Antibodies against LIF and uses thereof
Described herein are antibodies that target Leukemia Inhibitory Factor (LIF). Also described herein are uses of these antibodies for the treatment of cancer.
1. A recombinant antibody that specifically binds Leukemia Inhibitory Factor (LIF), the antibody comprising:
a) a heavy chain complementarity determining region 1 (VH-CDR1) comprising the amino acid sequence set forth in SEQ ID NO: 2 (GFTFSHAW);
b) a heavy chain complementarity determining region 2 (VH-CDR2) comprising the amino acid sequence set forth in SEQ ID NO: 10 (IKAKSDDYAT);
c) a heavy chain complementarity determining region 3 (VH-CDR3) comprising the amino acid sequence set forth in SEQ ID NO: 15 (TCWEWDLDF);
d) a light chain complementarity determining region 1 (VL-CDR1) comprising the amino acid sequence set forth in SEQ ID NO: 22 (QSLLDSDGHTY);
e) a light chain complementarity determining region 2 (VL-CDR2) comprising the amino acid sequence set forth in SEQ ID NO: 26 (SVS); and
f) a light chain complementarity determining region 3 (VL-CDR3) comprising the amino acid sequence set forth in SEQ ID NO: 29 (MQATHAPPYT).
2. The recombinant antibody of claim 1 , wherein the recombinant antibody binds to glycosylated LIF.
3. The recombinant antibody of claim 1 , wherein the recombinant antibody is humanized.
4. The recombinant antibody of claim 1 , wherein the recombinant antibody is deimmunized.
5. The recombinant antibody of claim 1 , wherein the recombinant antibody comprises two heavy chains and two light chains.
6. The recombinant antibody of claim 1 , wherein the recombinant antibody is an IgG antibody.
7. The recombinant antibody of claim 1 , wherein the recombinant antibody is a Fab, F(ab) 2 , single-domain antibody, a single chain variable fragment (scFv), or a nanobody.
8. The recombinant antibody of claim 1 , wherein the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 1 (GFTFSHAWMH), the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 9 (QIKAKSDDYATYYAESVKG), and the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 15 (TCWEWDLDF), and wherein the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 21 (RSSQSLLDSDGHTYLN), the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 25 (SVSNLES), and the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 29 (MQATHAPPYT).
9. The recombinant antibody of claim 1 , wherein the heavy chain comprises a VH sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 72; and the light chain comprises a VL sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 76.
10. The recombinant antibody of claim 9 , wherein the VH sequence is at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 72; and the VL sequence is at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 76.
11. The recombinant antibody of claim 9 , wherein the VH sequence comprises the amino acid sequence set forth in SEQ ID NO: 72, and the VL sequence comprises the amino acid sequence set forth in SEQ ID NO: 76.
12. The recombinant antibody of claim 1 , wherein the heavy chain comprises a sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 88; and the light chain comprises a sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 92.
13. The recombinant antibody of claim 12 , wherein the heavy chain comprises the sequence at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 88; and the light chain comprises the sequence at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 92.
14. The recombinant antibody of claim 13 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 88; and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 92.
15. A pharmaceutical composition comprising the recombinant antibody of claim 1 and a pharmaceutically acceptable carrier.
16. The pharmaceutical composition of claim 15 , formulated for intravenous injection.
17. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is in lyophilized form.