Interleukin-2, recombinant preparation

Aldesleukin is with recombinant technology prepared interleukin-2 (IL-2). IL-2 binds to the IL-2 receptor and so stimulates proliferation of T-helper cells and cytotoxic T-cells. It also activates macrophages and stimulates B-cell activity. It is used in metastasized renal carcinoma. Life threatening car-diotoxicity may occur. Other adverse effects include bone marrow depression and neurotoxicity with manifestations varying from somnolence to delirium. 

Walsh (2003) defined biopharmaceuticals as therapeutic protein or nucleic acid preparations made by techniques involving recombinant deoxyribonucleic acid (DNA) technology. Therapeutic proteins include blood clotting factors and plasminogen activators, hemopoietic factors, hormones, interferons and interleukins, and monoclonal antibodies (LeVine, 2006). Over time, the term biopharmaceutical has broadened, and, in addition to proteins and nucleic acids, now includes bacteriophages, viral and bacterial vaccines, vectors for gene therapy, and cells for cell therapy (Primrose and Twyman, 2004). Attention here focuses on proteins, since the majority of approved biopharmaceuticals are proteins. 

Recombinant human interleukin-4 (rhIL-4) is a monomeric protein with a molecular weight of 15,400 Da and pi of 9.2, with three intrachain disulfide bonds. It is a cytokine that has been investigated for cancer therapy. CZE of rhIL-4 mixtures prepared by in vitro degradation has been performed in uncoated capillaries with 50 m M 1,3-diaminopropane and phosphate buffers with pH ranging from 4.5 to 8.O.40 The resolution of degradation products by CZE appeared to be superior to HPLC. 

Interleukin-2 Human recombinant lL-2 aldesleukin, proleukin des-alanyl-1, serine-125 human lL-2) differs from native lL-2 in that it is not glycosylated, has no amino terminal Ala, and has an Ser substituted for the Cys at amino acid 125. The potency of the preparation is represented in International Units in a lymphocyte proliferation assay such that 1.1 mg of recombinant lL-2 protein equals 18 million International Units. Aldesleukin has the following in vitro biologic activities of native lL-2 enhancement of lymphocyte proliferation and growth of lL-2-dependent cell lines enhancement of lymphocyte-mediated cytotoxicity and killer cell activity and induction of interferon-7 activity. In vivo administration of aldesleukin in animals produces multiple immunologic effects in a dose-dependent manner. Cellular immunity is profoundly activated with lymphocytosis, eosinophilia, thrombocytopenia, and release of multiple cytokines e.g., TNF-a, lL-1, interferon-7). Aldesleukin is indicated for the treatment of adults with metastatic renal cell carcinoma and melanoma. Administration of aldesleukin has been associated with serious cardiovascular toxicity resulting from capillary leak syndrome, which involves loss of vascular tone and leak of plasma proteins and fluid into the extravascular space. Hypotension, reduced organ perfusion, and death may occur. An increased risk of disseminated infection due to impaired neutrophil function also has been associated with aldesleukin treatment. 

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