Therapeutic peptides
The present disclosure provides, in part, compositions comprising an antibody or antibody fragment that immunospecifically binds to MCH class I polypeptide-related sequence A (MICA), or an epitope thereof.
1. A composition comprising an isolated antibody or antibody fragment that immunospecifically binds to human MHC class I polypeptide-related sequence A (MICA), wherein the antibody or antibody fragment comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), wherein the V H complementarity determining region (CDR) 1 comprises the amino acid sequence set forth in SEQ ID NO: 153, the V H CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 156, the V H CDR3 comprises the amino acid sequence set forth in SEQ ID NO:158, the V L CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 160, the V L CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 162 and the V L CDR3 comprises the amino acid sequence set forth in SEQ ID NO:164.
2. The composition of claim 1 , further comprising an anti-cancer therapeutic.
3. The composition of claim 1 , formulated as a pharmaceutical composition.
4. The composition of claim 1 , further comprising an histone deacetylase inhibitor (HDAC) selected from the group consisting of suberoylanilide hydroxamic acid (SAHA), trichostatin A (TSA), LAQ824, panobinostat (LBH589), belinostat (PXD101), ITF2357, romidepsin (FK228), entinostat (SNDX-275/MS-275), MGCD0103, valproic acid, phenyl butyrate, AN-9, CHR-3996, and CHR-2845.
5. The composition of claim 1 further comprising a proteasome inhibitor selected from the group consisting of bortezomib, NPI-0052, carfilzomib (PR-171), CEP 18770, and MLN9708.
6. A composition comprising an isolated antibody or antibody fragment that immunospecifically binds to human MHC class I polypeptide-related sequence A (MICA), wherein the antibody or antibody fragment comprises:
(i) a V H comprising the amino acid sequence set forth in SEQ ID NO: 149, and a V L comprising the amino acid sequence set forth in SEQ ID NO: 151;
(ii) a V H comprising the amino acid sequence set forth in SEQ ID NO: 186, and a V L comprising the amino acid sequence set forth in SEQ ID NO: 188; or
(iii) a V H comprising the amino acid sequence set forth in SEQ ID NO: 204, and a V L comprising the amino acid sequence set forth in SEQ ID NO: 206.
7. The composition of claim 1 , further comprising an antibody selected from the group consisting of an anti-CTLA-4 antibody, and anti-PD-1 antibody, an anti-PDL-1 antibody and a combination of one or more thereof.
8. A composition comprising an isolated antibody or antibody fragment that immunospecifically binds to human MHC class I polypeptide-related sequence A (MICA), wherein the antibody or antibody fragment comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), wherein the V H CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 190, the V H CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 192, the V H CDR3 comprises the amino acid sequence set forth in SEQ ID NO:194, the V L CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 197, the V L CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 199, and the V L CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 201.
9. The composition of claim 8 , further comprising an anti-cancer therapeutic.
10. The composition of claim 8 , formulated as a pharmaceutical composition.
11. The composition of claim 8 , further comprising an histone deacetylase inhibitor (HDAC) selected from the group consisting of suberoylanilide hydroxamic acid (SAHA), trichostatin A (TSA), LAQ824, panobinostat (LBH589), belinostat (PXD101), ITF2357, romidepsin (FK228), entinostat (SNDX-275/MS-275), MGCD0103, valproic acid, phenyl butyrate, AN-9, CHR-3996, and CHR-2845.
12. The composition of claim 8 , further comprising a proteasome inhibitor selected from the group consisting of bortezomib, NPI-0052, carfilzomib (PR-171), CEP 18770, and MLN9708.
13. A composition comprising an isolated antibody or antibody fragment that immunospecifically binds to human MHC class I polypeptide-related sequence A (MICA), wherein the antibody or antibody fragment comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), wherein the V H CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 208, the V H CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 210, the V H CDR3 comprises the amino acid sequence set forth in SEQ ID NO:212, the V L CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 215, the V L CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 217, and the V L CDR3 comprises the amino acid sequence set forth in SEQ ID NO:219.
14. The composition of claim 13 , further comprising an anti-cancer therapeutic.
15. The composition of claim 13 , formulated as a pharmaceutical composition.
16. The composition of claim 13 , further comprising an histone deacetylase inhibitor (HDAC) selected from the group consisting of suberoylanilide hydroxamic acid (SAHA), trichostatin A (TSA), LAQ824, panobinostat (LBH589), belinostat (PXD101), ITF2357, romidepsin (FK228), entinostat (SNDX-275/MS-275), MGCD0103, valproic acid, phenyl butyrate, AN-9, CHR-3996, and CHR-2845.
17. The composition of claim 13 , further comprising a proteasome inhibitor selected from the group consisting of bortezomib, NPI-0052, carfilzomib (PR-171), CEP 18770, and MLN9708.
18. The composition of claim 6 , further comprising an anti-cancer therapeutic.
19. The composition of claim 6 , formulated as a pharmaceutical composition.
20. The composition of claim 6 , further comprising an histone deacetylase inhibitor (HDAC) selected from the group consisting of suberoylanilide hydroxamic acid (SAHA), trichostatin A (TSA), LAQ824, panobinostat (LBH589), belinostat (PXD101), ITF2357, romidepsin (FK228), entinostat (SNDX-275/MS-275), MGCD0103, valproic acid, phenyl butyrate, AN-9, CHR-3996, and CHR-2845.
21. The composition of claim 6 , further comprising a proteasome inhibitor selected from the group consisting of bortezomib, NPI-0052, carfilzomib (PR-171), CEP 18770, and MLN9708.
22. The composition of claim 6 , further comprising an antibody selected from the group consisting of an anti-CTLA-4 antibody, and anti-PD-1 antibody, an anti-PDL-1 antibody and a combination of one or more thereof.
23. The composition of claim 8 , further comprising an antibody selected from the group consisting of an anti-CTLA-4 antibody, and anti-PD-1 antibody, an anti-PDL-1 antibody and a combination of one or more thereof.
24. The composition of claim 13 , further comprising an antibody selected from the group consisting of an anti-CTLA-4 antibody, and anti-PD-1 antibody, an anti-PDL-1 antibody and a combination of one or more thereof.