Clinical advances in therapies targeting the interleukin-2 receptor

A dominant theme in modern immunological research is the elucidation of how the different branches of the immune system communicate. Identification of receptors for antigens, co‐receptors such as CD4 and CD8, major histocompatibility complex (MHC) molecules and cytokine receptors, has gone a long way to giving a clearer view of the complexities of this interaction. More recently, this new information has opened up avenues for therapeutic intervention by directing novel treatments towards these various receptors. This new strategy of immune‐receptor‐directed therapy has been applied to an array of human disorders both in the laboratory and clinical settings. Perhaps one of the most important, and certainly most studied, cytokines is interleukin‐2 (IL‐2). This molecule was first identified in 1976 by Morgan as a substance present in the supernatant of activated peripheral blood lymphocytes that was capable of driving the growth and proliferation of lymphocytes in vivo .1 Recent molecular biological advances have allowed development of recombinant IL‐2 and inhibitors of its cellular receptor. This review focuses on the basic biology of IL‐2 and its receptor, and examines the clinical applications of IL‐2 receptor‐targeted therapies. Recombinant IL‐2 has also been extensively used in treatment of various malignancies, but for reasons of space, I will not further examine this issue. I searched through the databases Medline, Embase and Pre‐Medline using the key words interleukin‐2 and interleukin‐2 receptor. I used recent reviews from these searches along with original articles on the subject. IL‐2 is a single polypeptide of molecular weight 15.5 kDa, 133 amino acid residues long. There is only a single IL‐2 gene locus in humans, on chromosome 4. IL‐2 is a globular protein containing two sets of α‐helical domains, lying at right angles to each other.2 These α‐helical regions are involved in the binding to the receptor, and indeed this helical …