IL2RB binding molecules and methods of use
The present disclosure relates to biologically active molecules comprising a single domain antibody (sdAb) that specifically binds to the extracellular domain of IL2Rb, compositions comprising such antibodies, and methods of use thereof.
1. A IL2Rb binding molecule that specifically binds to the extracellular domain of IL2Rb, wherein the IL2Rb binding molecule comprises a single domain antibody (sdAb), and wherein the sdAb comprises a complementary determining region 1 (CDR1), a CDR2, and a CDR3 as shown in a row of the table below:
CDR1
CDR2
CDR3
YTYDTSDMS
DIDSGDWAAYADAVKG
SYWKWGKLNNF
(SEQ ID
(SEQ ID NO: 3)
(SEQ ID NO: 4)
NO: 2)
FTFSNYWIF
TSNTGGDTTKYADSVKG
GRCARSG
(SEQ ID
(SEQ ID NO: 7)
(SEQ ID NO: 8)
NO: 6)
FRFSNYGMS
YINGDGSRTHYADSVKG
GLSRDGWSLSAAS
(SEQ ID
(SEQ ID NO: 11)
(SEQ ID NO: 12)
NO: 10)
YTTYSFNYMG
VIYTGGGSTLYADSVKG
DDQRFASPLYAYFGY
(SEQ ID
(SEQ ID NO: 15)
(SEQ ID NO: 16)
NO: 14)
DTKSIRCMG
AIDREGFATYADSVYD
QNMCRVVRGAMTGVDY
(SEQ ID
(SEQ ID NO: 19)
(SEQ ID NO: 20)
NO: 18)
YTASRYCMA
AIHPGGGTTYYADSVKG
GSLWVPFGDRCAANY
(SEQ ID
(SEQ ID NO: 23)
(SEQ ID NO: 24)
NO: 22)
YEYCRIHMT
SIGSDGRKTYANSVTG
EYLYGLGCPDGSAY
(SEQ ID
(SEQ ID NO: 27)
(SEQ ID NO: 28)
NO: 26)
YTYSSYYCMG
AIDSDGSTSYADSVKG
SYEVVDCYPSGYGQDY
(SEQ ID
(SEQ ID NO: 31)
(SEQ ID NO: 32)
NO: 30)
2. The IL2Rb binding molecule of claim 1 , wherein the sdAb has at least 95% identity to a polypeptide sequence of any one of SEQ ID NOS:1, 5, 9, 13, 17, 21, 25, or 29.
3. A IL2Rb binding molecule that specifically binds to the extracellular domain of IL2Rb, wherein the IL2Rb binding molecule comprises a single domain antibody (sdAb), and wherein the sdAb comprises a complementary determining region 1 (CDR1), a CDR2, and a CDR3 as shown in a row of the table below:
CDR1
CDR2
CDR3
SEQ
SEQ
SEQ
CDR1
ID
CDR2
ID
CDR3
ID
AA Seq
NO:
AA Seq
NO:
AA Seq
NO:
FTFSLYDMS
42
GINSGGYSTYYAASA
43
RGLTSPYVIPNI
44
KG
KSFSDYPLG
46
HISWSGKLTYYRSTVK
47
MKLFNYGGRYCVLKPLTM
48
G
YQQ
RSFSGYAIG
50
VVSWRGSSTYYADSV
51
VPSGRSWYGRNRY
52
KG
RSINYYRMG
54
AIKWGGDGVYADSVK
55
MPLSSWSRGGYLEV
56
G
RFSWGNYAM
58
AIGRNSMATYYRDSA
59
KFMVADGWSRQYDY
60
Y
KG
RTFRRFMG
62
AINWPGGGTYYGDSV
63
TRKYNLYKFAD
64
KG
RIFNTYSMG
66
AIRWSGGTTYYTDSV
67
RVRLSNTALLQRY
68
KG
RTFGDYPIG
70
SISWGGSRQYYTDSV
71
RVRLSNTALLQRY
72
KG
RTFNSYAMG
74
VITWNSGRTYYADSV
75
APWAHNRE
76
KG
LTFRTYYMS
78
VISWIGSTTLYADSVK
79
NFLREGKREPRY
80
G
RIFNTYSMG
82
AIRWSGGTTYYTDSV
83
RVFARRY
84
KG
RTLSTYAMG
86
AIRWASGRTYYGDSV
87
RSRPYLNYGDFGY
88
KG
RTISTYAMV
90
VISRSGDRTYYADSVK
91
GGYTGIETITA
92
G
SIFNNNAVY
94
LITIGGRTGYADSVKG
95 5
GLKFGFNFYSKTAYDY
96
RIFNTYSMG
98
AIRWSGGTTYYTDSV
99
VPSGRSWYGRNRY
100
KG
RTFGYVAMG
102
SINWSGGSTAYADSV
103
STRFYIATMEQGSYDY
104
KG
RSFRSYAIG
106
AISYDGRRTYYGRSLK
107
HRSGTMFARYGMDY
108
D
RTFSSYAMG
110
AISRSGGYTSYADSVK
111
LIAPFYYGMDY
112
G
PTFTSYTMG
114
VISKGGRTYYADSVK
115
QRVGATSKYEYDY
116
G
FTFSTDWMY
118
LINTDGTSTSYTKSVK
119
GRTYWFYAMDY
120
G
RISNYAMG
122
VITRSGGSTYYADSVK
123
RRSQKLVTFGAEYPW
124
G
RTGTHYAMG
126
LILWNGEFTTYKDSVK
127
RVFARRY
128
G
FTFSNYWMY
130
HINTNGGNTYYRHSV
131
ANSDVGLGYYGMDY
132
KG
SIFNNNAVY
134
LITIGGRTGYADSVKG
135
RPGYWSSSYDY
136
RAPASYAMA
138
AINWSGRRTYYADSV
139
YLSGTYY
140
KG
LASSSFFMT
142
TISWTGRTSYYAASVK
143
YPRTLVRNREPIH
144
G
4. The IL2Rb binding molecule of claim 3 , wherein the sdAb has at least 95% identity to a polypeptide sequence of any one of SEQ ID NOS:41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, 105,109, 113, 117, 121, 125, 129, 133, 137 or 141.
5. The IL2Rb binding molecule of claim 1 , wherein the sdAb is humanized or otherwise comprises CDRs grafted onto a heterologous framework.
6. The IL2Rb binding molecule of claim 1 , further comprising a labeling agent, an imaging agent, and/or a therapeutic agent.
7. A method for isolating, depleting, or enriching IL2Rb+ cells a biological sample, comprising contacting the biological sample with the IL2Rb binding molecule of claim 1 .
8. A nucleic acid sequence encoding the IL2Rb binding molecule of claim 1 .
9. A recombinant viral or non-viral vector comprising a nucleic acid of claim 8 .
10. A host cell comprising a nucleic acid of claim 8 .
11. A pharmaceutical formulations comprising the viral or non-viral vector of claim 9 .
12. A kit comprising the IL2Rb binding molecule of claim 1 .
13. The IL2Rb binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:18, 19, and 20, respectively.
14. The IL2Rb binding molecule of claim 13 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:17.
15. The IL2Rb binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:30, 31, and 32, respectively.
16. The IL2Rb binding molecule of claim 15 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:29.
17. The IL2Rb binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:14, 15, and 16, respectively.
18. The IL2Rb binding molecule of claim 17 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:13.
19. The IL2Rb binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:10, 11, and 12, respectively.
20. The IL2Rb binding molecule of claim 19 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:9.
21. The IL2Rb binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:2, 3, and 4, respectively.
22. The IL2Rb binding molecule of claim 21 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:1.
23. The IL2Rb binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:6, 7, and 8, respectively.
24. The IL2Rb binding molecule of claim 23 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:5.
25. The IL2Rb binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:22, 23, and 24, respectively.
26. The IL2Rb binding molecule of claim 25 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:21.
27. The IL2Rb binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:26, 27, and 28, respectively.
28. The IL2Rb binding molecule of claim 27 , wherein the sdAb has at least 95% identity to a polypeptide sequence of SEQ ID NO:25.
29. The nucleic acid sequence of claim 8 , encoding the IL2Rb binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:18, 19, and 20, respectively.
30. The nucleic acid sequence of claim 8 , encoding the IL2Rb binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:30, 31, and 32, respectively.
31. The nucleic acid sequence of claim 8 , encoding the IL2Rb binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:14, 15, and 16, respectively.
32. The nucleic acid sequence of claim 8 , encoding the IL2Rb binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:10, 11, and 12, respectively.
33. The nucleic acid sequence of claim 8 , encoding the IL2Rb binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:2, 3, and 4, respectively.
34. The nucleic acid sequence of claim 8 , encoding the IL2Rb binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:6, 7, and 8, respectively.
35. The nucleic acid sequence of claim 8 , encoding the IL2Rb binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:22, 23, and 24, respectively.
36. The nucleic acid sequence of claim 8 , encoding the IL2Rb binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:26, 27, and 28, respectively.
37. The IL2Rb binding molecule of claim 1 , wherein the sdAb is linked to a second binding molecule that specifically binds to the extracellular domain of a second cell surface molecule.