Single domain antibody and derivative proteins thereof against programmed death-ligand (PDL1)

1. A programmed death ligand 1 (PDL1) antibody, which specifically binds to PDL1 and comprises at least one immunoglobulin single variable domain, said immunoglobulin single variable domain comprises CDR1, CDR2 and CDR3 selected from the group consisting of:

(1) CDR1 set forth in SEQ ID NO:1, CDR2 set forth in SEQ ID NO:2, CDR3 set forth in SEQ ID NO:3;

(2) CDR1 set forth in SEQ ID NO:4, CDR2 set forth in SEQ ID NO:5, CDR3 set forth in SEQ ID NO:6;

(3) CDR1 set forth in SEQ ID NO:7, CDR2 set forth in SEQ ID NO:8, CDR3 set forth in SEQ ID NO:9;

(4) CDR1 set forth in SEQ ID NO:10, CDR2 set forth in SEQ ID NO:11, CDR3 set forth in SEQ ID NO:12;

(5) CDR1 set forth in SEQ ID NO:13, CDR2 set forth in SEQ ID NO:14, CDR3 set forth in SEQ ID NO:15;

(6) CDR1 set forth in SEQ ID NO:16, CDR2 set forth in SEQ ID NO:17, CDR3 set forth in SEQ ID NO:18;

(7) CDR1 set forth in SEQ ID NO:19, CDR2 set forth in SEQ ID NO:20, CDR3 set forth in SEQ ID NO:21; and

(8) CDR1 set forth in SEQ ID NO:22, CDR2 set forth in SEQ ID NO:23, CDR3 set forth in SEQ ID NO:24,

wherein said immunoglobulin single variable domain is a VHH.

2. The PDL1 antibody of claim 1 , wherein said VHH comprises an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOs:25-32, wherein there is no variation in CDRs of (1)-(8).

3. The PDL1 antibody of claim 1 , wherein said VHH is humanized and comprises an amino acid sequence of any one of SEQ ID NOs:33-37.

4. The PDL1 antibody of claim 1 , which has at least one of the following features:

(a) binding to human PD-PDL1 with a KD of between 1×10 −7 M and 1×10 −11 M;

(b) blocking the interaction between PDL1 and PD-1; and

(c) enhancing activation of PBMCs and/or T cells.

5. The PDL1 antibody of claim 1 , wherein said VHH comprises an amino acid sequence of any one of SEQ ID NOs:25-32.

6. The PDL1 antibody of claim 1 , which further comprises an immunoglobulin Fc region.

7. The PDL1 antibody of claim 6 , wherein the immunoglobulin Fc region is an Fc region of human immunoglobulin.

8. The PDL1 antibody of claim 7 , wherein the amino acid sequence of the immunoglobulin Fc region is selected from SEQ ID NOs:38, 70 and 71.

9. The PDL1 antibody of claim 8 , which comprises an amino acid sequence selected from SEQ ID NOs:39-51 and 72-83.

10. An immunoconjugate, which comprises the PDL1 antibody of claim 1 that is conjugated with a therapeutic moiety.

11. The immunoconjugate of claim 10 , wherein said therapeutic moiety comprises a cytotoxin, a biologically active protein or a radioactive isotope.

12. A pharmaceutical composition comprising the PDL1 antibody of claim 1 , and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising the immunoconjugate of claim 10 , and a pharmaceutically acceptable carrier.

14. A PDL1 antibody, which is obtained by affinity maturation of the PDL1 antibody of claim 1 .

15. A nucleic acid molecule encoding the PDL1 antibody of claim 1 .

16. An expression vector, which comprises the nucleic acid molecule of claim 15 operably linked to an expression regulation element.

17. A host cell which comprises the nucleic acid molecule of claim 15 and is capable of expressing said PDL1 antibody.

18. A host cell which is transformed with the expression vector of claim 16 and is capable of expressing said PDL1 antibody.

19. A method for producing a PDL1 antibody, which comprises:

a) culturing the host cell of claim 17 under conditions that allow expression of the PDL1 antibody;

b) recovering the PDL 1 antibody expressed by the host cell from the culture of step a); and

c) optionally further purifying and/or modifying the PDL1 antibody obtained from step b).

20. A method for detecting the presence of PDL1 and/or the expression level of PDL1 in a biological sample, comprising:

a) contacting the PDL1 antibody of claim 1 with the biological sample and a control sample under conditions allowing formation of a complex between the PDL1 antibody of claim 1 and PDL1.

b) detecting the formation of the complex,

wherein the difference of the complex formation between the biological sample and the control sample indicates the presence of PDL1 and/or the expression level of PDL1 in the sample.