EFFECTS OF LOW-DOSE RECOMBINANT INTERLEUKIN-2 IN HUMAN MALIGNANCIES

PURPOSE This article reviews the literature regarding the immunomodula tory activity and clinical efficacy of low-dose recombinant interleuki n-2 (rIL-2) therapy, The aim of future rIL-2 biotherapies for the trea tment of cancer is to standardize the lowest dosage of rIL-2 required to activate the in vivo anticancer immune response without harmful tox icity. PATIENTS AND METHODS Patients with various solid turner maligna ncies have been treated with either subcutaneous or intravenous low-do se rIL-2 at doses ranging from < 1 MIU/m(2)/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. RESULTS Prolonged and continuous injections of l ow-dose rIL-2 primarily increase activated T lymphocyte number, wherea s intermittent and sequential injections of low-dose rIL-2 seem to ind uce a preferential increase in activated natural killer cells and eosi nophils. Moreover, natural killer cells and eosinophil number increase progressively during the treatment, whereas T cells do not increase f urther after 2 weeks of treatment with low-dose rIL-2. The effect of l ow-dose rIL-2 is influenced by pretreatment systemic inflammation as w ell as neuroendocrine factors, such as pineal gland function, CONCLUSI ON Low-dose rIL-2 is not only less toxic than high-dose rIL-2 therapy, but is also the most physiologic immunotherapeutic strategy to activa te the anticancer immune response in vivo.