Protein modification of living cells using sortase
Non-genetically engineered mammalian cells modified by sortase-mediated conjugation of an agent thereto are provided. Methods of conjugating agents to non-genetically engineered mammalian cells using sortase are provided. Methods of using the cells, e.g., for diagnostic and/or therapeutic purposes, are provided.
1. A human cell having an agent linked thereto via a sortase recognition sequence, wherein the agent is linked to an endogenous, non-genetically engineered protein of the human cell, and wherein the human cell has not been genetically engineered to express a protein comprising a sortase recognition sequence, and wherein the agent comprises an antigen presenting molecule.
2. The human cell of claim 1 , wherein the human cell is a cellular artificial antigen presenting cell (aAPC).
3. The human cell of claim 1 , wherein the agent comprises an antigen, and wherein the antigen is a tumor antigen, a viral antigen, a bacterial antigen, a fungal antigen, or a parasite antigen.
4. The human cell of claim 1 , wherein the human cell is a hematopoietic stem cell (HSC).
5. The human cell of claim 1 , wherein the human cell is a myeloid progenitor cell.
6. The human cell of claim 1 , wherein the human cell is a lymphoid progenitor cell.
7. The human cell of claim 1 , wherein the human cell is a red blood cell.
8. The human cell of claim 1 , wherein the human cell is selected from the group consisting of a lymphocyte, a monocyte, a dendritic cell, a macrophage, a neutrophil, a mast cell, an eosinophil, a basophil, and a natural killer (NK) cell.
9. The human cell of claim 1 , wherein the antigen presenting molecules comprise at least a portion of a major histocompatibility (MHC) protein that is capable of binding an antigen.
10. The human cell of claim 9 , wherein the antigen presenting molecules comprise a MHC multimer.
11. The human cell of claim 10 , wherein the antigen presenting molecules comprise a MHC class I protein.
12. The human cell of claim 10 , wherein the antigen presenting molecules comprise an MHC class II protein.
13. The human cell of claim 1 , wherein the antigen presenting molecules comprise a HLA-Ig fusion protein.
14. The human cell of claim 1 , wherein the antigen presenting molecules comprise TCR-engaging molecules.
15. The human cell of claim 1 , wherein the sortase recognition sequence comprises LPXTG.
16. A method of modulating an immune response of a subject to an entity of interest, the method comprising administering to the subject the human cell of claim 1 .
17. A method of treating a subject in need of treatment for a disease, the method comprising administering to the subject the human cell of claim 1 .
18. The method of claim 17 , wherein the disease comprises an infectious disease, cancer, an autoimmune disease, an allergy, an inflammatory condition, or an immunodeficiency.