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 vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma

Nature Medicine volume 4, pages 1281–1286 (1998)Cite this article

Abstract

Vaccination with idiotypic protein protects against B-cell lymphoma, mainly through anti-idiotypic antibody. For use in patients, DNA vaccines containing single-chain Fv derived from tumor provide a convenient alternative vaccine delivery system. However, single-chain Fv sequence alone induces low anti-idiotypic response and poor protection against lymphoma. Fusion of the gene encoding fragment C of tetanus toxin to single-chain Fv substantially promotes the anti-idiotypic response and induces strong protection against B-cell lymphoma. The same fusion design also induces protective immunity against a surface Ig-negative myeloma. These findings indicate that fusion to a pathogen sequence allows a tumor antigen to engage diverse immune mechanisms that suppress growth. This fusion design has the added advantage of overcoming potential tolerance to tumor that may exist in patients.

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

Figure 1: Antibody responses against FrC or A31IgM induced by DNA vaccines.
Figure 2: Reactivity of antibodies induced by DNA fusion vaccines with target tumor cells as assessed by immunofluorescence.
Figure 3: Antibody responses against FrC or against 5T33Fab induced by DNA vaccines.
Figure 4: Antibody responses against 5T33Fab induced by DNA vaccines requires gene fusion.
Figure 5: Induction of CTLs against FrC by the DNA fusion vaccine.
Figure 6: Induction of protective immunity against the A31 lymphoma by the DNA fusion vaccine.
Figure 7: Induction of protective immunity against the 5T33 myeloma by the DNA fusion vaccine.
Figure 8: Effect of pre-vaccination with tetanus toxoid on induction of anti-Id antibodies by the p.scFv5T33–FrC construct.

Similar content being viewed by others

References

  1. Eisen, H.N., Sakato, N. & Hall, S.J. Myeloma proteins as tumor-specific antigens. Transplant. Proc. 7, 209–214(1975).

    CAS  PubMed  Google Scholar 

  2. George, A.J.T. & Stevenson, F.K. Prospect for the treatment of B cell tumors using idiotypic vaccination. Int. Rev. Immunol. 4,271–310(1989).

    Article  CAS  Google Scholar 

  3. Kaminski, M.S., Kitamura, K., Maloney, D.G. & Levy, R. Idiotypic vaccination against a murine B cell lymphoma: inhibition of tumor immunity by free idiotypic protein. J. Immunol. 138, 1289–1296(1987).

    CAS  PubMed  Google Scholar 

  4. Hsu, F.J. et al. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma-long term results of a clinical trial. Blood 89, 3129–3135( 1997).

    CAS  PubMed  Google Scholar 

  5. Hsu, F.J. et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med. 2, 52–58 (1996).

    Article  CAS  Google Scholar 

  6. Davis, H.L. & Whalen, R.G. in Molecular and Cell Biology of Human Gene Therapeutics (ed. Dickson, G.) 368 (Chapman & Hall, London, 1995).

    Book  Google Scholar 

  7. Conry, R.M., LoBuglio, A.F. & Curiel, D.T. Polynucleotide-mediated immunization therapy of cancer. Semin. Oncol. 23, 135– 147(1996).

    CAS  PubMed  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. Syrenglas, A.D., Chen, T.T. & Levy, R. DNA immunization induces protective immunity against B cell lymphoma. Nature Med. 2, 1038– 1041(1996).

    Article  Google Scholar 

  10. Kumar, A., Arora R., Kaur, P., Chauhan, V.S. & Sharma, P. "Universal" T helper cell determinants enhance immunogenicity of a Plasmodium falciparum merozoite surface antigen peptide. J. Immunol. 148, 1499–1505(1992).

    CAS  PubMed  Google Scholar 

  11. Spellerberg, M.B. et al. Promotion of anti-idiotypic antibody responses induced by single chain Fv genes by fusion to Tetanus Toxin Fragment C. J. Immunol. 159, 1885–1892( 1997).

    CAS  PubMed  Google Scholar 

  12. Anderson, R. & Gao, X.-M., Papakonstantinopolou, A., Roberts, M. & Dougan, G. Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin. Infect. Immun. 64, 3168–3173( 1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Manning, L.S. et al. A model of multiple myeloma: Culture of 5T33 murine myeloma cells and evaluation of tumorgenicity in the C57BL/KaLRij mouse. Br. J. Cancer 66, 1088–1093(1992).

    Article  CAS  Google Scholar 

  14. Rammensee, H.-G., Rötzschke, O. & Falk, K. MHC Class I-restricted antigen processing-lessons from natural ligands. Chem. Immunol. 57, 113– 133(1993).

    CAS  PubMed  Google Scholar 

  15. Bogen, B. Peripheral T cell tolerance as a tumor escape mechanism: deletion of CD4+ T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma. Eur. J. Imunol. 26, 2671 –2679(1996).

    Article  CAS  Google Scholar 

  16. Dyke, R.J. et al. Idiotypic vaccination against B-cell lymphoma leads to dormant tumor. Cell. Immunol. 132, 70– 83(1991).

    Article  CAS  Google Scholar 

  17. Scheuermann, R.H. & Uhr, J.W. Connections between signal transduction components and cellular responses initiated by antigen receptor on B lymphocytes. J. Exp. Med. 182, 903–906(1995).

    Article  CAS  Google Scholar 

  18. Wilson, A., George, A.J.T., King, C.A. & Stevenson, F.K. Recognition of a B cell lymphoma by anti-idiotypic T cells. J. Immunol. 145, 3973–3943( 1990).

    Google Scholar 

  19. Hawkins, R.E., Russell, S.J., Hamblin, T. & Stevenson, F. Clinical protocol. A pilot study of idiotypic vacination for follicular B-cell lymphoma using a genetic approach. Hum. Gene Ther. 8, 1287–1299(1997).

    Article  CAS  Google Scholar 

  20. Vollmers, H. P. et al. A rapid method for purification of monoclonal human IgM from mass culture. Hum. Antibod. Hybridomas 7, 37–41(1996).

    Article  CAS  Google Scholar 

  21. Zhu, D. et al. Immunoglobulin VH gene sequence analysis of spontaneous immunoglobulin-secreting B-cell tumors with clinical features of human disease. Immunology 93, 162–170 (1998).

    Article  CAS  Google Scholar 

  22. Huse, W.D. et al. Generation of a large combinational library of the immunoglobulin repertoire in phage lambda. Science 246, 1275–1281(1989).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Leukaemia Research Fund, Tenovus, and the Cancer Research Campaign, UK. We also thank the Kathy Giusti Multiple Myeloma Research Foundation for support.

Author information

Authors and Affiliations

  1. Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Southampton, SO16 6YD, England

    Catherine A. King, Myfanwy B. Spellerberg, Delin Zhu, Jason Rice, Surinder S. Sahota, Andrew R. Thompsett, Terry J. Hamblin, Jiri Radl & Freda K. Stevenson

Authors
  1. Catherine A. King
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myfanwy B. Spellerberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Delin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jason Rice
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Surinder S. Sahota
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew R. Thompsett
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Terry J. Hamblin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jiri Radl
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Freda K. Stevenson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Freda K. Stevenson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

King, C., Spellerberg, M., Zhu, D. et al. DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma. Nat Med 4, 1281–1286 (1998). https://doi.org/10.1038/3266

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/3266

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