title: Interleukin-2 in the treatment of renal cancer.
abstract: Interleukin-2 (IL-2) administered in pharmacologic doses to renal cancer patients with intact organ function and good performance status induces durable complete responses in about 5% of patients and partial responses in an additional 10% to 15%. The mechanism of antitumor efficacy of IL-2 is closely related to its ability to expand and activate cytotoxic lymphocytes of the natural killer (NK)- and thymic (T)-cell subsets that express IL-2 receptors (IL-2R). There is also accumulating evidence that local or generalized effector cell dysfunction, which is characteristic of patients with advanced cancer, can be reversed with IL-2 exposure. The toxicities of IL-2 are mediated by cytokines and other small molecules secreted by IL-2R-expressing cells responding to the binding of this ligand. The common mechanism for IL-2-induced multiorgan dysfunction appears to be a capillary leak syndrome directly mediated by local production of nitric oxide by cells of the monocyte-macrophage lineage. To date, efforts to improve on the antitumor activity of IL-2 by the addition of IL-2-activated peripheral blood mononuclear cells (lymphokine-activated killer [LAK] cells) or cell subsets selected for proximity or potential antigen-specificity (tumor-infiltrating lymphocytes [TIL]) have not led to improved therapeutic outcomes. Attempts to reduce the risks of IL-2 therapy (which could potentially allow for increased IL-2 administration) by blocking one or more of the known mediators of toxicity have also been disappointing. Current research is directed at developing combination regimens with additive or synergistic antitumor effects and incompletely overlapping toxicities, as well as the identification of tumor antigens that may be the target of more focused cellular therapies. The role of high-dose IL-2 in the adjuvant therapy of resected renal cancer at high risk of relapse is also under investigation.
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Cancer, Duarte, CA 91010, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Margolin
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D017321:Clinical Trials, Phase I as Topic; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000637:transplantation; D009392:Nephrectomy; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2