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Abstract
The development of recombinant interleukin-2 (rIL-2) as a treatment for cancer represented an important milestone in the development of biologic therapies. IL-2 is a natural modulator of the immune system that stimulates specialised immune system cells, namely cytotoxic T-lymphocytes (CTLs) and natural killer cells (NKCs). These cells could potentially recognise and destroy tumour cells throughout the body. However, the exact mechanism(s) by which IL-2 mediates a tumouricidal effect is not well known. Recombinant IL-2 has been primarily used in the treatment of advanced renal cell cancer (RCC) and malignant melanoma (MM). Nevertheless, the benefit of rIL-2 therapy remains very modest in these conditions. Initial results demonstrated objective response rates (shrinkage of tumour volume to less than 50%) in the 15 - 20% range with some durable responses. However, the overall response rates were lower than originally hoped for with this therapy. Moreover, the use of rIL-2 may be associated with significant side effects that could be life threatening. Despite numerous studies with rIL-2, the optimal dose and treatment schedules remain a controversial topic. To date, there are no clear immunological parameters able to predict biological response to rIL-2 administration to achieve maximum therapeutic index. In addition, combination therapy with either immunomodulators or cytotoxic drugs, is being very actively investigated.