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.

  • Article
  • Published:

DNA immunization induces protective immunity against B–cell lymphoma

Nature Medicine volume 2, pages 1038–1041 (1996)Cite this article

Abstract

Idiotypic determinants of the immunoglobuiin expressed on the surface of B–cell lymphomas are tumor–specific antigens (TSAs), which can be targeted by immunotherapy. Immunization with DNA constructs encoding the idiotype (Id) of a murine B–cell lymphoma induced specific anti–Id antibody responses and protected mice against tumor challenge. Use of DNA encoding an Id/GM–CSF (idiotype/granulocyte–macrophage colony–stimulating factor) fusion protein improved vaccine efficacy, and xenogeneic immunoglobuiin constant region determinants were required for immunogenicity. These results indicate that DNA may be a simple and efficacious means of inducing immune responses against a weak, otherwise unrecognized tumor antigen, provided that additional stimuli are included with the DNA.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Kaminski, M.S., Kitamura, K., Maloney, D.G. & Levy, R. Idiotype vaccination against murine B cell lymphoma: Inhibition of tumor immunity by free idiotype protein. J. Immunol. 38, 1289–1296 (1987).

    Google Scholar 

  2. George, A.J., Folkard, S.G., Hamblin, T.J. & Stevenson, F.K. Idiotypic vaccination as a treatment for a B cell lymphoma. J. Immunol. 141, 2168–2174 (1988).

    CAS  Google Scholar 

  3. Tao, M.H. & Levy, R. IdiotypeJgranulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma. Nature 362, 755–758 (1993).

    Article  CAS  Google Scholar 

  4. Kwak, L.W. et al. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N. Engl. J. Med. 327, 1209–1215 (1992).

    Article  CAS  Google Scholar 

  5. Hawkins, R.E. et al. Idiotypic vaccination against human B-cell lymphoma: Rescue of variable region gene sequences from biopsy material for assembly as single-chain Fv personal vaccines. Blood 83, 3279–3288 (1994).

    CAS  PubMed  Google Scholar 

  6. Watanabe, A. et al. Induction of antibodies to a kappa V region by gene immunization. J. Immunol. 151, 2871–2876 (1993).

    CAS  PubMed  Google Scholar 

  7. Hawkins, R.E., Winter, G., Hamblin, T.J., Stevenson, F.K. & SJ.A genetic approach to idiotypic vaccination. J. Immunother. 14, 273–278 (1993).

    Article  CAS  Google Scholar 

  8. Stevenson, F.K. et al. Idiotypic DNA vaccines against B-cell lymphoma. Immunol. Rev. 145, 211–228 (1995).

    Article  CAS  Google Scholar 

  9. Ulmer, J.B. et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259, 1745–1749 (1993).

    Article  CAS  Google Scholar 

  10. Xiang, Z.Q. et al. Vaccination with a plasmid vector carrying the rabies virus glycoprotein gene induces protective immunity against rabies virus. Virology 199, 132–140 (1994).

    Article  CAS  Google Scholar 

  11. Sedegah, M., Hedstrom, R., Hobart, P. & Hoffman, S.L. Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc. Natl. Acad. Sci. USA 91, 9866–9870 (1994).

    Article  CAS  Google Scholar 

  12. Irvine, K.R., Rao, J.B., Rosenberg, S.A. & Restifo, N.P. Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. J. Immunol. 156, 238–245 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Bergman, Y. & Haimovich, J. Characterization of a carcinogen-induced murine B lymphocyte cell line of C3HJeB origin. Eur. J. Immunol. 7, 413–317 (1977).

    Article  CAS  Google Scholar 

  14. Chen, T.T., Tao, M.H. & Levy, R. Idiotype-cytokine fusion proteins as cancer vaccines: Relative efficacy of IL-2, IL-4, and granulocyte-macrophage colony-stimulating factor. J. Immunol. 153, 4775–4787 (1994).

    CAS  Google Scholar 

  15. Slavin, S. & Strober, S. Spontaneous murine B-cell leukemia. Nature 272, 624–626 (1978).

    Article  CAS  Google Scholar 

  16. Germain, R.N. MHC-dependent antigen processing and peptide presentation: Providing ligands for T lymphocyte activation. Cell 76, 287–299 (1994).

    Article  CAS  Google Scholar 

  17. Xiang, Z. & Ertl, H.C. Manipulation of the immune response to a plasmid encoded viral antigen by coinoculation with plasmids expressing cytokines. Immunity 2, 129–135 (1995).

    Article  CAS  Google Scholar 

  18. Fynan, E.F. et al. DNA vaccines: Protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl. Acad. Set USA 90, 11478–11482 (1993).

    Article  CAS  Google Scholar 

  19. Raz, E. et al. Intradermal gene immunization: The possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Natl. Acad. Sci. USA 91, 9519–9523 (1994).

    Article  CAS  Google Scholar 

  20. Stevens, T.L. et al. Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature 334, 255–258 (1988).

    Article  CAS  Google Scholar 

  21. Reitan, S.K. & Hannestad, K. A syngeneic idiotype is immunogenic when borne by IgM but tolerogenic when joined to IgG. Eur. J. Immunol 25, 1601–1608 (1995).

    Article  CAS  Google Scholar 

  22. Chen, T.T. & Levy, R. Induction of autoantibody responses to GM-CSF by hyperimmunization with an Id-GM-CSF fusion protein. J. Immunol. 154, 3105–3117(1995).

  23. Reff, M.E. et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83, 435–445 (1994).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford University Medical Center, Room M207, Stanford, California, 94305-5306, USA

    Athanasia D. Syrengelas, Thomas T. Chen & Ronald Levy

Authors
  1. Athanasia D. Syrengelas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas T. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ronald Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Syrengelas, A., Chen, T. & Levy, R. DNA immunization induces protective immunity against B–cell lymphoma. Nat Med 2, 1038–1041 (1996). https://doi.org/10.1038/nm0996-1038

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0996-1038

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