IL-2alpha receptor subunit binding compounds
Peptidyl IL-2Rα ligands and compounds comprising the IL-2Rα ligands are disclosed. The IL-2Rα ligands and compounds such as synthetic monomers, homodimers, or heteromers and recombinant fusion proteins comprising the IL-2Rα ligands can be used as targeting or imaging agents, as diagnostics or to treat cancers and autoimmune diseases.
1. An IL-2Rα ligand, wherein the IL-2Rα ligand comprises an amino acid sequence of Formula (20a) (SEQ ID NO: 235) or Formula (20b) (SEQ ID NO: 236), wherein the IL-2Rα ligand binds to the human IL-2Rα subunit with an IC 50 of less than 100 μM:
-X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 - (20a)
-X 1 -C-X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -C-X 14 - (20b)
wherein,
X 1 is W;
X 2 is C;
X 3 is selected from F, I, L, M, V, W, and Y;
X 4 is G;
X 5 is Q;
X 6 is P;
X 7 is L;
X 8 is selected from F, I, L, M, V, W, and Y;
X 9 is R;
X 10 is selected from H, N, Q, F, I, L, M, V, W, and Y;
X 11 is G;
X 12 is S;
X 13 is C; and
X 14 is K.
2. The IL-2Rα ligand of claim 1 , wherein the amino acid sequence independently comprises from 1 to 4 glycines (G) on the N-terminus, on the C-terminus, or on both the N- and C-termini.
3. A compound comprising the IL-2Rα ligand of claim 1 .
4. The compound of claim 3 , wherein the compound comprises an antibody or an IgG fragment.
5. The compound of claim 3 , wherein the compound comprises a tumor-targeting moiety, an immune-cell targeting moiety, or a combination thereof.
6. The compound of claim 3 , wherein the compound comprises an IL-2Rβ ligand, an IL-2Rγc ligand, or both an IL-2Rβ ligand and an IL-2Rγc ligand.
7. A pharmaceutical composition comprising the IL-2Rα ligand of claim 1 .
8. A pharmaceutical composition comprising the compound of claim 3 .
9. The IL-2Rα ligand of claim 1 , wherein X 3 is selected from I and V.
10. The IL-2Rα ligand of claim 1 , wherein X 8 is selected from F and Y.
11. The IL-2Rα ligand of claim 1 , wherein X 10 is selected from F, I, L, M, N, Q, V, W, and Y.
12. The IL-2Rα ligand of claim 1 , wherein X 10 is selected from L and Q.
13. The IL-2Rα ligand of claim 1 , wherein X 1 is W, X 2 is C, X 4 is G, X 5 is Q, X 6 is P, X 7 is L, X 9 is R, X 11 is G, X 12 is S, X 13 is C, and X 14 is K.
14. An IL-2Rα ligand, wherein the IL-2Rα ligand comprises an amino acid sequence of Formula (20a) (SEQ ID NO: 235) or Formula (20b) (SEQ ID NO: 236), wherein the IL-2Rα ligand binds to the human IL-2Rα subunit with an IC 50 of less than 100 μM:
-X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 - (20a)
-X 1 -C-X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -C-X 14 - (20b)
wherein,
X 1 is W;
X 2 is C;
X 3 is selected from I and V;
X 4 is G;
X 5 is Q;
X 6 is P;
X 7 is L;
X 8 is selected from F and Y;
X 9 is R;
X 10 is selected from F, H, I, L, M, N, Q, S, T, V, W, and Y;
X 11 is G;
X 12 is S;
X 13 is C; and
X 14 is K.
15. A compound comprising the IL-2Rα ligand of claim 14 .
16. The compound of claim 15 , wherein the compound comprises an antibody or an IgG fragment.
17. The compound of claim 15 , wherein the compound comprises a tumor-targeting moiety, an immune-cell targeting moiety, or a combination thereof.
18. The compound of claim 15 , wherein the compound comprises an IL-2Rβ ligand, an IL-2Rγc ligand, or both an IL-2Rβ ligand and an IL-2Rγc ligand.
19. A pharmaceutical composition comprising the IL-2Rα ligand of claim 14 .
20. A pharmaceutical composition comprising the compound of claim 15 .