Lessons from the clinical trials of interleukin-2.
The initial results of interleukin-2 (IL-2) therapy in man are reviewed from the perspective of how they conform to predictions from preclinical studies. These preclinical models predict that tumors will vary in their susceptibility to IL-2 therapy and will be most successfully treated at lower tumor burdens. In addition, the dose and schedule of IL-2 are important for successful therapy. Host-related factors, including the presence of suppressor activities, may also be important. In these models, the addition of other cytokines, including interferon-alpha or tumor necrosis factor, to IL-2 can enhance antitumor activity. The concomitant administration of ex vivo IL-2-activated lymphokine-activated killer cells or tumor-infiltrating lymphocytes also enhances the IL-2 antitumor effect. Clinical trials addressing all of these issues have been completed or are underway; the results suggest overall that the preclinical models are predictive, with both host- and tumor-related factors as well as such IL-2-therapy-related factors as dose, schedule, route and the use of additional agents all playing a role in the success of therapy. A more complete understanding of the mechanisms of response and resistance involved in this therapy will facilitate the rational development of more effective and less toxic IL-2-based therapy of human malignancy.
Parkinson
D R
DR
Department of Clinical Immunology and Biological Therapy, University of Texas, M.D. Anderson Cancer Center, Houston.
D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D010358:Patient Participation
D016207:Cytokines; D004338:Drug Combinations; D007376:Interleukin-2