Anti-LAG-3 antibodies and uses thereof
The present disclosure provides antibodies that bind Lymphocyte Activation Gene-3 (LAG-3). Also provided are methods of stimulating an immune response, inhibiting growth of tumor cells, and treating an autoimmune, inflammatory, or viral disease.
1. An antibody or fragment thereof, wherein the antibody or fragment thereof has specificity to a human Lymphocyte Activation Gene-3 (LAG-3) protein and comprises a heavy chain variable region comprising heavy chain complementarity determining regions CDRH1, CDRH2, and CDRH3, and a light chain variable region comprising light chain complementarity determining regions CDRL1, CDRL2, and CDRL3, and wherein
the CDRH1 comprises the amino acid sequence of SEQ ID NO:240;
the CDRH2 comprises the amino acid sequence of SEQ ID NO:241 or SEQ ID NO:347;
the CDRH3 comprises the amino acid sequence of SEQ ID NO:242 or SEQ ID NO:354;
the CDRL1 comprises the amino acid sequence of SEQ ID NO:243, SEQ ID NO:376 or amino acid residues 24-39 of SEQ ID NO:330;
the CDRL2 comprises the amino acid sequence of SEQ ID NO:244; and
the CDRL3 comprises the amino acid sequence of SEQ ID NO:245 or SEQ ID NO:374.
2. The antibody or fragment thereof of claim 1 , wherein
the CDRH1 comprises the amino acid sequence of SEQ ID NO:240;
the CDRH2 comprises the amino acid sequence of SEQ ID NO:241;
the CDRH3 comprises the amino acid sequence of SEQ ID NO:242;
the CDRL1 comprises the amino acid sequence of SEQ ID NO:243;
the CDRL2 comprises the amino acid sequence of SEQ ID NO:244; and
the CDRL3 comprises the amino acid sequence of SEQ ID NO:245.
3. The antibody or fragment thereof of claim 2 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:238, and the light chain variable region comprises the amino acid sequences of SEQ ID NO:239.
4. The antibody or fragment thereof of claim 2 , wherein the heavy chain variable region comprises an amino acid sequence of selected from the group consisting of SEQ ID NO:251, 252, 258 and 259, and the light chain variable region comprises the amino acid sequences of SEQ ID NO:260.
5. The antibody or fragment thereof of claim 1 , wherein
the CDRH1 comprises the amino acid sequence of SEQ ID NO:240;
the CDRH2 comprises the amino acid sequence of SEQ ID NO:347;
the CDRH3 comprises the amino acid sequence of SEQ ID NO:354;
the CDRL1 comprises the amino acid sequence of amino acid residues 24-39 of SEQ ID NO:330;
the CDRL2 comprises the amino acid sequence of SEQ ID NO:244; and
the CDRL3 comprises the amino acid sequence of SEQ ID NO:374.
6. The antibody or fragment thereof of claim 5 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:329, and the light chain variable region comprises the amino acid sequences of SEQ ID NO:330.
7. The antibody or fragment thereof of claim 1 , wherein
the CDRH1 comprises the amino acid sequence of SEQ ID NO:240;
the CDRH2 comprises the amino acid sequence of SEQ ID NO:347;
the CDRH3 comprises the amino acid sequence of SEQ ID NO:354;
the CDRL1 comprises the amino acid sequence of SEQ ID NO:376;
the CDRL2 comprises the amino acid sequence of SEQ ID NO:244; and
the CDRL3 comprises the amino acid sequence of SEQ ID NO:374.
8. The antibody or fragment thereof of claim 1 , further comprising a heavy chain constant region or a light chain constant region.
9. The antibody or fragment thereof of claim 1 , which is bispecific.
10. The antibody or fragment thereof of claim 9 , wherein the bispecificity comprises a second specificity to an immune checkpoint protein or a tumor antigen.
11. The antibody or fragment thereof of claim 9 , wherein the bispecificity comprises a second specificity to a protein target selected from the group consisting of PD-L1, PD-1, CTLA-4, CD28, CD122, 4-1BB, TIM3, OX-40, OX40L, CD40, CD40L, LIGHT, ICOS, ICOSL, GITR, GITRL, TIGIT, CD27, VISTA, B7H3, B7H4, HEVM, BTLA, KIR, CD47, CD73, EGFR, Her2, CD33, CD133, CEA and VEGF.
12. The antibody or fragment thereof of claim 9 , wherein the bispecificity comprises a second specificity to PD-L1.
13. A composition comprising the antibody or fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
14. One or more polynucleotides encoding the antibody or fragment thereof of claim 1 .