| 摘要 |
PURPOSE: Disclosed is a T-cell selective interleukin-4 agonists, thereby it realizes a less toxic IL-4 mutant that allows greater therapeutic use of this interleukin. CONSTITUTION: Directed is to human IL-4 muteins numbered in accordance with wild-type IL-4 having T-cell activating activity, but having reduced endothelial cell activating activity. In particular, related is to human IL-4 muteins wherein the surface-exposed residues of the D helix of the wild-type IL-4 are mutated whereby the resulting mutein causes T-cell proliferation, and causes reduced IL-6 secretion from HUVECs, relative to wild-type IL-4. Further, disclosed is to IL-4 muteins having single, double and triple mutations represented by the designators R121A, R121D, R121E, R121F, R121H, R121I, R121K, R121N, R121P, R121T, R121W; Y124A, Y124Q, Y124R, Y124S, Y124T; Y124A/S125A, T13D/R121E; and R121T/E122F/Y124Q, when numbered in accordance with wild-type IL-4 (His=1). Disclosed is a poly nucleotides coding for the muteins, vectors containing the poly nucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment. |
