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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.

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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.

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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.

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  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

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  1. Catherine A. King
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Correspondence to Freda K. Stevenson.

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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

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