Effects of low-dose recombinant interleukin-2 in human malignancies

This article reviews the literature regarding the immunomodulatory activity and clinical efficacy of low-dose recombinant interleukin-2 (rIL-2) therapy. The aim of future rIL-2 biotherapies for the treatment of cancer is to standardize the lowest dosage of rIL-2 required to activate the in vivo anticancer immune response without harmful toxicity.

Patients with various solid tumor malignancies have been treated with either subcutaneous or intravenous low-dose rIL-2 at doses ranging from < 1 MIU/m2/day to 6 MIU/day. In these studies the immunomodulatory effects of low-dose rIL-2 administration have been evaluated by measuring cytokine production and immune cell numbers and activity.

Prolonged and continuous injections of low-dose rIL-2 primarily increase activated T lymphocyte number, whereas intermittent and sequential injections of low-dose rIL-2 seem to induce a preferential increase in activated natural killer cells and eosinophils. Moreover, natural killer cells and eosinophil number increase progressively during the treatment, whereas T cells do not increase further after 2 weeks of treatment with low-dose rIL-2. The effect of low-dose rIL-2 is influenced by pretreatment systemic inflammation as well as neuroendocrine factors, such as pineal gland function.

Low-dose rIL-2 is not only less toxic than high-dose rIL-2 therapy, but is also the most physiologic immunotherapeutic strategy to activate the anticancer immune response in vivo.