IL-2RGAMMA BINDING COMPOUNDS
IL-2Rβ ligands and IL-2Rγc ligands and compounds comprising the ligands are disclosed. The ligands and compounds such as heterodimers and fusion proteins comprising the IL-2Rβ ligands and/or the IL-2Rγc ligands can be IL-2 receptor agonists.
1 . An IL-2Rγc ligand comprising an amino acid sequence:
—X 174 —X 175 —C—X 176 —X 177 —X 178 —X 179 —X 180 —X 181 —X 182 —X 183 —C—X 184 —X 185 —
wherein,
X 174 is selected from F, I, L, M, V, W, and Y;
X 175 is selected from D, E, F, I, L, M, V, W, and Y;
X 176 is selected from D, E, H, N, Q, S, T, and Y;
X 177 is selected from D and E;
X 178 is selected from F, H, I, L, M, V, W, and Y;
X 179 is selected from an amino acid comprising an acidic side chain or a polar/neutral side chain;
X 180 is G;
X 181 is V;
X 182 is E;
X 183 is L;
X 184 is W; and
X 185 is selected from F, I, L, M, V, W, and Y.
2 . The IL-2Rγc ligand of claim 1 , wherein X 174 is V.
3 . The IL-2Rγc ligand of claim 1 , wherein X 175 is selected from D and E.
4 . The IL-2Rγc ligand of claim 1 , wherein X 175 is selected from F, I, L, M, V, W, and Y.
5 . The IL-2Rγc ligand of claim 1 , wherein X 176 is selected from E and Q.
6 . The IL-2Rγc ligand of claim 1 , wherein X 179 is selected from D, E, H, N, Q, S, T, and Y.
7 . The IL-2Rγc ligand of claim 1 , wherein X 178 is selected from F, H, I, L, M, V, W, and Y.
8 . The IL-2Rγc ligand of claim 1 , wherein X 178 is selected from F, H, W, and Y.
9 . The IL-2Rγc ligand of claim 1 , wherein X 178 is W.
10 . The IL-2Rγc ligand of claim 1 , wherein X 179 is selected from D, E, and Q.
11 . The IL-2Rγc ligand of claim 1 , wherein X 185 is L.
12 . The IL-2Rγc ligand of claim 1 , wherein,
X 174 is selected from I and V;
X 175 is selected from E, I, L, M, and V;
X 176 is selected from D, E, and Q;
X 177 is selected from D and E;
X 178 is selected from F and W;
X 179 is selected from D, E, and Q;
X 180 is G;
X 181 is V;
X 182 is E;
X 183 is L;
X 184 is W; and
X 185 is selected from I, L, and V.
13 . The IL-2Rγc ligand of claim 1 , wherein,
X 174 is V;
X 175 is selected from D, E, F, I, L, M, V, W, and Y;
X 176 is selected from D, E, H, N, Q, S, T, and Y;
X 177 is selected from D and E;
X 178 is W;
X 179 is selected from D, E, and Q;
X 180 is G;
X 181 is V;
X 182 is E;
X 183 is L;
X 184 is W; and
X 185 is selected from F, I, L, M, V, W, and Y.
14 . A compound comprising an IL-2Rγc ligand of claim 1 .
15 . The compound of claim 14 , wherein the compound is selected from a polymer, an antibody, a conjugate, and a fusion protein.
16 . The compound of claim 15 , wherein, the fusion protein comprises an IgG molecule, an IgG Fab fragment, or an Fc fragment.
17 . The compound of claim 14 , wherein the compound comprises an IL-2Rα ligand, an IL-2Rβ ligand, or both an IL-2Rα ligand and an IL-2Rβ ligand.
18 . The compound of claim 14 , wherein the compound comprises a tumor-targeting moiety selected from, a tumor-specific antibody, a tumor-specific antibody fragment, a tumor-specific protein, a tumor-specific peptide, a non-peptidyl tumor cell ligand, or a combination of any of the foregoing.
19 . The compound of claim 14 , wherein the compound comprises an immune cell-targeting moiety selected from an immune cell-specific antibody, an immune cell-specific antibody fragment, an immune cell-specific protein, an immune cell-specific peptide, a non-peptidyl immune cell-ligand, or a combination of any of the foregoing.
20 . A pharmaceutical composition comprising the IL-2Rγc ligand of claim 1 .
21 . A pharmaceutical composition comprising the compound of claim 14 .