IL-2 in the therapy of melanoma and other malignancies

IL-2 as a single agent has been approved for use in both renal cancer and melanoma, and it has achieved widespread use in these malignancies for selected patients with metastatic disease. For these diseases, a role for IL-2-based therapy in the adjuvant setting has not been demonstrated, and current investigations involve the use of less toxic and less complex therapies. The activity of IL-2 has been studied extensively in other malignancies, particularly hematologic diseases such as leukemia and lymphoma. To date, IL-2 used either as a single agent or as a component of regimens containing one or more additional agents for diseases other than melanoma or renal cancer has shown promise, but the rapid emergence of safer agents for these and many other malignancies has tempered enthusiasm for IL-2-based regimens. Many investigations have been directed at enhancing the therapeutic ratio of IL-2, mostly by adding chemical modulators of downstream molecules associated with IL-2 toxicity. Other approaches, including variations on the chemical composition of IL-2 to alter its receptor-binding characteristics or its pharmacokinetic profile have been tried with limited success. The addition of targeting molecules co-administered with IL-2 or covalently bound to produce bispecific IL-2 containing molecules have shown promising activity and remain under investigation.