Advances in interleukin 2 receptor targeted treatment.
T cell activation and cellular immune responses are modulated by interleukin 2 (IL2) through binding to its corresponding cell surface receptor. Three forms of the receptor are recognised based on IL2 binding affinity. The high affinity receptor is a heterotrimer composed of alpha, beta, and gamma(c)-polypeptide chains. The 55 kDa alpha-chain also known as the Tac (T cell activation) antigen or CD-25 is a unique subunit of the high affinity IL2 receptor (IL2Ralpha). Resting T cells express few IL2Ralpha, however, when activated, the expression of ILR2alpha rapidly increases. The IL2Ralpha is shed from the cell surface and is measurable in the serum as a 45 kDa soluble form (s-Tac or s-IL2Ralpha). Serum concentrations of s-Tac can be used as a surrogate marker for T cell activation and IL2Ralpha expression. IL2Ralpha is over expressed by T cells in a number of autoimmune diseases, allograft rejection and a variety of lymphoid neoplasms. IL2 induced proliferation of T cells can be inhibited by the murine monoclonal antibody (anti-Tac) directed against the alpha-chain of the IL2R. Through molecular engineering, murine anti-Tac has been humanised reducing its immunogenicity without changing its specificity. Humanised anti-Tac (HAT) has been shown to reduce the incidence of renal and cardiac allograft rejection as well as decrease the severity of graft versus host disease in patients undergoing HLA matched allogeneic bone marrow transplantation. IL2Ralpha targeted treatment with radioimmunoconjugates of anti-Tac and immunotoxins has shown promise in the treatment of CD25 expressing lymphomas.
Morris
J C
JC
Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bldg 10, Rm 4N115, 10 Center Drive, Bethesda, MD 20892-1374, USA. jmorris@mail.nih.gov
Waldmann
T A
TA
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000628:therapy; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors* / Q000276:immunology
D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2