Engineered PD-1 variants
Isolated polypeptides comprising engineered mutant PD-1 polypeptide are provided, as are fusion polypeptides comprising the mutant and methods of use thereof. Bispecific PD-L1 and PD- L2 binding mutant PD-1 polypeptides are provided. PD-L2-specific binding mutant PD-1 polypeptides are also provided.
1. An isolated mutant programmed cell death 1 (PD-1) polypeptide comprising (i) SEQ ID NO: 2, (ii) SEQ ID NO: 3, or (iii) an amino acid sequence having at least 99% identity to SEQ ID NO: 2 or SEQ ID NO: 3 with the proviso that the mutant PD-1 polypeptide does not comprise SEQ ID NO: 1;
wherein the polypeptide does not comprise (i) SEQ ID NO:_2, wherein position 41 is an A and position 91 is an I, (ii) SEQ ID NO:_3, wherein position 41 is an A and position 91 is an I, or (iii) an amino acid sequence having at least 99% identity to SEQ ID NO:_2 or SEQ ID NO:_3, wherein position 41 is an A and position 91 is an I.
2. The polypeptide of claim 1 , comprising SEQ ID NO: 2.
3. The polypeptide of claim 1 , comprising SEQ ID NO: 3.
4. A fusion polypeptide comprising the polypeptide of claim 1 fused to an immunoglobulin domain polypeptide.
5. The fusion polypeptide of claim 4 , wherein the mutant PD-1 polypeptide is fused to the immunoglobulin domain polypeptide by a peptide bond between a terminal amino acid of the mutant PD-1 polypeptide and a terminal amino acid of the immunoglobulin domain polypeptide.
6. The fusion polypeptide of claim 4 , wherein the immunoglobulin domain polypeptide comprises an immunoglobulin IgG1 Fc domain.
7. The fusion polypeptide of claim 6 , wherein the immunoglobulin IgG1 Fc domain is human.
8. The polypeptide of claim 1 in monovalent form.
9. A homo-oligomer comprising the polypeptide of claim 1 .
10. The homo-oligomer of claim 9 , comprising two polypeptides.
11. A composition comprising the polypeptide of claim 1 .
12. A composition comprising the fusion polypeptide of claim 4 .
13. A composition comprising the homo-oligomer of claim 9 .
14. The composition of claim 11 , comprising a pharmaceutically acceptable carrier.
15. An isolated nucleic acid encoding the isolated mutant PD-1 polypeptide of claim 1 .
16. An isolated nucleic acid encoding the fusion polypeptide of claim 4 .
17. The nucleic acid of claim 15 , which is a recombinant nucleic acid.
18. The nucleic acid of claim 15 , which comprises cDNA.
19. An isolated cell containing a vector comprising a nucleic acid of claim 15 .