mRNA-based cancer vaccine: prevention of B16 melanoma progression and metastasis by systemic injection of MART1 mRNA histidylated lipopolyplexes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-09

AUTHORS

M Mockey, E Bourseau, V Chandrashekhar, A Chaudhuri, S Lafosse, E Le Cam, V F J Quesniaux, B Ryffel, C Pichon, P Midoux

ABSTRACT

Immunization with mRNA encoding tumor antigen is an emerging vaccine strategy for cancer. In this paper, we demonstrate that mice receiving systemic injections of MART1 mRNA histidylated lipopolyplexes were specifically and significantly protected against B16F10 melanoma tumor progression. The originality of this work concerns the use of a new tumor antigen mRNA formulation as vaccine, which allows an efficient protection against the growth of a highly aggressive tumor model after its delivery by intravenous route. Synthetic melanoma-associated antigen MART1 mRNA was formulated with a polyethylene glycol (PEG)ylated derivative of histidylated polylysine and L-histidine-(N,N-di-n-hexadecylamine)ethylamide liposomes (termed histidylated lipopolyplexes). Lipopolyplexes comprised mRNA/polymer complexes encapsulated by liposomes. The tumor protective effect was induced with MART1 mRNA carrying a poly(A) tail length of 100 adenosines at an optimal dose of 12.5 microg per mouse. MART1 mRNA lipopolyplexes elicited a cellular immune response characterized by the production of interferon-gamma and the induction of cytotoxic T lymphocytes. Finally, the anti-B16 response was enhanced using a formulation containing both MART1 mRNA and MART1-LAMP1 mRNA encoding the antigen targeted to the major histocompatibility complex class II compartments by the lysosomal sorting signal of LAMP1 protein. Our results provide a basis for the development of mRNA histidylated lipopolyplexes for cancer vaccine. More... »

PAGES

802

References to SciGraph publications

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  • Journal

    TITLE

    Cancer Gene Therapy

    ISSUE

    9

    VOLUME

    14

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.cgt.7701072

    DOI

    http://dx.doi.org/10.1038/sj.cgt.7701072

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1005129746

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17589432


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