Interleukin-2 and Cancer Therapy

Abstract

IL-2 was originally isolated as a soluble factor with the property of enhancing T-lymphocyte proliferation in studies of the human immunodeficiency virus (1). The earliest studies of its activity in the cellular therapy of cancer used partially-purified IL-2 from the Jurkat human T-cell line. Subsequent studies used recombinant IL-2 produced in E. coli, an unlimited source of this valuable cytokine that has been used more than any other immunologic agent for laboratory and clinical investigations of immunotherapy for malignant and nonmalignant disease. Proof of concept for the potent activity of IL-2-activated killer cells (termed lymphokine-activated killer, or LAK cells) against established malignancy in animal models was provided in the extensive series of reports from Rosenberg and the Surgery Branch of the National Cancer Institute beginning in the mid-1980s (2–4). The earliest human studies used Jurkat-derived IL-2 and ex vivo-activated autologous LAK cells derived from leukapheresis of patients with advanced cancer. These patients initially received intravenous IL-2 before mononuclear cell collections and then received additional IL-2 following the re-infusion of autologous lymphocytes that had undergone further exposure to IL-2 ex vivo for several days. The encouraging level of activity against renal cancer and melanoma, including a 5–7% rate of durable complete remission, was particularly gratifying in light of the marked resistance of these two malignancies to chemotherapy and other biologic agents such as interferon. Subsequent clinical trials demonstrated that ex vivo exposure of patient cells to IL-2 was not necessary, as the in vivo exposure appeared to be associated with a comparable likelihood of antitumor response (5).At the same time, the success of this approach at centers outside of the National Cancer Institute was confirmed with a series of studies by the Cytokine Working Group and other institutions (6–9).