Methods and compositions for immunomodulation
Provided are cells containing exogenous antigen and uses thereof.
1. An engineered enucleated erythroid cell comprising at least one exogenous antigen polypeptide selected from the group consisting of CD19, CD20, CD123, CD33, CD133, CD138, CD5, CD7, CD22, and CD30, or an extracellular domain thereof,
wherein:
the at least one exogenous antigen polypeptide is on the extracellular surface of the engineered enucleated erythroid cell; and
the engineered enucleated erythroid cell was produced by a process comprising:
introducing a transgene encoding the at least one exogenous antigen polypeptide into the nucleated erythroid cell precursor; and
culturing the nucleated erythroid cell precursor under conditions suitable for enucleation of the nucleated erythroid cell precursor and production of the at least one exogenous antigen polypeptide.
2. The engineered enucleated erythroid cell of claim 1 , wherein the engineered enucleated erythroid cell comprises at least 1,000 copies of the at least one exogenous antigen polypeptide.
3. The engineered enucleated erythroid cell of claim 1 , wherein the engineered enucleated erythroid cell comprises at least 10,000 copies of the at least one exogenous antigen polypeptide.
4. The engineered enucleated erythroid cell of claim 1 , wherein the at least one exogenous antigen polypeptide comprises full length CD19 polypeptide.
5. The engineered enucleated erythroid cell of claim 1 , wherein the at least one exogenous antigen polypeptide comprises an extracellular domain of CD19 polypeptide.
6. The engineered enucleated erythroid cell of claim 5 , wherein the at least one exogenous antigenic polypeptide is a fusion protein further comprising a transmembrane domain of an endogenous erythroid membrane protein.
7. The engineered enucleated erythroid cell of claim 6 , wherein the endogenous erythroid membrane protein is glycophorin A.
8. The engineered enucleated erythroid cell of claim 1 , wherein the engineered enucleated erythroid cell is not a hypotonically dialysed cell.
9. The engineered enucleated erythroid cell of claim 1 , wherein the engineered enucleated erythroid cell is a reticulocyte.
10. The engineered enucleated erythroid cell of claim 1 , wherein the engineered enucleated erythroid cell is an erythrocyte.
11. The engineered enucleated erythroid cell of claim 1 , wherein the nucleated erythroid cell precursor is a CD34 + hematopoietic stem cell.
12. The engineered enucleated erythroid cell of claim 1 , wherein the engineered enucleated erythroid cell is a human cell.
13. A pharmaceutical composition comprising a population of the engineered enucleated erythroid cells of claim 1 .
14. The pharmaceutical composition of claim 13 , wherein at least 60% of cells in the pharmaceutical composition are the engineered enucleated erythroid cells.
15. The engineered enucleated erythroid cell of claim 1 , wherein the at least one exogenous antigenic polypeptide is a fusion protein.
16. The engineered enucleated erythroid cell of claim 15 , wherein the fusion protein further comprises a transmembrane domain of an endogenous erythroid membrane protein.
17. The engineered enucleated erythroid cell of claim 16 , wherein the endogenous erythroid membrane protein is glycophorin A.
18. The engineered enucleated erythroid cell of claim 1 , wherein the at least one exogenous antigen polypeptide comprises an extracellular domain of CD20 polypeptide.
19. The engineered enucleated erythroid cell of claim 18 , wherein the at least one exogenous antigenic polypeptide is a fusion protein further comprising a transmembrane domain of an endogenous erythroid membrane protein.
20. The engineered enucleated erythroid cell of claim 19 , wherein the endogenous erythroid membrane protein is glycophorin A.