ANTI-GAL3 ANTIBODIES AND USES THEREOF
Disclosed herein are antibodies that specifically bind to Gal3 and methods of use thereof. In some embodiments, also described herein are methods of inducing immune activation or promoting T cell or Natural Killer cell proliferation with an antibody that specifically binds to Gal3. Also disclosed herein are methods and compositions of reducing fibrosis or propensity thereof in a tissue with antibodies that specifically bind to Gal3. In some cases, the anti-Gal3 antibody also disrupts the interaction between Gal3 and TIM-3.
1 - 5 . (canceled)
6 . A method of inducing immune activation, comprising:
contacting a plurality of cells comprising a Gal3-expressing cell and a TIM-3-expressing cell with an anti-Gal3 antibody or binding fragment thereof under conditions to disrupt an interaction between Gal3 and TIM-3,
wherein upon binding to the antibody or binding fragment thereof, the Gal3-expressing cell expresses a cytokine which induces immune activation,
wherein the anti-Gal3 antibody or binding fragment thereof comprises (1) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3; and (2) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3, wherein
the VH-CDR1 comprises the amino acid sequence according to SEQ ID NO: 62, the VH-CDR2 comprises the amino acid sequence according to SEQ ID NO: 90, the VH-CDR3 comprises the amino acid sequence according to SEQ ID NO: 118, the VL-CDR1 comprises the amino acid sequence according to SEQ ID NO: 146, the VL-CDR2 comprises the amino acid sequence RMS, the VL-CDR3 comprises the amino acid sequence according to SEQ ID NO: 202.
7 . The method of claim 6 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region (VH) having the amino acid sequence according to SEQ ID NO: 230; and a light chain variable region (VL) having the amino acid sequence according to SEQ ID NO: 258.
8 . The method of claim 6 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain having the amino acid sequence according to SEQ ID NO: 265; and a light chain having the amino acid sequence according to SEQ ID NO: 266.
9 . The method of claim 6 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region having at least 90% identity to the amino acid sequence according to SEQ ID NO: 230; and a light chain variable region having at least 90% identity to the amino acid sequence according to SEQ ID NO: 258.
10 . The method of claim 6 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain having at least 90% identity to the amino acid sequence according to SEQ ID NO: 265; and a light chain having at least 90% identity to the amino acid sequence according to SEQ ID NO: 266.
11 . The method of claim 6 , wherein the Gal3-TIM-3 interaction is reduced by up to 70%.
12 . A method of promoting T cell or Natural Killer (NK) cell proliferation, comprising:
contacting a plurality of cells comprising T cells, NK cells, and a Gal3-expressing cell with an anti-Gal3 antibody or binding fragment thereof under conditions to effect proliferation of T cells and/or NK cells in the plurality of cells,
wherein the anti-Gal3 antibody or binding fragment thereof comprises (1) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3; and (2) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3, wherein
the VH-CDR1 comprises the amino acid sequence according to SEQ ID NO: 62, the VH-CDR2 comprises an amino acid sequence according to SEQ ID NO: 90, the VH-CDR3 comprises an amino acid sequence according to SEQ ID NO: 118, the VL-CDR1 comprises an amino acid sequence according to SEQ ID NO: 146, the VL-CDR2 comprises the amino acid sequence RMS, the VL-CDR3 comprises an amino acid sequence according to SEQ ID NO: 202.
13 . The method of claim 12 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region (VH) having the amino acid sequence according to SEQ ID NO: 230; and a light chain variable region (VL) having the amino acid sequence according to SEQ ID NO: 258.
14 . The method of claim 12 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain having the amino acid sequence according to SEQ ID NO: 265; and a light chain having the amino acid sequence according to SEQ ID NO: 266.
15 . The method of claim 12 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region having at least 90% identity to the amino acid sequence according to SEQ ID NO: 230; and a light chain variable region having at least 90% identity to the amino acid sequence according to SEQ ID NO: 258.
16 . The method of claim 12 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain having at least 90% identity to the amino acid sequence according to SEQ ID NO: 265; and a light chain having at least 90% identity to the amino acid sequence according to SEQ ID NO: 266.
17 . The method of claim 12 , wherein the Gal3-TIM-3 interaction is reduced by up to 70%.
18 . A method of treating cancer, comprising:
contacting a plurality of cells comprising a Gal3-expressing cell and a TIM-3-expressing cell with an anti-Gal3 antibody or binding fragment thereof under conditions to disrupt an interaction between Gal3 and TIM-3,
wherein the anti-Gal3 antibody or binding fragment thereof comprises (1) a light chain variable region comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3; and (2) a heavy chain variable region comprising a VH-CDR1, a VH-CDR2, and a VH-CDR3, wherein
the VH-CDR1 comprises an amino acid sequence according to SEQ ID NO: 62, the VH-CDR2 comprises an amino acid sequence according to SEQ ID NO: 90, the VH-CDR3 comprises an amino acid sequence according to SEQ ID NO: 118, the VL-CDR1 comprises an amino acid sequence according to SEQ ID NO: 146, the VL-CDR2 comprises the amino acid sequence RMS, the VL-CDR3 comprises an amino acid sequence according to SEQ ID NO: 202.
19 . The method of claim 18 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region (VH) having the amino acid sequence according to SEQ ID NO: 230; and a light chain variable region (VL) having the amino acid sequence according to SEQ ID NO: 258.
20 . The method of claim 18 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain having the amino acid sequence according to SEQ ID NO: 265; and a light chain having the amino acid sequence according to SEQ ID NO: 266.
21 . The method of claim 18 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain variable region having at least 90% identity to the sequence according to SEQ ID NO: 230; and a light chain variable region having at least 90% identity to the sequence according to SEQ ID NO: 258.
22 . The method of claim 18 , wherein the anti-Gal3 antibody or binding fragment thereof comprises a heavy chain having at least 90% identity to the amino acid sequence according to SEQ ID NO: 265; and a light chain having at least 90% identity to the amino acid sequence according to SEQ ID NO: 266.
23 . The method of claim 18 , wherein the cancer is a metastatic cancer, a relapsed cancer, or a refractory cancer.
24 . The method of claim 18 , wherein the cancer is breast cancer, colorectal cancer, kidney cancer, liver cancer, lung cancer, or a hematological malignancy.
25 . The method of claim 18 , wherein the Gal3-TIM-3 interaction is reduced by up to 70%.