Anti-HLA-G antibodies, compositions comprising anti-HLA-G antibodies and methods of using anti-HLA-G antibodies
Provided herein are antibodies that selectively bind to HLA-G and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.
1. An antibody that specifically binds to human HLA-G (hHLA-G), comprising a heavy chain variable region (V H ) and a light chain variable region (VL), wherein
a) the V H comprises:
i) a V H -complementarity determining region (CDR) 1 comprising the amino acid sequence set forth in SEQ ID NO: 7; a VHCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 44; and a VHCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 93, wherein the CDRs are according to Chothia; or
ii) a VHCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 25; a VHCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 65; and a VHCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 93, wherein the CDRs are according to Kabat; and
b) the VL comprises:
i) a VLCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 118; a VLCDR2 comprising the amino acid sequence set forth in SEQ ID NO: 138; and a VLCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 155, wherein the CDRs are according to Chothia and Kabat.
2. The antibody of claim 1 , comprising a V H sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 192 and a VL sequence that is at least 85% identical to the amino acid sequence set forth in SEQ ID NO: 220.
3. The antibody of claim 1 , comprising a V H sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 192 and a VL sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 220.
4. The antibody of claim 1 , wherein the antibody comprises a heavy chain of SEQ ID NO: 254 and a light chain of SEQ ID NO: 322.
5. The antibody of claim 1 , wherein the antibody comprises a heavy chain of SEQ ID NO: 288 and a light chain of SEQ ID NO: 322.
6. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
7. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or excipient.
8. The pharmaceutical composition of claim 7 , further comprising an effective amount of at least one of the following:
a) an anti-ILT2 antibody;
b) an anti-ILT4 antibody;
c) an anti-KIR2DL4 antibody;
d) an anti-HLA-E antibody;
e) an anti-NKG2A antibody
f) an anti-HLA-F antibody
g) an anti-PD-L1 antibody;
h) an anti-PD-1 antibody;
i) an anti-CD38 antibody;
j) an anti-CD39 antibody;
k) an anti-CD73 antibody;
l) an anti-A2A receptor antibody;
m) an anti-A2B receptor antibody;
n) an anti-A2A/A2B dual receptor antibody or a combination thereof;
o) an anti-CD47 antibody;
p) an anti-CTLA-4 antibody;
q) an anti-TIM-3 antibody;
r) an anti-TIGIT antibody;
s) an anti-VISTA antibody;
t) an anti-CD94 antibody;
u) a small molecule inhibitor;
v) an oncolytic virus;
w) a chemotherapy; and/or
x) ADCC capable therapies using effector competent antibodies selected from the group consisting of anti-CD19, anti-CD20, anti-EGFR, anti-Her2, anti-SLAMF7, anti-CD52, anti-BCMA, anti-GD2, and anti-CCR4.
9. The pharmaceutical composition of claim 8 , further comprising one or both of
a) an antibody to an immune inhibitory receptor or ligand and/or
b) an antibody to an immune stimulatory receptor or ligand.
10. A kit comprising the antibody of claim 1 .