IP Library › Granted Patent US 12,264,336
Granted Patent B2
US 12,264,336 · App. 17/554,531 · Granted Apr 1, 2025

Platform for generating safe cell therapeutics

Inventors: Richard Klemke (La Jolla, CA); Huawei Wang (San Diego, CA)
Assignee: The Regents of the University of California
C12N5/0662A61K9/0019A61K35/12A61K35/17A61K35/28A61K38/2066A61K38/208A61K39/001102A61K39/215A61P35/00C12N5/0646C12N5/0667C12N5/10C12N15/85C12N15/88A61K39/00A61K2039/515A61K2039/545C12N2501/999C12N2510/00C12N2513/00
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Quick Facts
Patent No.
US 12,264,336
App. No.
17/554,531
Granted
Apr 1, 2025
Kind
B2
Abstract

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.

Claims (29)

1. A method for treating cancer or a neoplasm in a subject, the method comprising:

administering to a subject a cell without a nucleus, wherein the cell without the nucleus comprises a virus, wherein the virus comprises an exogenous nucleic acid molecule comprising a sequence encoding a therapeutic agent for the treatment of the cancer or the neoplasm, wherein the cell without the nucleus delivers the virus to a cancer cell or a neoplasm cell in the subject, thereby treating the cancer or the neoplasm in the subject, wherein the cell without the nucleus is derived from a nucleated parent cell, and wherein the nucleated parent cell comprises a mesenchymal stromal cell.

2. The method of claim 1 , wherein the virus is a replicating virus.

3. The method of claim 1 , wherein the virus is an oncolytic virus.

4. The method of claim 1 , wherein the virus is a vesicular stomatitis virus (VSV).

5. The method of claim 1 , wherein the exogenous nucleic acid molecule comprises at least a portion of a viral genome of the virus.

6. The method of claim 1 , wherein the cell without the nucleus further comprises a second therapeutic agent that comprises or is encoded by a second exogenous nucleic acid molecule.

7. The method of claim 6 , wherein the second exogenous nucleic acid molecule comprises a ribonucleic acid (RNA).

8. The method of claim 7 , wherein the RNA is a messenger (mRNA) encoding a therapeutic polypeptide or protein.

9. The method of claim 6 , wherein the cell without the nucleus expresses a therapeutic polypeptide from the second exogenous nucleic acid molecule in absence of the nucleus.

10. The method of claim 6 , further comprising secreting the second therapeutic agent from the cell without the nucleus.

11. The method of claim 1 , wherein the therapeutic agent comprises an anti-programmed death-1 (PD1) antibody or antigen-binding fragment, or an anti-programmed death-ligand 1 (PD-L1) antibody or antigen-binding fragment.

12. The method of claim 1 , wherein the therapeutic agent comprises a cytokine.

13. The method of claim 12 , wherein the cytokine comprises interleukin 12 (IL-12).

14. The method of claim 1 , wherein the cell without the nucleus further comprises a chemokine receptor.

15. The method of claim 14 , wherein the chemokine receptor comprises C-X-C motif chemokine receptor 2 (CXCR2), C-X-C motif chemokine receptor 4 (CXCR4), C-C motif chemokine receptor 2 (CCR2), C-X-C motif chemokine receptor 3 (CXCR3), or any combination thereof.

16. The method of claim 1 , wherein the cell without the nucleus further comprises an adhesion molecule.

17. The method of claim 16 , wherein the adhesion molecule comprises P-selectin glycoprotein ligand-1 (PSGL-1).

18. The method of claim 1 , wherein the cell without the nucleus further comprises an immune-evading moiety comprising CD47.

19. The method of claim 1 , wherein the administering comprises administering intraarterially the cell without the nucleus to the subject.

20. The method of claim 1 , wherein the administering comprises administering the cell without the nucleus to the subject systemically.

21. The method of claim 1 , wherein the administering is performed at least once a day.

22. The method of claim 1 , wherein the administering is performed at least once every three days.

23. The method of claim 1 , wherein the cancer is breast cancer.

24. The method of claim 1 , wherein the cancer is a glioblastoma.

25. The method of claim 1 , wherein the cell without the nucleus does not differentiate in vivo.

26. The method of claim 1 , wherein the cell without the nucleus has a diameter comprising between about 5 micrometer (μm) to about 20 μm.

27. The method of claim 1 , wherein the cell without the nucleus is derived from a nucleated parent cell, and has a diameter that is about 60% of the diameter of the nucleated parent cell.

28. The method of claim 1 , wherein the cell without the nucleus is contained in a pharmaceutical formulation comprising a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 22, 2021
From: KLEMKE, RICHARD; WANG, HUAWEI
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 058457/0110 →
Continuity (5)
Continuation 17159595 · Jan 27, 2021
Continuation 16902420 · Jun 16, 2020
Continuation 16636249
Provisional Application 62542133 · Aug 7, 2017
Related Publication 20220177847A1 · Jun 9, 2022
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