Immunotherapies for Targeting Ancient Retrovirus during Breast Cancer.

摘要

During the human genome project, a set of ancient retrovirus named Human endogenous retrovirus (HERVs) was discovered to be stably integrated into the human genome forming 8.5% of the total human genome1. Among the HERVs, HERV- K was found as an oncogenic allelic variant involved in melanoma, breast cancer, ovarian cancer, tretatocarcinoma and prostate cancer along with various autoimmune diseases like multiple sclerosis and rheumatoid arthritis. The oncogenic potential of HERV-K is contributed by the envelope (env) and GAG protein (Rec). Recent studies have shown that the expression of the HERV-K env protein exclusively on tumor cell surface and not on normal skin cells. The expression of HERVK env protein was found to increase with more aggressive and metastatic type III and type IV melanoma than less aggressive and localized type I melanoma. This selective expression of HERV-K env protein on melanoma cells can be harnessed as a treatment strategy for patients with refractory or metastatic melanoma. Patients with metastatic melanoma have a poor prognosis due to resistance to conventional therapies such as chemotherapy, radiation and surgery. Thus, new targeted treatment strategies are required to improve therapeutic outcome.