A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy

D. Hoang-Le, L. Smeenk, I. Anraku, G.P. Pijlman, X.J. Wang, J. de Vrij, W.J. Liu, T.T. Le, W.A. Schroder, A.A. Khromykh, A. Suhrbier

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15 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)190-199
JournalGene Therapy
Volume16
DOIs
Publication statusPublished - 2009

Keywords

  • west-nile-virus
  • cd8 t-cells
  • human dendritic cells
  • amino-acid substitution
  • cytokine gene-therapy
  • gm-csf
  • ifn-alpha
  • in-vivo
  • cancer-immunotherapy
  • clonal expansion

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