H. & Varmus, H.) 413–416 (Cold Spring Harbor Laboratory Press, New York, 1997).

    Google Scholar 

  5. Hacein-Bey-Abina, S. et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N. Engl. J. Med. 348, 255–256 (2003).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Immunotherapy and Gene Therapy Program and Bone Marrow Transplantation Unit, Istituto Scientifico H.S. Raffaele and University Vita e Salute, Milan, Italy

    C. Bonini, F. Ciceri, S. Marktel, Z. Magnani, S. Cazzaniga, M. Bregni & C. Bordignon

  2. Georg-Speyer-Haus, Frankfurt, Germany

    M. Grez

  3. Molmed S.p.A., Milan, Italy

    C. Traversari, M. Radrizzani, C. Benati, S. Toma, C. Gallo-Stampino & C. Bordignon

  4. Department of Haematology, Faculty of Medicine, Imperial College Hammersmith Hospital, London, UK

    S. Marktel & J. Apperley

  5. H.S. Raffaele-Telethon Institute for Gene Therapy, Milan, Italy

    G. Ferrari, A. Aiuti, S. Deola & F. Lotti

  6. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA

    M. Dinauer & M. Sadat

  7. Department of Haematology, University Medical Center, Utrecht, The Netherlands

    A. Hagenbeek, S. Ebeling & A. Martens

  8. GSF-National Research Center for Environment and Health, Munich, Germany

    H.J. Kolb & M. Weber

  9. Department of Biomedical Sciences, University of Modena School of Medicine, Modena, Italy

    A. Grande & F. Mavilio

  10. Hematology and Oncology, Medical School, Hannover, Germany

    E. Weissinger

  11. Hematopoietic Gene Therapy Program, CIEMAT/Fundación Marcelino Botín, Madrid, Spain

    J.A. Bueren & M. Lamana

  12. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    J.H.F. Falkenburg & M.H.M. Heemskerk

  13. Liver Stem Cell Program, Stem Cells Inc., Palo Alto, California, USA

    T. Austin

  14. Department of Blood and Marrow Transplantation, Section of Molecular Hematology and Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    S. Kornblau & F. Marini

  15. Department of Immunology and Cell Biology, Molecular Immunohematology Laboratory, Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy

    M. Introna

  16. Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital, Jerusalem, Israel

    S. Slavin

  17. Fred Hutchinson Cancer Research Center and Department of Immunology and Medicine, Program of Immunology, University of Washington, Seattle, Washington, USA

    P.D. Greenberg

Authors
  1. C. Bonini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Grez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Traversari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Ciceri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Marktel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Ferrari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Dinauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Sadat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Aiuti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S. Deola
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M. Radrizzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A. Hagenbeek
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J. Apperley
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. S. Ebeling
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. A. Martens
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. H.J. Kolb
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. M. Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. F. Lotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. A. Grande
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. E. Weissinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. J.A. Bueren
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. M. Lamana
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. J.H.F. Falkenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. M.H.M. Heemskerk
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. T. Austin
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. S. Kornblau
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. F. Marini
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. C. Benati
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Z. Magnani
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. S. Cazzaniga
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. S. Toma
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. C. Gallo-Stampino
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. M. Introna
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. S. Slavin
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. P.D. Greenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  36. M. Bregni
    View author publications

    You can also search for this author in PubMed Google Scholar

  37. F. Mavilio
    View author publications

    You can also search for this author in PubMed Google Scholar

  38. C. Bordignon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Bonini.

Ethics declarations

Competing interests

C.T., M.R., C. Benati, S.T. and C.G.-S. are present full-time employees of Molmed S.p.A., an organization that could gain or lose financially through publication of this paper. T.A. is a former employee of SyStemix, a former subsidiary of Novartis that acquired intellectual property and rights on the work performed by SyStemix, and therefore could gain or lose financially by publication of this paper. M.I. is sponsored by Molmed S.p.A. F. Mavilio is a paid consultant of Molmed S.p.A. C. Bordignon is a member of the Board of Directors of Molmed S.p.A.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bonini, C., Grez, M., Traversari, C. et al. Safety of retroviral gene marking with a truncated NGF receptor. Nat Med 9, 367–369 (2003). https://doi.org/10.1038/nm0403-367

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0403-367

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing