MAdCAM targeted immunotolerance
Methods and compounds for conferring site-specific or local immune privilege, such as targeting to a cell expressing MAdCAM.
1. An antibody that binds to MAdCAM, comprising a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 359, the heavy chain CDR2 has the amino acid sequence of SEQ ID NO: 170, and the heavy chain CDR3 has the amino acid sequence of SEQ ID NO:360; and a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 361, the light chain LCDR2 has the amino acid sequence of SEQ ID NO: 362, and the light chain CDR3 has the amino acid sequence of SEQ ID NO: 363.
2. An antibody that binds to MAdCAM, or antigen binding fragment thereof, wherein the antibody, or antigen binding fragment thereof, comprises:
i) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 90, the heavy chain CDR2 has the amino acid sequence of SEQ ID NO: 91, and the heavy chain CDR3 has the amino acid sequence of SEQ ID NO: 92; and a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 93, the light chain CDR2 has the amino acid sequence of SEQ ID NO: 87, and the light chain CDR3 has the amino acid sequence of SEQ ID NO: 94;
ii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 135, the heavy chain CDR2 has the amino acid sequence of SEQ ID NO: 381, and the heavy chain CDR3 has the amino acid sequence of SEQ ID NO: 382; and a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 383, the light chain CDR2 has the amino acid sequence of SEQ ID NO: 384, and the light chain CDR3 has the amino acid sequence of SEQ ID NO: 385; or
iii) a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 359, the heavy chain CDR2 has the amino acid sequence of SEQ ID NO: 170, and the heavy chain CDR3 has the amino acid sequence of SEQ ID NO:360; and a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 361, the light chain LCDR2 has the amino acid sequence of SEQ ID NO: 362, and the light chain CDR3 has the amino acid sequence of SEQ ID NO: 363.
3. The antibody of claim 2 , or antigen binding fragment thereof, wherein the heavy chain variable region and the light chain variable region are in a scFv format.
4. The antibody of claim 2 , or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises
a V K having a sequence of SEQ ID NO: 415 and a V H having a sequence of SEQ ID NO: 414;
a V K of SEQ ID NO: 592 and a V H sequence of SEQ ID NO: 591; or
a V K of SEQ ID NO: 600 and a V H sequence of SEQ ID NO: 599.
5. The antibody of claim 4 , or antigen binding fragment thereof, wherein the V K sequence comprises a sequence of SEQ ID NO: 592 and the V H sequence comprises a sequence of SEQ ID NO: 591.
6. The antibody of claim 2 , or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence has the amino acid sequence SEQ ID NO: 359, the heavy chain CDR2 has the amino acid sequence of SEQ ID NO: 170, and the heavy chain CDR3 has the amino acid sequence of SEQ ID NO:360; and a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence has the amino acid sequence of SEQ ID NO: 361, the light chain LCDR2 has the amino acid sequence of SEQ ID NO: 362, and the light chain CDR3 has the amino acid sequence of SEQ ID NO: 363.
7. The antibody of claim 2 , or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof is linked or associated with an effector molecule.
8. A pharmaceutical composition comprising the antibody of claim 2 .
9. A cell comprising a nucleic acid molecule encoding the antibody of claim 2 .