Cancer therapy using a self-replicating RNA vaccine View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-07

AUTHORS

Han Ying, Tal Z. Zaks, Rong-Fu Wang, Kari R. Irvine, Udai S. Kammula, Francesco M. Marincola, Wolfgang W. Leitner, Nicholas P. Restifo

ABSTRACT

'Naked' nucleic acid vaccines are potentially useful candidates for the treatment of patients with cancer, but their clinical efficacy has yet to be demonstrated. We sought to enhance the immunogenicity of a nucleic acid vaccine by making it 'self-replicating'. We accomplished this by using a gene encoding an RNA replicase polyprotein derived from the Semliki forest virus, in combination with a model antigen. A single intramuscular injection of a self-replicating RNA immunogen elicited antigen-specific antibody and CD8+ T-cell responses at doses as low as 0.1 microg. Pre-immunization with a self-replicating RNA vector protected mice from tumor challenge, and therapeutic immunization prolonged the survival of mice with established tumors. The self-replicating RNA vectors did not mediate the production of substantially more model antigen than a conventional DNA vaccine did in vitro. However, the enhanced efficacy in vivo correlated with a caspase-dependent apoptotic death in transfected cells. This death facilitated the uptake of apoptotic cells by dendritic cells, providing a potential mechanism for enhanced immunogenicity. Naked, non-infectious, self-replicating RNA may be an excellent candidate for the development of new cancer vaccines. More... »

PAGES

823

Journal

TITLE

Nature Medicine

ISSUE

7

VOLUME

5

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/10548

    DOI

    http://dx.doi.org/10.1038/10548

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039878034

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10395329


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    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/10548'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/10548'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/10548'

    RDF/XML is a standard XML format for linked data.

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