Platform for generating safe cell therapeutics
Provided herein are cytoplasts, compositions comprising cytoplasts, methods of using cytoplasts, and methods of treating a subject, such as providing benefits to a healthy or unhealthy subject, or treating or diagnosing a disease or condition in a subject. In some embodiments, methods of treating a subject include: administering to the subject a therapeutically effective amount of a composition comprising a cytoplast. Also, provided herein are compositions (e.g., pharmaceutical compositions) that include a cytoplast. Also, provided herein are kits comprising instructions for using the compositions or methods.
1. A method of treating cancer in a subject, the method comprising: administering to the subject with cancer a cell without a nucleus, wherein the cell without the nucleus comprises one or more intracellular organelles that synthesizes or secretes an exogenous therapeutic agent in an absence of the nucleus for treatment of the cancer, wherein (i) the one or more intracellular organelles comprises an endoplasmic reticulum or a Golgi apparatus that is endogenous to a parent cell from which the cell without the nucleus was obtained, and (ii) the cell without the nucleus is not an erythrocyte or an erythrocyte precursor.
2. The method of claim 1 , wherein the therapeutic agent comprises an antibody or an antigen-binding fragment thereof.
3. The method of claim 1 , wherein the cancer is in lung tissue.
4. The method of claim 3 , wherein the cell without the nucleus further comprises a homing receptor or cell adhesion molecule that is specific to a ligand expressed on one or more target cells in the lung tissue of the subject.
5. The method of claim 4 , wherein the homing receptor comprises P-selectin glycoprotein ligand-1, C-C Motif Chemokine Receptor 2, or C-X-C Motif Chemokine Receptor 4, or a combination thereof.
6. The method of claim 1 , wherein the cell without the nucleus further comprises a homing receptor that is specific to a ligand expressed on one or more target cells in lymph tissue of the subject.
7. The method of claim 6 , wherein the homing receptor comprises C-X-C chemokine receptor type 3, CD44 antigen, or C-C chemokine receptor type 7, or any combination thereof.
8. The method of claim 1 , wherein the cell without the nucleus comprising the exogenous therapeutic agent delivers the exogenous therapeutic agent to a target tissue in the subject.
9. The method of claim 8 , wherein the cell without the nucleus secretes the exogenous therapeutic agent into extracellular space of a target cell of the target tissue.
10. The method of claim 8 , wherein the target tissue is lung tissue.
11. The method of claim 1 , wherein the cell without the nucleus has a diameter comprising less than or equal to about 100 micrometers.
12. The method of claim 1 , wherein the cell without the nucleus is unable to differentiate or proliferate.
13. The method of claim 1 , wherein the cell without the nucleus is formulated in a pharmaceutical composition comprising a pharmaceutically acceptable: diluent, excipient, or carrier.
14. The method of claim 1 , further comprising removing the cell without the nucleus from cryohibernation or cryopreservation prior to administering the cell to the subject.
15. The method of claim 1 , wherein the cell without the nucleus has a lifespan in the subject of fewer than or equal to about five days.
16. The method of claim 1 , wherein the cell without the nucleus exhibits a viability following cryopreservation as measured at 24 hours following the cryopreservation that is equal to or greater than the viability of a comparable cell without a nucleus that is not cryopreserved.
17. The method of claim 1 , wherein the exogenous therapeutic agent is encoded by an exogenous nucleic acid that is expressed in the cell without the nucleus in the absence of the nucleus.
18. The method of claim 1 , wherein the cell without the nucleus comprises a cytoskeleton that permits the cell without the nucleus to migrate within a target tissue.