LIVER X RECEPTOR AGONISTS AND USES THEREOF
Disclosed herein are antibody drug conjugates having an antibody or antibody fragment that binds a cell surface molecule on a target cell, wherein the target cell is a lymphocyte and a therapeutic agent that has a therapeutic effect in a subject in need thereof. Further disclosed herein are antibody drug conjugates having an antibody or antibody fragment that binds a cell surface molecule on a target cell; and a therapeutic agent that binds an intracellular moiety of the target cell. These antibody drug conjugates may be used for treating cardiovascular diseases.
1 . An antibody drug conjugate comprising:
a. a liver X receptor agonist, and
b. an antibody that binds a cell surface molecule that is not expressed on a hepatocyte.
2 . The antibody drug conjugate of claim 1 , wherein the cell surface molecule is expressed on a macrophage.
3 . The antibody drug conjugate of claim 1 , wherein the cell surface molecule is CD11a.
4 . The antibody drug conjugate of claim 3 , wherein the antibody has a heavy chain variable domain having at least about 80% sequence identity to SEQ ID NO. 12.
5 . The antibody drug conjugate of claim 1 , wherein the antibody is chemically linked to (a) the liver X receptor agonist or (b) a moiety chemically attached to the liver X receptor agonist.
6 . The antibody drug conjugate of claim 5 , wherein the antibody comprises an unnatural amino acid chemically linked to (a) the liver X receptor agonist or (b) the moiety chemically attached to the liver X receptor agonist.
7 . The antibody drug conjugate of claim 1 , wherein the antibody drug conjugate has the structure I:
8 . An antibody drug conjugate comprising:
a) a liver X receptor agonist, and
b) an antibody that binds to an integrin expressed on a surface of a leukocyte.
9 . The antibody drug conjugate of claim 8 , wherein the antibody has a heavy chain variable domain having at least about 80% sequence identity to SEQ ID NO. 12.
10 . The antibody drug conjugate of claim 8 , wherein the antibody is chemically linked to (a) the liver X receptor agonist or (b) a moiety chemically attached to the liver X receptor agonist.
11 . The antibody drug conjugate of claim 10 , wherein the antibody comprises an unnatural amino acid chemically linked to (a) the liver X receptor agonist or (b) the moiety chemically attached to the liver X receptor agonist.
12 . A method for activating a liver X receptor in a leukocyte, the method comprising contacting the leukocyte with an antibody drug conjugate comprising:
a) a liver X receptor agonist, and
b) an antibody specific for a cell surface molecule of the leukocyte, wherein the cell surface molecule is not present on a hepatocyte.
13 . The method of claim 12 , wherein the cell surface molecule is an integrin.
14 . The method of claim 12 , wherein the antibody has a heavy chain variable domain having at least about 80% sequence identity to SEQ ID NO. 12.
15 . The method of claim 12 , wherein the liver X receptor comprises liver X receptor alpha, liver X receptor beta, or a combination thereof.
16 . The method of claim 12 , wherein the antibody is chemically linked to (a) the liver X receptor agonist or (b) a moiety chemically attached to the liver X receptor agonist.
17 . The method of claim 16 , wherein the antibody comprises an unnatural amino acid chemically linked to (a) the liver X receptor agonist or (b) the moiety chemically attached to the liver X receptor agonist.
18 . The method of claim 17 , wherein the antibody has a heavy chain sequence having at least about 90% sequence identity to SEQ ID NO. 10.
19 . The method of claim 12 , wherein the leukocyte is in a subject having a disease or condition selected from atherosclerosis, diabetes, inflammation, and Alzheimer's disease.
20 . The method of claim 12 , wherein the antibody drug conjugate has the structure I: