High-affinity t cell receptor against prame
AssigneeGuangdong Xiangxue Life Sciences, Ltd.
InventorsYi LI, Jinhua HUANG, Kai ZHAN
Life of this patent
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Abstract
Provided is a T cell receptor (TCR) having a feature of binding to a VLDGLDVLL-HLA A2 complex. The binding affinity of the TCR to the VLDGLDVLL-HLA-A0201 complex is at least 2 times of the binding affinity of a wild-type TCR to the VLDGLDVLL-HLA-A0201 complex. Also provided is a fusion molecule of the TCR and a therapeutic agent. The TCR can be used alone or in combination with a therapeutic agent to target a tumor cell presenting the VLDGLDVLL-HLA-A0201 complex.
Claims19
1-60. (canceled)
A T cell receptor (TCR), which has an activity of binding to VLDGLDVLL-HLA-A0201 complex, the T cell receptor comprises a TCR α chain variable domain and a TCR β chain variable domain, the α chain variable domain of the TCR comprises an amino acid sequence having at least 90% of sequence homology with the amino acid sequence shown in SEQ ID NO:
- 1, and the β chain variable domain of the TCR comprises an amino acid sequence having at least 90% of sequence homology with the amino acid sequence shown in SEQ ID NO:
- 2, the TCRα chain variable domain comprises three CDR regions, and the reference sequences of the three CDR regions of the TCR α chain variable domain are listed as follows,
- CDR1α:
- DRGSQS
- CDR2α:
- IYSNGD
- CDR3α:
- AVARTYTGNQFY,
- the TCR β chain variable domain comprises three CDR regions, and the reference sequences of the three CDR regions of the TCR β chain variable domain are listed as follows,
- CDR1β:
- SEHNR
- CDR2β:
- FQNEAQ
- CDR3β:
- ASSSQKFSGIQPQH,
- and the TCRα chain variable domain contains at least one of the following mutations:
- Residue before mutation
- Residue after mutation
- S at position 4 of CDR1α
- T or A
- S at position 6 of CDR1α
- A
- I at position 1 of CDR2α
- Q or L or T
- Y at position 2 of CDR2α
- V
- S at position 3 of CDR2α
- M or V or Q
- N at position 4 of CDR2α
- P or D
- A at position 3 of CDR3α
- V
- R at position 4 of CDR3α
- L
- T at position 5 of CDR3α
- S
- Y at position 6 of CDR3α
- W
- T at position 7 of CDR3α
- K or A or R or L or Q or F
- G at position 8 of CDR3α
- S
- N at position 9 of CDR3α
- T
- Q at position 10 of CDR3α
- G or R
- and/or, the TCR β chain variable domain contains at least one of the following mutations:
- Residue before mutation
- Residue after mutation
- N at position 3 of CDR2β
- D or G
- E at position 4 of CDR2β
- S or R
- A at position 5 of CDR2β
- I or S
- Q at position 6 of CDR2β
- E
- S at position 3 of CDR3β
- N
- S at position 4 of CDR3β
- A or P or N or K or Q or T or M or R
- Q at position 5 of CDR3β
- S or G or T
- K at position 6 of CDR3β
- P or G or L
- F at position 7 of CDR3β
- V or L.
A TCR, wherein the TCR is selected from the group consisting of:
- Sequence of α chain variable
- Sequence of β chain variable
- TCR No.
- domain SEQ ID NO:
- domain SEQ ID NO:
- s-1
- 9
- 4
- s-2
- 10
- 4
- s-3
- 11
- 4
- s-4
- 12
- 4
- s-5
- 13
- 4
- s-6
- 14
- 4
- s-7
- 15
- 4
- s-8
- 3
- 35
- s-9
- 3
- 36
- s-10
- 3
- 37
- s-11
- 3
- 38
- s-12
- 3
- 39
- s-13
- 3
- 40
- s-14
- 3
- 41
- s-15
- 3
- 42
- s-16
- 3
- 43
- s-17
- 3
- 44
- s-18
- 16
- 45
- s-19
- 17
- 46
- s-20
- 18
- 47
- s-21
- 19
- 48
- s-22
- 20
- 49
- s-23
- 21
- 45
- s-24
- 22
- 47
- s-25
- 23
- 50
- s-26
- 24
- 45
- s-27
- 25
- 45
- s-28
- 26
- 51
- s-29
- 27
- 50
- s-30
- 28
- 50
- s-31
- 29
- 52
- s-32
- 30
- 49
- s-33
- 31
- 50
- s-34
- 32
- 45
- s-35
- 33
- 47
- s-36
- 34
- 49.
Dependencies are inferred from the claim text.