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Enhancing immunity against melanoma using Type I interferon

Zemek, Rachael (2013) Enhancing immunity against melanoma using Type I interferon. Honours thesis, Murdoch University.

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Melanoma is an aggressive cancer, which when diagnosed in the late stages has a median survival rate of 6 months. The current gold-standard for adjuvant therapy is high doses of the type I interferon (IFN)-2, which prolongs disease free survival, but not overall survival. This high-dose therapy has many serious side-effects, resulting in doses to be lowered to sub-therapeutic levels. It is not clear how IFN-2 acts to treat melanoma, however it is accepted that immune enhancement is involved. The two main type I IFN families, IFN- and IFN-, signal via the same receptor, however they have been found to be functionally different. Of the IFN- family, 13 subtypes have been discovered and there is evidence that each is functionally unique. This project explores the therapeutic efficacy of seven type I IFN subtypes, including IFN-2 and IFN-, in treating melanoma. To test efficacy, a model of DNA therapy to administer plasmids encoding the IFN subtypes was combined with a melanoma model utilizing B16 F1 cells expressing the immunogenic peptide glycoprotein B. We have found that the IFN- subtypes tested have greater efficacy than IFN-2 in treating melanoma. The IFN subtypes delayed tumour onset, and one subtype demonstrated a significant increase in survival time. In addition, therapeutic effects could be seen when sera levels were lower than that of IFN-2. The in vitro effects of the IFN subtypes on melanoma cells was examined, uncovering differences in potency. Furthermore, we have found evidence of anti-tumour immune enhancement is associated with IFN- therapy but not IFN-. This research shows that the IFN- subtypes differ in their anti-tumour efficacy, and potency of actions. Therefore the IFN- subtypes show potential as a superior therapy in treating melanoma, which may be administered at lower, less toxic doses.

Publication Type: Thesis (Honours)
Murdoch Affiliation: School of Veterinary and Life Sciences
Supervisor: Waithman, J. and Fear, V.
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