TREATING CANCER BY BLOCKING THE INTERACTION OF TIM-3 AND ITS LIGAND
Provided herein are methods of activating immune response and/or treating cancer in a patient comprising administering to the patient a Gal3:TIM-3 inhibitor that interferes with the interaction between Gal3 and TIM-3, where said inhibitor is administered in an amount sufficient to activate immune response. Also provided are a humanized anti-Gal3 antibodies that can block the interaction between Gal3 and TIM3 and methods of using the anti-Gal3 antibody to treat cancer. Methods for determining if a patient's cancer is suitable for treatment with a Gal3:TIM-3 inhibitor and methods for selecting compounds that can block interaction between Gal3 and TIM-3, activating immune response and/or treating cancer are also provided.
1 . An anti-Gal3 antibody or a binding fragment thereof, wherein the antibody comprises:
(1) a light chain variable region comprising a complementary determining region (CDR) L1, a CDR L2, and a CDR L3 and
(2) a heavy chain variable region comprising a CDR H1, a CDR H2, and a CDR H3, wherein
the CDR L1 comprises the amino acid sequence of SEQ ID NO:17,
the CDR L2 comprises the amino acid sequence of SEQ ID NO:18,
the CDR L3 comprises the amino acid sequence of SEQ ID NO:19,
the CDR H1 comprises the amino acid sequence of SEQ ID NO:9,
the CDR H2 comprises the amino acid sequence of SEQ ID NO:10, and
the CDR H3 comprises the amino acid sequence of SEQ ID NO:11.
2 . The anti-GAL3 antibody of claim 1 , comprising:
a heavy chain variable region (VH) sequence having at least about 90% identity to SEQ ID NO: 25.
3 . The anti-GAL3 antibody of claim 1 , comprising:
a light chain variable region (VL) having at least about 90% identity to SEQ ID NO: 26.
4 . The anti-GAL3 antibody of claim 1 , comprising:
a heavy chain variable region (VH) sequence having at least about 90% identity to SEQ ID NO: 25; and
a light chain variable region (VL) having at least about 90% identity to SEQ ID NO: 26.
5 . The anti-GAL3 antibody of claim 1 , comprising:
a heavy chain variable region (VH) comprising SEQ ID NO: 25.
6. The anti-GAL3 antibody of claim 1 , comprising:
a light chain variable region (VL) comprising SEQ ID NO: 26.
7 . The anti-GAL3 antibody of claim 1 , comprising:
a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 25; and
a light chain variable region (VL) comprising the sequence of SEQ ID NO: 26.
8 . The anti-GAL3 antibody of claim 1 , comprising:
a heavy chain comprising a sequence having at least about 90% identity to SEQ ID NO: 16.
9 . The anti-GAL3 antibody of claim 1 , comprising:
a light chain comprising a sequence having at least about 90% identity to SEQ ID NO: 24.
10 . The anti-GAL3 antibody of claim 1 , comprising:
a heavy chain comprising a sequence having at least about 90% identity to SEQ ID NO: 16; and
a light chain comprising a sequence having at least about 90% identity to SEQ ID NO: 24.
11 . The anti-GAL3 antibody of claim 1 , comprising:
a heavy chain comprising the sequence of SEQ ID NO: 16.
12 . The anti-GAL3 antibody of claim 1 , comprising:
a light chain comprising the sequence of SEQ ID NO: 24.
13 . The anti-GAL3 antibody of claim 1 , comprising:
a heavy chain comprising the sequence of SEQ ID NO: 16; and
a light chain comprising the sequence of SEQ ID NO: 24.
14 . An anti-Gal3 antibody or a binding fragment thereof, wherein the antibody comprises:
(1) a light chain variable region comprising a complementary determining region (CDR) L1, a CDR L2, and a CDR L3 and
(2) a heavy chain variable region comprising a CDR H1, a CDR H2, and a CDR H3, wherein
the CDR L1 comprises an amino acid sequence having at least about 90% identity to SEQ ID NO:17,
the CDR L2 comprises an amino acid sequence having at least about 90% identity to SEQ ID NO:18,
the CDR L3 comprises an amino acid sequence having at least about 90% identity to SEQ ID NO:19,
the CDR H1 comprises an amino acid sequence having at least about 90% identity to SEQ ID NO:9,
the CDR H2 comprises an amino acid sequence having at least about 90% identity to SEQ ID NO:10, and
the CDR H3 comprises an amino acid sequence having at least about 90% identity to SEQ ID NO:11.
15 . The anti-GAL3 antibody of claim 14 , comprising:
a heavy chain variable region (VH) comprising a sequence having at least about 90% identity to SEQ ID NO: 25.
16 . The anti-GAL3 antibody of claim 14 , comprising:
a light chain variable region (VL) comprising a sequence having at least about 90% identity to SEQ ID NO: 26.
17 . The anti-GAL3 antibody of claim 14 , comprising:
a heavy chain variable region (VH) comprising a sequence having at least about 90% identity to SEQ ID NO: 25; and
a light chain variable region (VL) comprising a sequence having at least about 90% identity to SEQ ID NO: 26.
18 . The anti-GAL3 antibody of claim 14 , comprising:
a light chain comprising a sequence having at least about 90% identity to SEQ ID NO: 24.
19 . The anti-GAL3 antibody of claim 14 , comprising:
a heavy chain comprising a sequence having at least about 90% identity to SEQ ID NO: 16.
20 . An anti-GAL3 antibody comprising:
a heavy chain variable region comprising a sequence having at least about 90% identity to SEQ ID NO: 16; and
a light chain variable region comprising a sequence having at least about 90% identity to SEQ ID NO: 24.