Binder against programmed death-ligand and application thereof
Provided is an anti-PD-L1 monoclonal antibody. The antibody can be used to prepare a drug for preventing or treating a disease related to PD-L1.
1. An antibody specific against PD-L1, wherein the antibody comprises:
(1) a heavy chain variable region comprising the following three complementary determining regions (CDRs):
CDR1 as shown in SEQ ID NO: 3,
CDR2 as shown in SEQ ID NO: 4, and
CDR3 as shown in SEQ ID NO: 5; and
(2) a light chain variable region comprising the following three complementarity determining regions (CDRs):
CDR1′ as shown in SEQ ID NO: 6,
CDR2′, wherein the amino acid sequence of CDR2′ is GIS, and
CDR3′ as shown in SEQ ID NO: 7.
2. The antibody of claim 1 , wherein the antibody is selected from the group consisting of a murine antibody, a chimeric antibody, and a humanized antibody.
3. The antibody of claim 1 , wherein the heavy chain variable region sequence of the antibody is as shown in SEQ ID NO: 1, and the light chain variable region sequence of the antibody is as shown in SEQ ID NO: 2 or
wherein the heavy chain variable region sequence of the antibody is as shown in SEQ ID NO: 8, and the light chain variable region sequence of the antibody is as shown in SEQ ID NO: 9.
4. A recombinant protein which comprises:
(i) the antibody of claim 1 ; and
(ii) an optional tag sequence that assists expression and/or purification.
5. A CAR construct, wherein the antigen binding domain of the CAR construct comprises a scFv that specifically binds to PD-L1, and the scFv has a heavy chain variable region comprising the following three complementary determining regions (CDRs):
CDR1 as shown in SEQ ID NO: 3,
CDR2 as shown in SEQ ID NO: 4, and
CDR3 as shown in SEQ ID NO: 5; and
a light chain variable region comprising the following three complementarity determining regions (CDRs):
CDR1′ as shown in SEQ ID NO: 6,
CDR2′, wherein the amino acid sequence of CDR2′ is GIS, and
CDR3′ as shown in SEQ ID NO: 7.
6. The antibody of claim 1 , wherein the heavy chain variable region sequence of the antibody is as shown in SEQ ID NO: 1; and
the light chain variable region sequence of the antibody is as shown in SEQ ID NO: 2.
7. The antibody of claim 1 , wherein the heavy chain variable region sequence of the antibody is as shown in SEQ ID NO: 8; and
the light chain variable region sequence of the antibody is as shown in SEQ ID NO: 9.
8. A method for treating PD-L1-related diseases, wherein the method comprises: administering the antibody of claim 1 to a subject in need, wherein the PD-L1-related diseases comprise tumors with positive PD-L1 expression.
9. A method for in vitro detection of PD-L1 protein in a sample, wherein the method comprises the steps:
(1) contacting the sample with the antibody of claim 1 in vitro;
(2) detecting whether an antigen-antibody complex is formed, wherein the formation of the complex indicates the presence of PD-L1 protein in the sample.
10. A pharmaceutical composition comprising:
(i) an active ingredient, which is the antibody of claim 1 ; and
(ii) a pharmaceutically acceptable carrier.