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. 2000 Nov;59(Suppl 1):i109–i114. doi: 10.1136/ard.59.suppl_1.i109

Advances in interleukin 2 receptor targeted treatment

J Morris, T Waldmann
PMCID: PMC1766615  PMID: 11053100

Abstract

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 α, β, and γc-polypeptide chains. The 55 kDa α-chain also known as the Tac (T cell activation) antigen or CD-25 is a unique subunit of the high affinity IL2 receptor (IL2Rα). Resting T cells express few IL2Rα, however, when activated, the expression of ILR2α rapidly increases. The IL2Rα is shed from the cell surface and is measurable in the serum as a 45 kDa soluble form (s-Tac or s-IL2Rα). Serum concentrations of s-Tac can be used as a surrogate marker for T cell activation and IL2Rα expression. IL2Rα 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 α-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. IL2Rα targeted treatment with radioimmunoconjugates of anti-Tac and immunotoxins has shown promise in the treatment of CD25 expressing lymphomas.



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Selected References

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