High affinity cell receptor for recognizing afp antigen
AssigneeXlifesc, Ltd.
InventorsYi LI, Xiaolin LI, Shaopei CHEN
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Abstract
Provided in the present invention is a T cell receptor (TCR) having the property of binding to a FMNKFIYEI-HLA A0201 complex; and the binding affinity of the TCR to the FMNKFIYEI-HLA A0201 complex is at least 2 times the binding affinity of the wild-type TCR to the FMNKFIYEI-HLA A0201 complex. Also provided in the present invention is a fusion molecule of such TCRs with therapeutic agents. Such TCRs can be used alone or in combination with therapeutic agents, so as to target tumor cells presenting the FMNKFIYEI-HLA A0201 complex.
Claims28
A T cell receptor (TCR) having an activity of binding to FMNKFIYEI-HLA A0201 complex, and the T cell receptor comprises a TCR α chain variable domain and a TCR β chain variable domain, the TCR α 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:
- TSINN
- CDR2α:
- IRSNERE
- CDR3α:
- ATDPRTGANSKLT,
- 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:
- ASEGLAYEQY,
- wherein the TCR α chain variable domain contains at least one of the following mutations:
- Residue before mutation
- Residue after mutation
- S at position 2 of CDR1α
- D or P or A or E
- I at position 3 of CDR1α
- V
- N at position 4 of CDR1α
- S or Y or D
- N at position 5 of CDR1α
- S or K
- R at position 5 of CDR3α
- A or S or V or D or E or Q or T
- T at position 6 of CDR3α
- M or R or L or A or N or S
- G at position 7 of CDR3α
- A or Q or S or E or N
- A at position 8 of CDR3α
- S or G or P or W
- N at position 9 of CDR3α
- S or T
- S at position 10 of CDR3α
- A or N or T or P
- and/or, the TCR β chain variable contains at least one of the following mutations:
- Residue before mutation
- Residue after mutation
- S at position 1 of CDR1β
- A or Q or G
- E at position 2 of CDR1β
- G or T or R or L
- H at position 3 of CDR1β
- W or R
- N at position 4 of CDR1β
- A or P
- Q at position 2 of CDR2β
- H
- N at position 3 of CDR2β
- G
- E at position 4 of CDR2β
- D
- A at position 5 of CDR2β
- M or L
- Q at position 6 of CDR2β
- E.
- and the α chain variable domain of the TCR comprises an amino acid sequence having at least 90% sequence homology with the amino acid sequence shown in SEQ ID NO:
- 1;
- and/or the β chain variable domain of the TCR comprises an amino acid sequence having at least 90% sequence homology with the amino acid sequence shown in SEQ ID NO:
- 2.
3-5. (canceled)
8-14. (canceled)
(canceled)
(canceled)
26-27. (canceled)
A TCR, wherein the TCR is selected from the group consisting of:
- Sequence of α chain
- Sequence of β chain
- TCR
- variable domain
- variable domain
- No.
- SEQ ID NO:
- SEQ ID NO:
- s-1
- 12
- 4
- s-2
- 10
- 4
- s-3
- 9
- 4
- s-4
- 11
- 4
- s-5
- 13
- 4
- s-6
- 14
- 4
- s-7
- 15
- 4
- s-8
- 16
- 4
- s-9
- 17
- 4
- s-10
- 18
- 4
- s-11
- 19
- 4
- s-12
- 20
- 4
- s-13
- 21
- 4
- s-14
- 3
- 36
- s-15
- 22
- 37
- s-16
- 23
- 38
- s-17
- 24
- 39
- s-18
- 25
- 39
- s-19
- 26
- 39
- s-20
- 26
- 38
- s-21
- 27
- 37
- s-22
- 28
- 40
- s-23
- 29
- 37
- s-24
- 29
- 41
- s-25
- 30
- 42
- s-26
- 31
- 41
- s-27
- 32
- 43
- s-28
- 26
- 44
- s-29
- 33
- 40
- s-30
- 24
- 42
- s-31
- 26
- 37
- s-32
- 30
- 45
- s-33
- 34
- 37
- s-34
- 30
- 39
- s-35
- 32
- 46
- s-36
- 35
- 42.
30-31. (canceled)
33-35. (canceled)
39-40. (canceled)
Dependencies are inferred from the claim text.