Antibodies binding LAG-3 and uses thereof
The present invention provides an isolated monoclonal antibody that specifically binds LAG-3. A nucleic acid molecule encoding the antibody, an expression vector, a host cell and a method for expressing the antibody are also provided. The present invention further provides an immunoconjugate, a bispecific molecule and a pharmaceutical composition comprising the antibody, as well as a diagnostic and treatment method using an anti-LAG-3 antibody of the invention.
1. An isolated monoclonal antibody, or an antigen-binding portion thereof, that binds LAG-3, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises a CDR1 region comprising the amino acid sequence of SEQ ID NO:2, a CDR2 region comprising the amino acid sequence of SEQ ID NO:4, and a CDR3 region comprising the amino acid sequence of SEQ ID NO:6, wherein the light chain variable region comprises a CDR1 region comprising the amino acid sequence of SEQ ID NO:8, a CDR2 region comprising the amino acid sequence of SEQ ID NO: 10, and a CDR3 region comprising the amino acid sequence of SEQ ID NO: 12.
2. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 32.
3. The isolated monoclonal antibody, or the antigen-binding portion thereof, of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO:34.
4. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:36, and a light chain comprising the amino acid sequence of SEQ ID NO:38.
5. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , comprising the amino acid sequence of SEQ ID NO:30.
6. The isolated monoclonal antibody, or the antigen-binding portion thereof, of claim 1 , which exhibits one or a combination of the following properties: (a) binding to human LAG-3; (b) binding to monkey LAG-3; (c) lack of binding to mouse LAG-3; (d) binding to LAG-3 at a domain histocompatibility (MHC) class II bind to; (e) inhibits binding of LAG-3 to major histocompatibility (MHC) class II molecules; (f) inhibits binding of LAG-3 to LSECtin; (g) stimulates an immune response; and (h) stimulates an antigen-specific T cell response.
7. The isolated monoclonal antibody, or the antigen-binding portion thereof, of claim 1 , which is an IgG1, IgG2 or IgG4 isotype.
8. The isolated monoclonal antibody, or the antigen-binding portion thereof, of claim 1 , which is a human, humanized, or chimeric antibody.
9. A composition comprising the isolated monoclonal antibody, or the antigen-binding portion thereof, of claim 1 , and a pharmaceutically acceptable carrier.
10. The composition of claim 9 , further comprising an anti-cancer agent or an anti-viral agent.
11. A method of treating tumor or viral infection in a subject comprising administering to the subject the isolated monoclonal antibody, or antigen-binding portion thereof, of claim 1 .
12. The method of claim 11 , wherein at least one additional immunostimulatory antibody is further administered to the subject.
13. The method of claim 12 , wherein the immunostimulatory antibody is an anti-PD-1 antibody, an anti-PD-L1 antibody or an anti-CTLA-4 antibody.
14. The method of claim 11 , wherein, a cytokine is further administered to the subject.
15. The method of claim 14 , wherein, the cytokine is IL-2 or IL-21.
16. The method of claim 11 , wherein, a costimulatory antibody is further administered to the subject.
17. The method of claim 16 , wherein, the costimulatory antibody is an anti-CD137 or an anti-GITR antibody.
18. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:32, and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 34.
19. The method of claim 11 , wherein the subject is human.