High-affinity tcr for afp recognition
AssigneeXlifesc, Ltd.
InventorsYi LI, Liang CHEN
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Abstract
Provided in the present invention is a T-cell receptor (TCR) having the characteristic of binding a FMNKFIYEI-HLA A0201 complex; and the binding affinity of the TCR to the FMNKFIYEI-HLA A0201 complex is at least 5 times that of a wild-type TCR to the FMNKFIYEI-HLA A0201 complex. Further provided in the present invention is a fusion molecule of the TCR with a therapeutic agent. The TCR can be used alone or in combination with the therapeutic agent, so as to target a tumor cell presenting the FMNKFIYEI-HLA A0201 complex.
Claims28
A T cell receptor (TCR), which has 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:
- ATDEANDYKLS, and 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:
- SGDLS
- CDR2β:
- YYNGEE
- CDR3β:
- ASRGIGDAGELF
- the TCR α chain variable domain contains at least one of the following mutations:
- Residue before mutation
- Residue after mutation
- A at position 5 of CDR3α
- V or Q or Y or H or T or W or R or D or
- L or E
- N at position 6 of CDR3α
- Y or L or H or I or Q or F or M or W or
- T or A
- D at position 7 of CDR3α
- T or Q or E or R or A or H or M or W or
- K or S or G
- Y at position 8 of CDR3α
- P or A
- K at position 9 of CDR3α
- A or G
- S at position 11 of CDR3α
- Y
- and/or, the TCR β chain variable domain contains at least one of the following mutations:
- Residue before mutation
- Residue after mutation
- S at position 1 of CDR1β
- P or K
- L at position 4 of CDR1β
- I
- S at position 5 of CDR1β
- P or T
- Y at position 1 of CDR2β
- L
- N at position 3 of CDR2β
- A
- E at position 5 of CDR2β
- Y
- I at position 5 of CDR3β
- V or L
- A at position 8 of CDR3β
- S or G
- G at position 9 of CDR3β
- E or N or D.
- 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.
4-5. (canceled)
8-19. (canceled)
(canceled)
(canceled)
31-33. (canceled)
35-36. (canceled)
38-40. (canceled)
(canceled)
Dependencies are inferred from the claim text.