Antibodies against TIM3 and uses thereof
Provided herein are antibodies, or antigen-binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen-binding portions thereof, polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof.
1. A nucleic acid or a set of nucleic acids comprising nucleotide sequences encoding a heavy chain variable region (VH), a light chain variable region (VL), or both a heavy and a light chain variable region of an antibody that specifically binds to human TIM3; wherein the VH comprises a heavy chain CDR1, CDR2, and CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 41, 122, and 126, respectively; and wherein the VL comprises a light chain CDR1, CDR2, and CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 64, 66, and 68, respectively.
2. The nucleic acid or the set of nucleic acids of claim 1 , wherein the VH comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 364, and wherein the VL comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 60.
3. The nucleic acid or the set of nucleic acids of claim 1 , wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 364, and wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 60.
4. The nucleic acid or the set of nucleic acids of claim 1 , wherein
(a) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 349 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(b) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 351 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(c) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 353 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(d) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 350 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29;
(e) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 352 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29; or
(f) the heavy chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 354 and the light chain comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29.
5. The nucleic acid or the set of nucleic acids of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 349 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
6. The nucleic acid or the set of nucleic acids of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 351 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
7. The nucleic acid or the set of nucleic acids of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 353 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
8. The nucleic acid or the set of nucleic acids of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 350 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
9. The nucleic acid or the set of nucleic acids of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 352 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
10. The nucleic acid or the set of nucleic acids of claim 1 , wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 354 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29.
11. The nucleic acid or the set of nucleic acids of claim 1 , wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, and a variant thereof.
12. The nucleic acid or the set of nucleic acids of claim 1 , wherein the antibody comprises an effectorless IgG1 Fe.
13. The nucleic acid or the set of nucleic acids of claim 1 , comprising a first nucleotide sequence encoding the VH and a second nucleotide sequence encoding the VL.
14. The nucleic acid or the set of nucleic acids of claim 1 , comprising a first nucleotide sequence encoding the VH, and a second nucleotide sequence encoding the VL, a third nucleotide sequence encoding a second VH, and a fourth nucleotide sequence encoding a second VL.
15. The nucleic acid or the set of nucleic acids of claim 14 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 351, and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
16. The nucleic acid or the set of nucleic acids of claim 1 , comprising a nucleotide sequence having at least 75% sequence identity to the nucleotide sequence set forth in SEQ ID NO: 355, and a nucleotide sequence having at least 75% sequence identity to the nucleotide sequence set forth in SEQ ID NO: 162.
17. The nucleic acid or the set of nucleic acids of claim 1 , comprising the nucleotide sequence set forth in SEQ ID NO: 355 and the nucleotide sequence set forth in SEQ ID NO: 162.
18. The nucleic acid or the set of nucleic acids of claim 1 , comprising a nucleotide sequence having at least 75% sequence identity to the nucleotide sequence set forth in SEQ ID NO: 356, and a nucleotide sequence having at least 75% sequence identity to the nucleotide sequence set forth in SEQ ID NO: 162.
19. The nucleic acid or the set of nucleic acids of claim 1 , comprising the nucleotide sequence set forth in SEQ ID NO: 356 and the nucleotide sequence set forth in SEQ ID NO: 162.