A Kunjin replicon vector encoding granulocyte macrophage colony-stimulating factor for intra-tumoral gene therapy.
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.
Hoang-Le
D
D
Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland, Australia.
Smeenk
L
L
Anraku
I
I
Pijlman
G P
GP
Wang
X J
XJ
de Vrij
J
J
Liu
W J
WJ
Le
T T
TT
Schroder
W A
WA
Khromykh
A A
AA
Suhrbier
A
A
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D005416:Flavivirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D012093:Replicon / Q000235:genetics*
D019496:Cancer Vaccines; D016898:Interferon-alpha; D016899:Interferon-beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor