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 method of treating an individual with cancer comprising administering to the individual a recombinant antibody that specifically binds Leukemia Inhibitory Factor (LIF) 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 SEQ ID NO: 29;
wherein the recombinant antibody specifically binds to LIF, thereby treating the individual with cancer.
2. The method of claim 1 , wherein the recombinant antibody binds to glycosylated LIF.
3. The method of claim 1 , wherein the recombinant antibody comprises at least one framework region derived from a human antibody framework region.
4. The method of claim 1 , wherein the recombinant antibody is humanized.
5. The method of claim 1 , wherein the recombinant antibody is deimmunized.
6. The method of claim 1 , wherein the recombinant antibody comprises two immunoglobulin heavy chains and two immunoglobulin light chains.
7. The method 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 method of claim 1 , wherein the recombinant antibody specifically binds LIF with a dissociation constant (K D ) of less than about 200 picomolar.
9. The method of claim 1 , wherein the recombinant antibody specifically binds LIF with a dissociation constant (K D ) of less than about 100 picomolar.
10. The method 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).
11. The method 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 (QSLLDSDGHTYLN), 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).
12. The method 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).
13. The method of claim 1 , wherein the cancer comprises glioblastoma, a pancreatic cancer, ovarian cancer, colon cancer, prostate cancer, or lung cancer.
14. The method of claim 1 , wherein the recombinant antibody is administered intravenously.
15. The method of claim 1 , wherein the recombinant antibody is administered intracerebrally.
16. A method of treating an individual with cancer comprising administering to the individual a recombinant antibody that specifically binds Leukemia Inhibitory Factor (LIF) comprising:
a) an immunoglobulin heavy chain variable region (VH) sequence with the amino acid sequence identical to the amino acid sequence set forth in SEQ ID NO: 72; and
b) an immunoglobulin light chain variable region (VL) sequence with the amino acid sequence identical to the amino acid sequence set forth in SEQ ID NO: 76, thereby treating the individual with cancer.