Interleukins in Cancer Therapy: Rationale and Current Status

The interleukins function as intercellular hormones, and have the capacity to alter the activity of a target cell population. Immunotherapy with interleukin-2 (IL-2) constitutes a new treatment strategy for malignancies otherwise not responsive to traditional cytotoxic chemotherapy. In advanced renal cell carcinoma, studies using high dose bolus IL-2 alone have resulted in mean objective response rates of approximately 15% (0 to 27%). Durable responses in some patients have translated into increased survival. With advanced melanoma, high dose bolus IL-2 therapy alone produces response rates ranging from 21 to 24%, although other studies using lower doses, different drug preparations or different schedules have resulted in lower response rates. Studies are now under way using IL-2 in combination with interferons, cytotoxic chemotherapy, monoclonal antibodies and tumour infiltrating lymphocytes in an attempt to enhance the biological activity of IL-2. Another promising use of IL-2 therapy is in the treatment of acute leukaemia. Several small studies have shown benefit of IL-2 given to patients in early relapse, leading to normalisation of bone marrow and prolonged remissions in some patients. IL-2 is currently being investigated as a post-transplant adjuvant strategy in patients undergoing bone marrow transplantation for haematological malignancies. Newly characterised interleukins such as IL-4 and IL-6 have demonstrated preclinical antitumour and immunoenhancing properties, resulting in their recent introduction into clinical trials. Additionally, IL-6 has demonstrated thrombopoietic enhancing activity in early clinical trials and has a potential application in ameliorating thrombocytopenia associated with myeloablative chemotherapy. In summary, these interleukins have proven to be effective additions to treatment strategies in oncology.