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Prime-boost vaccines encoding an intracellular idiotype/GM-CSF fusion protein induce protective cell-mediated immunity in murine pre-B cell leukemia

Gene Therapy volume 9, pages 503–510 (2002)Cite this article

Abstract

Two vaccines against an intracellularly expressed B cell idiotype were assessed for their ability to induce protective immunity in mice against challenge with a pre-B cell leukemia. One vaccine was based on a plasmid expression vector and the other was a recombinant vaccinia virus; both vaccines expressed a polypeptide derived from the complementarity-determining regions (CDR2-CDR3) of the leukemic clone-specific immunoglobulin heavy chain (IgH), as a fusion product with mouse granulocyte–macrophage colony-stimulating factor (mGM-CSF). Mice inoculated with either vaccine showed significantly higher survival rates than controls after challenge with leukemia cells. However, protection from tumor challenge was optimal when the DNA vaccine was used for priming, followed by a booster immunization with the vaccinia virus recombinant. This vaccination protocol induced resistance not only to the first tumor challenge given shortly afterwards, but also to a second challenge given months later. Both CD4+ and CD8+ T cells contributed to protection in vaccinated mice. These data suggest that such a vaccine regimen might reduce the incidence of recurrence in patients with minimal residual disease after conventional therapy.

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Acknowledgements

We thank Dr A Cesano for helpful discussion, Dr Andy Caton and Dr Helen Hurst for reviewing the manuscript, S Shane for technical assistance. This work was supported by the Imperial Cancer Research Fund, Help Hammer Cancer and grants from NCI and NIAID.

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Authors and Affiliations

  1. ICRF Molecular Oncology Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK

    S Pasquini, E Missiaglia, L Carta & N R Lemoine

  2. The Wistar Institute, Philadelphia, PA, USA

    S Pasquini & S Peralta

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  1. S Pasquini
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Pasquini, S., Peralta, S., Missiaglia, E. et al. Prime-boost vaccines encoding an intracellular idiotype/GM-CSF fusion protein induce protective cell-mediated immunity in murine pre-B cell leukemia. Gene Ther 9, 503–510 (2002). https://doi.org/10.1038/sj.gt.3301677

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