Targeted immunotolerance
Methods and compounds for conferring site-specific or local immune privilege.
1. 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 MAdCAM;
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.
2. A nucleic acid encoding a therapeutic compound of claim 1 .
3. The therapeutic compound of claim 1 , wherein the Fab unit is a Fab or scFab.
4. The therapeutic compound of claim 1 , wherein the peptide linker comprises glycine, serine, or alanine amino acid residues.
5. The therapeutic compound of claim 1 , wherein the peptide linker is a glycine/serine linker.
6. A therapeutic compound comprising a polypeptide, wherein the polypeptide consists of a polypeptide 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]
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 each scFv unit is a scFv that binds to MAdCAM;
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.
7. A composition comprising a single active therapeutic compound, wherein the single active therapeutic compound is the therapeutic compound of claim 1 .