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 nucleic acid encoding a recombinant antibody comprising:
a) a heavy chain complementarity determining region 1 (VH-CDR1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 1-3;
b) a heavy chain complementarity determining region 2 (VH-CDR2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 9-10;
c) a heavy chain complementarity determining region 3 (VH-CDR3) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 15-16;
d) a light chain complementarity determining region 1 (VL-CDR1) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 21-22;
e) a light chain complementarity determining region 2 (VL-CDR2) comprising the amino acid sequence set forth in any one of SEQ ID NOs: 25-26; and
f) a light chain complementarity determining region 3 (VL-CDR3) comprising the amino acid sequence set forth in any one of SEQ ID NO: 29,
wherein the recombinant antibody specifically binds to Leukemia Inhibitory Factor (LIF).
2. The nucleic acid of claim 1 , wherein the recombinant antibody binds to glycosylated LIF.
3. The nucleic acid of claim 1 , wherein the recombinant antibody comprises at least one framework region derived from a human antibody framework region.
4. The nucleic acid of claim 1 , wherein the recombinant antibody is humanized.
5. The nucleic acid of claim 1 , wherein the recombinant antibody is deimmunized.
6. The nucleic acid of claim 1 , wherein the recombinant antibody comprises two immunoglobulin heavy chains and two immunoglobulin light chains.
7. The nucleic acid of claim 1 , wherein the recombinant antibody comprises a Fab, F(ab) 2 , single-domain antibody, a single chain variable fragment (scFv), or a nanobody.
8. The nucleic acid of claim 1 , wherein the recombinant antibody specifically binds LIF with a dissociation constant (K D ) of less than about 200 picomolar.
9. The nucleic acid of claim 1 , wherein the recombinant antibody specifically binds LIF with a dissociation constant (K D ) of less than about 100 picomolar.
10. The nucleic acid of claim 1 , wherein the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 2 (GFTFSHAW), wherein the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 10 (IKAKSDDYAT) wherein the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 15 (TCWEWDLDF), wherein the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 22 (QSLLDSDGHTY), wherein the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 26 (SVS), and wherein the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 29 (MQATHAPPYT).
11. The nucleic acid of claim 1 , wherein the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 3 (HAWMH), wherein the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 9 (QIKAKSDDYATYYAESVKG), wherein the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 16 (WEWDLDF), wherein the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 21 (RSSQSLLDSDGHTYLN), wherein the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 25 (SVSNLES), and wherein the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 29 (MQATHAPPYT).
12. The nucleic acid of claim 1 , wherein the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 1 (GFTFSHAWMH), wherein the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 9 (QIKAKSDDYATYYAESVKG), wherein the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 15 (TCWEWDLDF), wherein the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 21 (RSSQSLLDSDGHTYLN), wherein the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 25 (SVSNLES), and wherein the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 29 (MQATHAPPYT).
13. The nucleic acid of claim 1 , wherein the VH sequence is at least about 90% identical to the amino acid sequence set forth in SEQ ID NO: 72; and the VL sequence is at least about 90% identical to the amino acid sequence set forth in SEQ ID NO: 76.
14. The nucleic acid of claim 13 , wherein the VH sequence is identical to the amino acid sequence set forth in SEQ ID NO: 72; and the VL sequence is identical to the amino acid sequence set forth in SEQ ID NO: 76.
15. The nucleic acid of claim 1 wherein the recombinant antibody comprises:
a) a light chain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 92; and
b) a heavy chain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 88,
wherein the recombinant antibody specifically binds to LIF.
16. The nucleic acid of claim 15 , wherein:
the light chain has the amino acid sequence set forth in SEQ ID NO: 92; and
the heavy chain has the amino acid sequence set forth in SEQ ID NO: 88.