Melanoma is an aggressive and malignant cancer of melanocytes. The incidence of melanoma is increasing worldwide. Australia is known to have the highest incidence of melanoma in the world and when diagnosed in its advanced metastatic stages, patients have a median survival time of six months. Currently high doses of type I interferon (IFN)-α2 are a gold standard therapy for treating high-risk melanoma patients. However, recent data show that greater relapse-free survival for one year in phase III trials but does not improve overall survival. In addition, adverse effects have also been reported with this high dose interferon therapy bringing into question the continued use of this treatment.
From the 14 IFN-α subtypes, only IFN-α2 has been investigated as a treatment for melanoma, leaving the remaining 13 subtypes unexplored as potential options.
We have cloned six IFN-α subtypes into retroviral vectors and transduced the murine melanoma cell line B16. These genetically modified B16-IFN-α melanoma cells will be grafted into syngeneic mice to determine if IFN-α subtype expression alters the growth kinetics of the B16-IFN-α melanoma cells compared to control B16 melanoma cells.
If a B16-IFN-α subtype is identified that alters growth kinetics, the cells will be transplanted into mice lacking the type I IFN receptor. In this setting, the immune cells cannot respond to type I IFN, and if no difference in tumour growth is observed the results will support that enhanced tumour control is immune mediated.
The outcomes from this project may enable better treatment options for patients with melanoma.