The role of IL-2 in gene therapy

Interleukin-2 (IL-2) is a growth factor for T-cells which enhances both non-specific immune responses such as natural killer (NK) and lymphokine-activated killer (LAK) cells as well as MHC-restricted cytotoxic T-cell responses. Early studies using IL-2 to treat a number of advanced cancers suggested that it may be active against malignant melanoma and renal cell carcinoma. However, responses were at the expense of considerable morbidity and mortality. Those, and subsequent studies, which aimed at increasing the efficacy and reducing the toxicity of IL-2-based treatments, are briefly reviewed and the current situation in which IL-2 is being used more frequently, in low dose subcutaneously administered regimens (often in combination with other agents such as alpha-interferon) assessed. The ultimate application of IL-2 against human cancer may be when it is secreted either by tumour-infiltrating lymphocytes or the tumour cells themselves. A number of studies using this approach are about to commence or have already started. Tumour cells transduced with IL-2 could effectively act as a therapeutic vaccine against low volume disease.