Methods and antibodies for modulation of immunoresponse

Abstract

Provided are an anti-CD11b antibody or an antigen-binding portion thereof, and methods and use of the antibody for modulating immunoresponses by regulating CD11b expression on cells.

What is claimed is: 
     
         1 . An antibody or antigen-binding portion thereof comprising:
 (i) a heavy chain variable region comprising H-CDR1 having the sequence of SEQ ID NO:1, H-CDR2 having the sequence of SEQ ID NO:3, and H-CDR3 having the sequence of SEQ ID NO:5; or a heavy chain variable region comprising H-CDR1 having the sequence of SEQ ID NO:2, H-CDR2 having the sequence of SEQ ID NO:4, and H-CDR3 having the sequence of SEQ ID NO:6; and   (ii) a light chain variable region comprising L-CDR1 having the sequence of SEQ ID NO:7, L-CDR2 having the sequence of SEQ ID NO:9, and L-CDR3 having the sequence of SEQ ID NO: 11; or a light chain variable region comprising L-CDR1 having the sequence of SEQ ID NO:8, L-CDR2 having the sequence of SEQ ID NO:10, and L-CDR3 having the sequence of SEQ ID NO:12.   
     
     
         2 . The antibody or antigen-binding portion thereof according to  claim 1 , the antibody or the antigen-binding portion thereof comprising:
 a heavy chain variable region comprising the amino acid sequence of one of SEQ ID NO: 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22, and   a light chain variable region comprising the amino acid sequence of one of SEQ ID NO: 23, 24, 25, 26, 27, 28, 29, 30, 31, or 32.   
     
     
         3 . The antibody or the antigen-binding portion thereof according to  claim 1 , the antibody or antigen-binding portion thereof comprising,
 (a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 13, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:23;   (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:14, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:24;   (c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 15, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:25;   (d) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:16, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:26;   (e) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:17, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:27;   (f) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 18, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:28;   (g) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 19, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:29;   (h) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:20, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:30;   (i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:21, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:31; or   (j) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:22, and a light chain variable region comprising the amino acid sequence of SEQ ID NO:32.   
     
     
         4 . A composition comprising the antibody or antigen-binding portion thereof according to  claim 1 . 
     
     
         5 . A pharmaceutical composition comprising the antibody or the antigen-binding portion thereof according to  claim 1 . 
     
     
         6 . A pharmaceutical composition comprising the antibody or the antigen-binding portion thereof according to  claim 2 . 
     
     
         7 . A pharmaceutical composition comprising the antibody or the antigen-binding portion thereof according to  claim 3 . 
     
     
         8 . The pharmaceutical composition according to  claim 5 , wherein the pharmaceutical composition further comprises an agent that modulates an immune checkpoint or a chemotherapeutic agent. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , wherein the agent that modulates an immune checkpoint comprises an anti-PD-1 antibody, a PD-1 ligand, an anti-PD-L1 antibody, a PD-L1 ligand, an anti-CTLA-4 antibody, a CTLA-4 ligand, or a binding fragment thereof. 
     
     
         10 . The pharmaceutical composition according to  claim 8 , wherein the chemotherapeutic agent comprises cisplatin, 5-FU, taxol, docetaxel, vinorelbine, vindesine, vinflunine, gemcitabine, methotrexate, gefitinib, lapatinib, or erlotinib. 
     
     
         11 . The pharmaceutical composition according to  claim 6 , wherein the pharmaceutical composition further comprises an agent that modulates an immune checkpoint or a chemotherapeutic agent. 
     
     
         12 . The pharmaceutical composition according to  claim 11 , wherein the agent that modulates an immune checkpoint comprises an anti-PD-1 antibody, a PD-1 ligand, an anti-PD-L1 antibody, a PD-L1 ligand, an anti-CTLA-4 antibody, a CTLA-4 ligand, or a binding fragment thereof. 
     
     
         13 . The pharmaceutical composition according to  claim 11 , wherein the chemotherapeutic agent comprises cisplatin, 5-FU, taxol, docetaxel, vinorelbine, vindesine, vinflunine, gemcitabine, methotrexate, gefitinib, lapatinib or erlotinib. 
     
     
         14 . The pharmaceutical composition according to  claim 7 , wherein the pharmaceutical composition further comprises an agent that modulates an immune checkpoint or a chemotherapeutic agent. 
     
     
         15 . The pharmaceutical composition according to  claim 14 , wherein the agent that modulates an immune checkpoint comprises an anti-PD-1 antibody, a PD-1 ligand, an anti-PD-L1 antibody, a PD-L1 ligand, an anti-CTLA-4 antibody, a CTLA-4 ligand, or a binding fragment thereof. 
     
     
         16 . The pharmaceutical composition according to  claim 14 , wherein the chemotherapeutic agent comprises cisplatin, 5-FU, taxol, docetaxel, vinorelbine, vindesine, vinflunine, gemcitabine, methotrexate, gefitinib, lapatinib or erlotinib.