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Cytokine Engineering for Cancer Immunotherapy

Interleukin-2 (IL-2) is a cytokine that has been extensively studied for use against cancer, and is currently approved for the treatment of renal cell carcinoma and melanoma. IL-2 creates an immune response against cancer by stimulating the proliferation of activated cytotoxic T lymphocytes and natural killer cells. However, the response rate of IL-2 therapy for cancer remains low. One possible explanation for this is that IL-2 also activates CD4+ CD25+ regulatory T (Treg) cells, which have an immunosuppressive activity that counteracts the anti-cancer effect of IL-2. In this project, I aim to engineer IL-2 for optimized activity in the context of activating an anti-cancer response and preventing suppression by Treg cells. By engineering the interactions of IL-2 with its heterotrimeric receptor, the effects of IL-2 on the immune system can be modulated for improved therapeutic efficacy.