Mutant variants of PD-1 receptor with selective binding to PD-L1 and uses thereof
Disclosed are human Programmed Cell Death-1 (PD-1) receptor mutants having selectivity for PD-L1 compared to PD-L2, methods of obtaining the mutants, and uses of the mutants for treatment and imaging.
1. A human Programmed Cell Death-1 (PD-1) receptor mutant comprising at least the first 149 consecutive amino acids of SEQ ID NO:1 with mutation Y68R or Y68K, wherein the mutant has selectivity for PD-LI compared to PD-L2 and wherein the mutant has undetectable PD-L2 binding.
2. A fusion polypeptide comprising the PD-1 receptor mutant of claim 1 fused to an immunoglobulin domain polypeptide.
3. The fusion polypeptide of claim 2 , wherein the mutant is fused to the immunoglobulin domain polypeptide by a peptide bond between a terminal amino acid of the mutant and a terminal amino acid of the immunoglobulin domain polypeptide.
4. The fusion polypeptide of claim 2 , wherein the immunoglobulin domain polypeptide comprises an immunoglobulin IgG1 Fc domain.
5. The fusion polypeptide of claim 4 , wherein the immunoglobulin IgG1 Fc domain is human.
6. A composition comprising the PD-1 receptor mutant of claim 4 , and a pharmaceutically acceptable carrier.
7. The PD-1 receptor mutant of claim 1 further comprising a radiolabel.
8. A method of imaging a PD-L1 positive tumor in a subject comprising administering the radiolabeled PD-1 receptor mutant of claim 7 to the subject, where the mutant binds to the tumor, and imaging the radiolabeled mutant bound to the tumor.
9. A method of stimulating T cell activation, treating a tumor, or treating an infection in a subject comprising administering to the subject a human Programmed Cell Death-1 (PD-1) receptor mutant comprising at least the first 149 consecutive amino acids of SEQ ID NO: 1 with mutation Y68R or Y68K, wherein the mutant has selectivity for PD-LI compared to PD-L2 and wherein the mutant has undetectable PD-L2 binding, or a fusion polypeptide comprising the PD-1 receptor mutant fused to an immunoglobulin domain polypeptide, or a composition comprising the PD-1 receptor mutant or the fusion polypeptide, in an amount effective to stimulate T cell activation, treat a tumor, or treat an infection, respectively, in a subject.
10. The method of claim 9 , wherein the T cell activation comprises cytokine secretion.
11. The method of claim 9 , wherein the subject has a tumor.
12. The method of claim 9 , wherein the subject has an infection.