Targeted Immunotolerance

Abstract

Methods and compounds for conferring site-specific or local immune privilege.

1 - 74 . (canceled) 
     
     
         75 . A therapeutic compound comprising a PD-1 agonist antibody and a targeting moiety that binds to a target molecule on a kidney cell or a pancreatic cell. 
     
     
         76 . The therapeutic compound of  claim 75 , wherein the target molecule is a cadherin. 
     
     
         77 . The therapeutic compound of  claim 75 , wherein the target molecule on the kidney cell is COL1A1, cadherin 2, VCAM-1, Thy1, Podocin, KIM1, PLA2R, OAT1, OCT2, K-cadherin 6. 
     
     
         78 . The therapeutic compound of  claim 77 , wherein the target molecule is OCT2. 
     
     
         79 . The therapeutic compound of  claim 75 , wherein the target molecule on the pancreatic cell is SEZ6L2, LRP11, DISP2, SLC30A8, FXYD2 TSPAN7, TMEM27, FXYD2, GPR119, HEPACAM2. 
     
     
         80 . The therapeutic compound of  claim 79 , wherein the target molecule is TSPAN7. 
     
     
         81 . The therapeutic compound of  claim 75 , wherein the target molecule is a target molecule on the kidney cell. 
     
     
         82 . The therapeutic compound of  claim 75 , wherein the target molecule is a target molecule on the pancreatic cell. 
     
     
         83 . A therapeutic compound having the formula from N-terminus to C-terminus:
 Chain 1: [VH1-CH1]-[CH2-CH3]-Linker A-scFv;   Chain 2: [VH1-CH1]-[CH2-CH3]-Linker A-scFv;   Chain 3: [VL1-CL]; and   Chain 4: [VL1-CL];   wherein chains 1 and 2 are identical to each other, and chains 3 and 4 are identical to each other;   wherein chain 1 forms a homodimer with chain 2, and chain 3 and 4 associate with each VH1-CH1 domain of chain 1 and chain 2 to form two functional Fab units; wherein CH2-CH3 comprises the Fc region;   wherein each Fab unit is an anti-PD-1 agonist antibody and each scFv unit is a scFv that binds to a target molecule on a kidney cell or a pancreatic cell;   wherein each scFv unit has the formula of 5′-VL2-Linker B-VH2-3′, or 5′-VH2-Linker B-VL2-3′,   wherein Linker A and Linker B are each, independently, a peptide linker.   
     
     
         84 . The therapeutic compound of  claim 83 , wherein the target molecule is a cadherin. 
     
     
         85 . The therapeutic compound of  claim 83 , wherein the target molecule on the kidney cell is COL1A1, Cadherin 2, VCAM-1, Thy1, Podocin, KIM1, PLA2R, OAT1, OCT2, K-cadherin 6. 
     
     
         86 . The therapeutic compound of  claim 85 , wherein the target molecule is OCT2. 
     
     
         87 . The therapeutic compound of  claim 83 , wherein the target molecule on the pancreatic cell is SEZ6L2, LRP11, DISP2, SLC30A8, FXYD2 TSPAN7, TMEM27, FXYD2, GPR119, HEPACAM2. 
     
     
         88 . The therapeutic compound of  claim 87 , wherein the target molecule is TSPAN7. 
     
     
         89 . The therapeutic compound of  claim 83 , wherein the target molecule is a target molecule on the kidney cell. 
     
     
         90 . The therapeutic compound of  claim 83 , wherein the target molecule is a target molecule on the pancreatic cell. 
     
     
         91 . A method of treating a subject having an autoimmune disorder that affects the kidney or the pancreas of the subject, the method comprising administering a therapeutically effective amount of a therapeutic compound of  claim 75 . 
     
     
         92 . The method of  claim 91 , wherein the autoimmune disorder is Type I diabetes, Focal Segmented Glomerular Sclerosis (FSGS) and other diseases that can affect kidney for example lupus nephritis, systemic scleroderma, membranous glomerular nephropathy (MGN), Membranous nephropathy (MN), Minimal Change Disease (MCD), IgA nephropathy, or ANCA-associated vasculitis (AAV). 
     
     
         93 . A method of treating a subject having an autoimmune disorder that affects the kidney or the pancreas of the subject, the method comprising administering a therapeutically effective amount of a therapeutic compound of  claim 83 . 
     
     
         94 . The method of  claim 93 , wherein the autoimmune disorder is Type I diabetes, Focal Segmented Glomerular Sclerosis (FSGS) and other diseases that can affect kidney for example lupus nephritis, systemic scleroderma, membranous glomerular nephropathy (MGN), Membranous nephropathy (MN), Minimal Change Disease (MCD), IgA nephropathy, or ANCA-associated vasculitis (AAV).