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Gene Ther ; 16(2): 190-9, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19092857

ABSTRACT

We have recently developed a non-cytopathic RNA replicon-based viral vector system based on the flavivirus Kunjin. Here, we illustrate the utility of the Kunjin replicon system for gene therapy. Intra-tumoral injections of Kunjin replicon virus-like particles encoding granulocyte colony-stimulating factor were able to cure >50% of established subcutaneous CT26 colon carcinoma and B16-OVA melanomas. Regression of CT26 tumours correlated with the induction of anti-cancer CD8 T cells, and treatment of subcutaneous CT26 tumours also resulted in the regression of CT26 lung metastases. Only a few immune-based strategies are able to cure these aggressive tumours once they are of a reasonable size, illustrating the potential of this vector system for intra-tumoral gene therapy applications.


Subject(s)
Colonic Neoplasms/therapy , Genetic Therapy/methods , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Melanoma, Experimental/therapy , Replicon/genetics , Animals , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/therapeutic use , Colonic Neoplasms/immunology , Flavivirus/genetics , Genetic Vectors , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , Interferon-alpha/biosynthesis , Interferon-beta/biosynthesis , Lung Neoplasms/prevention & control , Lung Neoplasms/secondary , Melanoma, Experimental/immunology , Mice , Neoplasm Transplantation
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