In 1999 Ontak was approved by the U.S. Food and Drug Administration (FDA) for treatment of cutaneous T cell lymphoma (CTCL). Preclinical research
IL-2 does not follow the classical dose-response curve of chemotherapeutics. The immunological activity of high and low dose IL-2 show sharp contrast. This might be related to different distribution of IL-2 receptors (CD25, CD122, CD132) on different cell populations, resulting in different cells that are activated by high and low dose IL-2. In general high doses are immune suppressive, while low doses can stimulate type 1 immunity. Low-dose IL-2 has been reported to reduce hepatitis C and B infection.IL-2 has been used in clinical trials for the treatment of chronic viral infections and as a booster (adjuvant) for vaccines. The use of large doses of IL-2 given every 6–8 weeks in HIV therapy, similar to its use in cancer therapy, was found to be ineffective in preventing progression to an AIDS diagnosis in two large clinical trials published in 2009.More recently low dose IL-2 has shown early success in modulating the immune system in disease like type 1 diabetes and vasculitis. There are also promising studies looking to use low dose IL-2 in ischaemic heart disease. IL-2/anti-IL-2 mAb immune complexes (IL-2 ic)
IL-2 cannot accomplish its role as a promising immunotherapeutic agent due to significant drawbacks which are listed above. Some of the issues can be overcome using IL-2 ic. They are composed of IL-2 and some of its monoclonal antibody (mAb) and can potentiate biologic activity of IL-2 in vivo.
: 76 Commercial activity to bring an IL-2 drug to market was intense in the 1980s and 90s. By 1983, Cetus Corporation had created a proprietary recombinant version of IL-2 (Aldesleukin, later branded as Proleukin), with the alanine removed from its N-terminal and residue 125 replaced with serine. : 76–77 : 201  Amgen later entered the field with its own proprietary, mutated, recombinant protein and Cetus and Amgen were soon competing scientifically and in the courts; Cetus won the legal battles and forced Amgen out of the field. : 151   By 1990 Cetus had gotten aldesleukin approved in nine European countries but in that year, the U.S. Food and Drug Administration (FDA) refused to approve Cetus application to market IL-2. The failure led to the collapse of Cetus, and in 1991 the company was sold to Chiron Corporation. Chiron continued the development of IL-2, which was finally approved by the FDA as Proleukin for metastatic renal carcinoma in 1992.By 1993 aldesleukin was the only approved version of IL-2, but Roche was also developing a proprietary, modified, recombinant IL-2 called teceleukin, with a methionine added at is N-terminal, and Glaxo was developing a version called bioleukin, with a methionine added at is N-terminal and residue 125 replaced with alanine. Dozens of clinical trials had been conducted of recombinant or purified IL-2, alone, in combination with other drugs, or using cell therapies, in which cells were taken from patients, activated with IL-2, then reinfused.