IL-7R-α-γ binding compounds

1. An IL-7Rαγc ligand, wherein the IL-7Rαγc ligand comprises an amino acid sequence of Formula (6) (SEQ ID NO: 2125), an amino acid sequence of Formula (6a) (SEQ ID NO: 2126), an amino acid sequence of Formula (6b) (SEQ ID NO: 2127), an amino acid sequence of Formula (6c) (SEQ ID NO: 2128), an amino acid sequence of Formula (6d) (SEQ ID NO: 2129), an amino acid sequence of Formula (6e) (SEQ ID NO: 2130), an amino acid sequence of Formula (6f) (SEQ ID NO: 2131), or an amino acid sequence of Formula (6g) (SEQ ID NO: 2132):

(6)

-X 198 -X 199 -X 200 -I-P-W-C-T-L-D-P-G-X 210 -L-Q-C-A-W-

L-X 217 -X 218 -X 219 -X 400 -VVCQDWEGVELCWQ-

(6a)

-X 199 -X 200 -I-P-W-C-T-L-D-P-G-X 210 -L-Q-C-A-W-L-X 217 -

X 218 -X 219 -X 400 -VVCQDWEGVELCWQ-

(6b)

-X 200 -I-P-W-C-T-L-D-P-G-X 210 -L-Q-C-A-W-L-X 217 -

X 218 -X 219 -X 400 -VVCQDWEGVELCWQ-

(6c)

-I-P-W-C-T-L-D-P-G-X 210 -L-Q-C-A-W-L-X 217 -X 218 -

X 219 -X 400 -VVCQDWEGVELCWQ-

(6d)

-X 198 -X 199 -X 200 -I-P-W-C-T-L-D-P-G-X 210 -L-Q-C-A-W-

L-X 217 -X 218 -X 400 -VVCQDWEGVELCWQ-

(6e)

-X 198 -X 199-X200 -I-P-W-C-T-L-D-P-G-X 210 -L-Q-C-A-W-

L-X 217 -X 400 -VVCQDWEGVELCWQ-

(6f)

-X 198 -X 199 -X 200 -I-P-W-C-T-L-D-P-G-X 210 -L-Q-C-

A-W-L-X 400 -VVCQDWEGVELCWQ-

(6g)

-X 198 -X 199 -X 200 -I-P-W-C-T-L-D-P-G-X 210 -L-Q-C-

A-W-L-X 400 -VVCQDWEGVELCWQ-

wherein,

X 198 is selected from A, G, P, S, T, and V;

X 199 is selected from F, H, W, and Y;

X 200 is selected from A, G, H, K, P, R, S, and T;

X 210 is selected form A, G, P, S, and T;

X 217 is selected from A, G, H, K, P, R, S, and T;

X 218 is selected from an amino acid and a single bond;

X 219 is selected from an amino acid and a single bond; and

X 400 is selected from (G)n (SEQ ID NO: 9390), (GS)n (SEQ ID NO: 9391), (GGS)n (SEQ ID NO: 9392), (GGGS)n (SEQ ID NO: 9393), (GGGGS)n (SEQ ID NO: 9394), and a combination of any of the foregoing, wherein n is an integer from 1 to 5.

2. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises any one of SEQ ID NO: 2110-2124:

SEQ ID NO: 2110

VHRIPWCTLDPGGLQCAWLRQM-X 400 -VVCQDWEGVELCWQ

SEQ ID NO: 2111

VHRIPWCTLDPGGLQCAWLRQ-X 400 -VVCQDEGVELCWQ

SEQ ID NO: 2112

VHRIPWCTLDPGGLQCAWLR-X 400 -VVCQDWGVELCWQ

SEQ ID NO: 2113

VHRIPWCTLDPGGLQCAWLGKH-X 400 -VVCQWEGVELCWQ

SEQ ID NO: 2114

VHRIPWCTLDPGGLQCAWLRM-X 400 -VVCQDWGVELCWQ

SEQ ID NO: 2115

GWGIPWCTLDPGGLQCAWLRQM-X 400 -VVCQDWEGVELCWQ

SEQ ID NO: 2116

GWGIPWCTLDPGGLQCAWLRQ-X 400 -VVCQDEGVELCWQ

SEQ ID NO: 2117

GWGIPWCTLDPGGLQCAWLR-X 400 -VVCQDWGVELCWQ

SEQ ID NO: 2118

GWGIPWCTLDPGGLQCAWLGKH-X 400 -VVCQWEGVELCWQ

SEQ ID NO: 2119

GWGIPWCTLDPGGLQCAWLRM-X 400 -VVCQDWGVELCWQ

SEQ ID NO: 2120

IPWCTLDPGGLQCAWLRQM-X 400 -VVCQDWEGVELCWQ

SEQ ID NO: 2121

IPWCTLDPGGLQCAWLRQ-X 400 -VVCQDEGVELCWQ

SEQ ID NO: 2122

IPWCTLDPGGLQCAWLR-X 400 -VVCQDWGVELCWQ

SEQ ID NO: 2123

IPWCTLDPGGLQCAWLGKH-X 400 -VVCQWEGVELCWQ

SEQ ID NO: 2124

IPWCTLDPGGLQCAWLRM-X 400 -VVCQDWGVELCWQ

wherein X 400 is selected from (G)n (SEQ ID NO: 9390), (GS)n (SEQ ID NO: 9391), (GGS)n (SEQ ID NO: 9392), (GGGS)n (SEQ ID NO: 9393), (GGGGS)n (SEQ ID NO: 9394), and a combination of any of the foregoing, wherein n is an integer from 1 to 5.

3. The IL-7Rαγc ligand of claim 2 , wherein X 400 is selected from -GGGGSGG-, -GG-GGGGS-GG-, and -G-GGGGS-GG-.

4. The IL-7Rαγc ligand of claim 2 , wherein X 400 is -GGGGSGG-.

5. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises any one of SEQ ID NO: 2091, 2096-2109, and 2064-2073:

SEQ ID NO: 2091

VHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQ

SEQ ID NO: 2096

VHRIPWCTLDPGGLQCAWLRQGGGGSGGVVCQDEGVELCWQ

SEQ ID NO: 2097

VHRIPWCTLDPGGLQCAWLRGGGGSGGVVCQDWGVELCWQ

SEQ ID NO: 2098

VHRIPWCTLDPGGLQCAWLGKHGGGGSGGVVCQWEGVELCWQ

SEQ ID NO: 2099

VHRIPWCTLDPGGLQCAWLRMGGGGSGGVVCQDWGVELCWQ

SEQ ID NO: 2100

GWGIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQ

SEQ ID NO: 2101

GWGIPWCTLDPGGLQCAWLRQGGGGSGGVVCQDEGVELCWQ

SEQ ID NO: 2102

GWGIPWCTLDPGGLQCAWLRGGGGSGGVVCQDWGVELCWQ

SEQ ID NO: 2103

GWGIPWCTLDPGGLQCAWLGKHGGGGSGGVVCQWEGVELCWQ

SEQ ID NO: 2104

GWGIPWCTLDPGGLQCAWLRMGGGGSGGVVCQDWGVELCWQ

SEQ ID NO: 2105

IPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQ

SEQ ID NO: 2106

IPWCTLDPGGLQCAWLRQGGGGSGGVVCQDEGVELCWQ

SEQ ID NO: 2107

IPWCTLDPGGLQCAWLRGGGGSGGVVCQDWGVELCWQ

SEQ ID NO: 2108

IPWCTLDPGGLQCAWLGKHGGGGSGGVVCQWEGVELCWQ

SEQ ID NO: 2109

IPWCTLDPGGLQCAWLRMGGGGSGGVVCQDWGVELCWQ

SEQ ID NO: 2064

VHRIPWCTLDPGGLQCAWLRQMGGGGSGGVVCQDWEGVELCWQPPA

SEQ ID NO: 2065

VHRIPWCTLDPGGLQCAWLRQGGGGSGGVVCQDWEGVELCWQPPA

SEQ ID NO: 2066

VHRIPWCTLDPGGLQCAWLRGGGGSGGVVCQDWEGVELCWQPPA

SEQ ID NO: 2067

VHRIPWCTLDPGGLQCAWLGKHGGGGSGGVVCQDWEGVELCWQPPA

SEQ ID NO: 2068

VHRIPWCTLDPGGLQCAWLRQGGGGGSGGVVCQDWEGVELCWQPPA

SEQ ID NO: 2069

VHRIPWCTLDPGGLQCAWLRGGGGGGSGGVVCQDWEGVELCWQPPA

SEQ ID NO: 2070

VHRIPWCTLDPGGLQCAWLRQGGGGSGGVVCQDWEGVELCWQGG

SEQ ID NO: 2071

VHRIPWCTLDPGGLQCAWLRGGGGSGGVVCQDWEGVELCWQGG

SEQ ID NO: 2072

GWGIPWCTLDPGSLQCAWLGKHGGGGSGGVVCQDWEGVELCWQGG

SEQ ID NO: 2073

VHRIPWCTLDPGGLQCAWLRQM(PA)8GVVCQDWEGVELCWQGG.

6. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises (G)n bonded to the N-terminus, the C-terminus, or both the N-terminus and the C-terminus, wherein n is independently selected from 1 to 5.

7. The IL-7Rαγc ligand of claim 1 , wherein the IL-7Rαγc ligand comprises SEQ ID NO: 2072.

8. A compound comprising the IL-7Rαγc ligand of claim 1 .

9. The compound of claim 8 , wherein the compound comprises the IL-7Rαγc ligand bound to a construct partner through a construct linker.

10. The compound of claim 9 , wherein the construct linker comprises (G)n (SEQ ID NO: 9380), (GS)n (SEQ ID NO: 9381), (GGS)n (SEQ ID NO: 9382), (GGGS)n (SEQ ID NO: 9383), (GGGGS)n (SEQ ID NO: 9384), or a combination of any of the foregoing, wherein n is an integer from 1 to 20.

11. The compound of claim 9 , wherein the construct linker comprises (P) n (SEQ ID NO: 9420), (PA) n (SEQ ID NO: 9421), or a combination thereof, wherein n is an integer from 1 to 20.

12. The compound of claim 9 , wherein the construct partner comprises a protein.

13. The compound of claim 9 , wherein the compound comprises a tumor targeting moiety.

14. The compound of claim 13 , wherein the tumor targeting moiety comprises 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.

15. The compound of claim 9 , wherein the construct partner comprises a polymer, a polypeptide, an Fc-fragment, an immunoglobulin fragment, and an antibody, a vaccine, a viral surface antigen, or a virus like particle.

16. The compound of claim 9 , wherein the construct partner comprises an Fc fragment.

17. The compound of claim 16 , wherein the Fc fragment comprises an IgG1 immunoglobulin Fc fragment, an IgG2 immunoglobulin Fc fragment, or an IgG4 immunoglobulin Fc fragment.

18. The compound of claim 9 , wherein the construct partner comprises an IgG Fc-fragment, wherein the IL-7Rαγc ligand is bound to one or both CH3 domains of the IgG Fc-fragment.

19. The compound of claim 18 , wherein the N-terminus of the IL-7Rαγc ligand is bound to the C-terminus of the CH3 domain of the IgG Fc-fragment through the construct linker.

20. The compound of claim 18 , wherein the IL-7Rαγc ligand comprises SEQ ID NO: 2072.

21. The compound of claim 18 , wherein the construct linker comprises (GS)n (SEQ ID NO: 9381) and n is an integer from 1 to 20.

22. The compound of claim 18 , wherein the construct linker comprises (GS)10.

23. A pharmaceutical composition comprising the IL-7Rαγc ligand claim 1 .

24. The pharmaceutical composition of claim 23 , further comprising a chemotherapeutic agent, an immunomodulator, a checkpoint inhibitor, a vaccine, or a combination of any of the foregoing.

25. A pharmaceutical composition comprising the compound of claim 8 .

26. The pharmaceutical composition of claim 25 , further comprising a chemotherapeutic agent, an immunomodulator, a checkpoint inhibitor, a vaccine, or a combination of any of the foregoing.

27. A nucleic acid encoding for the IL-7Rαγc ligand of claim 1 .

28. A nucleic acid encoding for the compound of claim 8 .