IL2RG 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 human IL2Rg, compositions comprising such antibodies, and methods of use thereof.
1. An IL2Rg binding molecule that specifically binds to the extracellular domain of IL2Rg, wherein the IL2Rg 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
FTFDDSDMG
TISSDGSTYYADSVKG
DFMIAIQAPGAGC
(SEQ ID NO: 2)
(SEQ ID NO: 3)
(SEQ ID NO: 4)
FSFSSYPMT
TIASDGGSTAYAASVEG
GYGDGTPA
(SEQ ID NO: 6)
(SEQ ID NO: 7)
(SEQ ID NO: 8)
FTFDDREMN
TISSDGSTYYADSVKG
DFMIAIQAPGAGC
(SEQ ID NO: 10)
(SEQ ID NO: 11)
(SEQ ID NO: 12)
FTFDDSDMG
TISSDGNTYYTDSVKG
EPRGYYSNYGGRREC
(SEQ ID NO: 14)
(SEQ ID NO: 15)
NY
(SEQ ID NO: 16)
FSFSSYPMT
TIASDGGSTAYAASVEG
GYGDGTPA
(SEQ ID NO: 18)
(SEQ ID NO: 19)
(SEQ ID NO: 20)
FTFSNAHMS
SIYSGGSTWYADSVKG
NRLHYYSDDDSL
(SEQ ID NO: 22)
(SEQ ID NO: 23)
(SEQ ID NO: 24)
FTFDDREMN
TISSDGSTYYADSVKG
DFMIAIQAPGAGC
(SEQ ID NO: 26)
(SEQ ID NO: 27)
(SEQ ID NO: 28)
YTFSSYCMG
ALGGGSTYYADSVKG
AWVACLEFGGSWYDL
(SEQ ID NO: 30)
(SEQ ID NO 31)
(SEQ ID NO 32)
ARYKH
FTFDDSDMG
TISSDGSTYYADSVKG
EPRGYYSNYGGRREC
(SEQ ID NO 34)
(SEQ ID NO 35)
NY
(SEQ ID NO 36)
SIYSSAYIG
GIYTRDGSTAYADSVKG
GRRTKSYVYIFRPEE
(SEQ ID NO 38)
(SEQ ID NO 39)
YNY
(SEQ ID NO 40)
FTFSSAHMS
SIYSGGGTFYADSVKG
NRLHYYSDDDSL
(SEQ ID NO 42)
(SEQ ID NO 43)
(SEQ ID NO 44)
FTFSNAHMS
SIYSGGSTWYADSVKG
NRLHYYSDDDSL
(SEQ ID NO 46)
(SEQ ID NO 47)
(SEQ ID NO 48)
FIFDDSDMG
TISSDGSTYYADSVKG
EPRGYYSNYGGRREC
(SEQ ID NO 50)
(SEQ ID NO 51)
NY
(SEQ ID NO 52)
FTADDSDMG
TISSDGSTYYADSVKG
EPRGYYSNYGGRREC
(SEQ ID NO 54)
(SEQ ID NO 55)
NY
(SEQ ID NO 56)
FTFSSAHMS
SIYSGGGTFYADSVKG
NRLHYYSDDDSL
(SEQ ID NO 58)
(SEQ ID NO 59)
(SEQ ID NO 60)
FTFSNAHMS
SIYSGGSTWYADSVKG
NRLHYYSDDDSL
(SEQ ID NO 62)
(SEQ ID NO 63)
(SEQ ID NO 64)
FTFSNAHMS
SIYSGGSTWYADSVKG
NRLHYYSDDDSL
(SEQ ID NO 66)
(SEQ ID NO 67)
(SEQ ID NO 68
FTFSSYPMT
TIASDGGSTAYAASVEG
GYGDGTPA
(SEQ ID NO 70)
(SEQ ID NO 71)
(SEQ ID NO 72)
FTFDDREMN
TISSDGSTYYADSVKG
DFMIAIQAPGAGC
(SEQ ID NO 74)
(SEQ ID NO 75)
(SEQ ID NO 76)
FTFDDSDMG
TISSDGSTYYADSVKG
EPRGYYSNYGGRREC
(SEQ ID NO 78)
(SEQ ID NO 79)
NY
(SEQ ID NO 80)
YTSCMG
TIYTRGRSIYYADSVKG
GGYSWSAGCEFNY
(SEQ ID NO 82)
(SEQ ID NO 83)
(SEQ ID NO 84)
FSFSSYPMT
TIASDGGSTAYAASVEG
GYGDGTPA
(SEQ ID NO 86)
(SEQ ID NO 87)
(SEQ ID NO 88)
FSFSSYPMT
TIASDGGSTAYAASVEG
GYGDGTPA
(SEQ ID NO 90)
(SEQ ID NO 91)
(SEQ ID NO 92).
2. The IL2Rg binding molecule of claim 1 , wherein the sdAb has at least 95% amino acid sequence identity to a polypeptide sequence of any one of SEQ ID NOS: 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, or 89.
3. An IL2Rg binding molecule that specifically binds to the extracellular domain of IL2Rg, wherein the IL2Rg 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
CDR1
CDR2
CDR2
CDR3
CDR3
AA Seq
SEQ ID
AA Seq
SEQ ID
AA Seq
SEQ ID
STYANYLMG
121
AIYSGGGSTYYADSVKG
122
ASAVKGDKGDIVVVVTGTQRMEYDY
123
FTFDESVMS
125
IISSDDNTYYDDSVKG
126
RRRRPVYDSDYELRPRPLCGDFGV
127
LPFDEDDMG
129
SISSDGTAYYADSVKG
130
GVHRQFGGSSSCGDAFYGMDY
131
DVYGRNSMA
133
VGYSVVTTTYYADSVKG
134
DGNLWRGLRPSEYTY
135
FPYSRYCMG
137
AIEPDGSTSYADSVKG
138
DERCFYLKDYDLRRPAQYRY
139
FTFDESDMG
141
VITSDDNPYYDDSVKG
142
RSRQPVYSRDYELRPRPLCGDFGV
143
FTFDDFDMG
145
TISDDGSTYYADSVKG
146
EGALGSKTNCGWVGNFGY
147
FTFDDFDMG
149
TISDDGSTYYADSVKG
150
EGALGSKTNCGWVGNFGY
151
FTFDDFDMG
153
TISDDGSTYYADSVKG
154
EGALGSKTNCGWVGNFGY
155
FTFSDRDMG
157
TISDDGSTYYADSVKG
158
EGALGSKTNCGWVGNFGY
159
YGYNYIG
161
VIYIGGGDTYYADSVKG
162
RYCVGSVYACLRGGHDEYAH
163
YGYNYIG
165
VIYTGGGDTYYADSVKG
166
RYCVGSVYACLRGGHDEYAH
167
FTFDDFDMG
169
TISDDGSTYYANSVKG
170
EGALGSKTNCGWVGNFGY
171
FTFDDFDMG
173
TISDDGSTYYADSVKG
174
EGALGSKMNCGWVGNFGY
175.
4. The IL2Rg binding molecule of claim 3 , wherein the sdAb has at least 95% amino acid sequence identity to a polypeptide sequence of any one of SEQ ID NOS: 116, 120, 124, 128, 132, 136, 140, 144, 148, 152, 156, 160, 164 168, or 172.
5. The IL2Rg binding molecule of claim 1 , wherein the sdAb is humanized or otherwise comprises CDRs grafted onto a heterologous framework.
6. The IL2Rg binding molecule of claim 1 , further comprising one or more of a labeling agent, an imaging agent, and a therapeutic agent.
7. A method for isolating, depleting, or enriching IL2Rg+ cells in a biological sample, comprising contacting the biological sample with the IL2Rg binding molecule of claim 1 .
8. A nucleic acid sequence encoding the IL2Rg 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 IL2Rg binding molecule of claim 1 .
13. The IL2Rg binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:86, 87, and 88, respectively.
14. The IL2Rg binding molecule of claim 13 , wherein the sdAb has at least 95% amino acid sequence identity to a polypeptide sequence of SEQ ID NO:85.
15. The IL2Rg binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:74, 75, and 76, respectively.
16. The IL2Rg binding molecule of claim 15 , wherein the sdAb has at least 95% amino acid sequence identity to a polypeptide sequence of SEQ ID NO:73.
17. The IL2Rg binding molecule of claim 1 , wherein the sdAb comprises the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:78, 79, and 80, respectively.
18. The IL2Rg binding molecule of claim 17 , wherein the sdAb has at least 95% amino acid sequence identity to a polypeptide sequence of SEQ ID NO:77.
19. The nucleic acid sequence of claim 8 , encoding the IL2Rg binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:86, 87, and 88, respectively.
20. The nucleic acid sequence of claim 8 , encoding the IL2Rg binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:74, 75, and 76, respectively.
21. The nucleic acid sequence of claim 8 , encoding the IL2Rg binding molecule comprising the sdAb having the CDR1, the CDR2, and the CDR3 of SEQ ID NOS:78, 79, and 80, respectively.
22. The IL2Rg 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.