PD-L1 binding polypeptide or composite
The present invention relates to the field of medical biology, and discloses a high-resolution crystal structure of a complex of PD-L1-blocking heavy-chain single-domain antibody KN035 binding with PD-L1, and the use of the crystal structure. The invention also relates to novel PD-L1 binding polypeptides or compounds developed based on the crystal structure and uses thereof.
1. An isolated polypeptide comprising an amino acid sequence set forth in SEQ ID NO: 4, which is capable of specifically binding to human PD-L1 and blocking the interaction of PD-L1 and PD1,
wherein the polypeptide does not comprise the amino acid sequence of SEQ ID NO: 2 and/or SEQ ID NO: 3, and
wherein the polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 10, 12, 16-18, 20, and/or 23.
2. A method of producing a polypeptide that binds to PD-L1 and an additional target, comprising replacing the CDR1 and/or the CDR2 of the antibody of SEQ ID NO: 1 with CDR(s) of an antibody that recognizes the additional target and/or a polypeptide that binds to the additional target, thereby producing a polypeptide that binds to PD-L1 and the additional target.
3. A method of producing a polypeptide that binds to PD-L1 and an additional target, comprising grafting the CDR3 of the antibody of SEQ ID NO: 1 onto an antibody recognizing the additional target, thereby producing a polypeptide that binds to PD-L1 and the additional target.
4. A method of producing a PD-L1 binding non-immunoglobulin, comprising grafting the CDR3 of the antibody of SEQ ID NO: 1 onto a non-immunoglobulin having a CDR loop-like structure, thereby allowing the non-immunoglobulin to bind to PD-L1.
5. The method of claim 2 , wherein the additional target is selected from tumor antigens and immunological checkpoint-associated antigens.
6. The method of claim 5 , wherein the tumor antigen is selected from VEGFR, ERBB family proteins, and CMET.
7. The method of claim 5 , wherein the immunological checkpoint-associated antigen is CTLA4.
8. The method of claim 3 , wherein the additional target is selected from tumor antigens and immunological checkpoint-associated antigens.
9. The method of claim 8 , wherein the tumor antigen is selected from VEGFR, ERBB family proteins, and CMET.
10. The method of claim 8 , wherein the immunological checkpoint-associated antigen is CTLA4.
11. The method of claim 4 , wherein the non-immunoglobulin having a CDR loop-like structure is a CTLA4 protein, or a fibronectin type III domain.