In situ antigen-generating cancer vaccine

• US 10,406,216 B2
• Filed: 11/07/2016
• Issued: 09/10/2019
• Est. Priority Date: 06/03/2011
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Kim, Jaeyun, Mooney, David J., Li, Weiwei Aileen, Arany, Praveen, Gadish, Or
• Primary Examiner(s): Aeder, Sean E
• Application Number:
  US15/345,131
• Publication Number:
  US 20170182138A1
• Time in Patent Office: 1,037 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 2039/5154 Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55511 Organic adjuvants
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2039/572 cytotoxic response
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The invention provides compositions and methods for utilizing scaffolds in cancer vaccines.

Claims

1. A biopsy-free method for producing a processed tumor antigen in situ comprising

administering to a subject having a cancer comprising circulating tumor cells a porous 3-dimensional scaffold that does not comprise a tumor antigen before the scaffold is administered to the subject, said scaffold comprising

(a) a chemoattractant for a cancer cell, wherein the chemoattractant for the cancer cell is released from the scaffold with a first release profile;

and

(b) an immune cell recruitment composition, wherein the immune cell recruitment composition is released from the scaffold with a second release profile, such that cancer cells are recruited to the scaffold prior to recruitment of immune cells;

maintaining the scaffold in situ for a period of time sufficient to accumulate circulating cancer cells, to yield a cancer cell-containing scaffold; and

contacting said cancer cell-containing scaffold with a cytotoxic or cytolytic element to produce a processed tumor antigen, wherein the scaffold recruits an immune cell to the site of the processed tumor antigen after the processed tumor antigen is produced.

2. The method of claim 1, wherein said cytotoxic element comprises application of external heat, ultrasound, laser radiation, or gamma radiation to said cell-containing scaffold.

3. The method of claim 1, wherein said scaffold further comprises a hyperthermia-inducing composition.

11. The method of claim 1, wherein the immune cell comprises a dendritic cell.

12. The method of claim 1, wherein the chemoattractant for a cancer cell is a chemokine.

13. The method of claim 12, wherein the chemoattractant for a cancer cell is selected from the group consisting of CCL-21, CCL-19, SDF-1, VEGF, and IL-4.

14. The method of claim 12, wherein the chemoattractant for a cancer cell is CCL-21.

15. The method of claim 1, wherein the immune cell recruitment composition comprises GM-CSF.

16. The method of claim 1, wherein the scaffold further comprises CpG oligodeoxynucleotides (CpG-ODN).

17. The method of claim 3, wherein the hyperthermia-inducing composition comprises a magnetic nanoparticle or a near infrared (NIR) absorbing nanoparticle.

18. The method of claim 17, wherein the hyperthermia-inducing composition comprises a magnetic nanoparticle, and wherein said cytotoxic or cytolytic element comprises an alternative magnetic field.

19. The method of claim 17, wherein the hyperthermia-inducing composition comprises a NIR absorbing nanoparticle, and wherein said cytotoxic or cytolytic element comprises NIR radiation.

20. The method of claim 17, wherein the hyperthermia-inducing composition comprises a NIR absorbing nanoparticle selected from the group consisting of a gold nanorod, a gold nanoshell, a gold nanocage, a noble metal nanoparticle, a carbon nanotube, a carbon nanoparticle, and a graphite nanoparticle.

21. The method of claim 20, wherein the hyperthermia-inducing composition comprises a gold nanorod or a gold nanoshell.

22. The method of claim 1, wherein the scaffold comprises a first polymer comprising the chemoattractant, and a second polymer comprising the immune cell recruitment composition.

23. The method of claim 22, wherein the first polymer has a different degradation profile than the second polymer.

24. The method of claim 1, wherein the cancer comprises metastatic cancer cells.

25. The method of claim 1, wherein the cancer is a blood-borne cancer.

26. The method of claim 25, wherein the cancer is leukemia.

27. The method of claim 1, wherein the subject is a human subject.

4. A polymer vaccine scaffold device that first recruits a cancer cell that is destroyed to generate a lysate, and subsequently recruits a dendritic cell, wherein the device comprises

(a) a cytotoxicity-inducing composition,

(b) a chemoattractant for a cancer cell, wherein the chemoattractant for the cancer cell is released from the scaffold with a first release profile;

and

(c) an immune cell recruitment composition, wherein the immune cell recruitment composition is released from the scaffold with a second release profile, such that cancer cells are recruited to the scaffold prior to recruitment of immune cells following administration of the device to a subject;

wherein said device does not comprise a tumor antigen before said device is administered to the subject.

5. A biopsy-free method for producing a processed tumor antigen in situ comprising administering to a subject diagnosed with a cancer the device of claim 4, thereby producing a processed tumor antigen in situ in the subject.

6. A method of treating cancer in a subject in need thereof, comprising administering the device of claim 4 to the subject, thereby treating cancer in the subject.

7. A method of activating an immune cell in a subject in need thereof, comprising administering the device of claim 4 to the subject and, after a period of time sufficient for the device to accumulate circulating cancer cells, irradiating the site of administration with a laser.

8. The method of claim 7, wherein said immune cell comprises a dendritic cell.

9. The method of claim 7, wherein the device is administered by implantation into said subject.

10. The method of claim 9, wherein said implantation comprises subcutaneous implantation.

28. The device of claim 4, wherein the chemoattractant for a cancer cell is a chemokine.

29. The device of claim 4, wherein the chemoattractant for a cancer cell is selected from the group consisting of CCL-21, CCL-19, SDF-1, VEGF, and IL-4.

30. The device of claim 4, wherein the chemoattractant for a cancer cell is CCL-21.

31. The device of claim 4, wherein the immune cell recruitment composition comprises GM-CSF.

32. The device of claim 4, wherein the second polymer composition further comprises CpG oligodeoxynucleotides (CpG-ODN).

33. The device of claim 4, wherein the cytotoxicity-inducing composition comprises a hyperthermia-inducing particle.

34. The device of claim 33, wherein the wherein the hyperthermia-inducing particle comprises a magnetic nanoparticle or a near infrared (NIR) absorbing nanoparticle.

35. The device of claim 33, wherein the hyperthermia-inducing particle comprises a NIR absorbing nanoparticle selected from the group consisting of a gold nanorod, a gold nanoshell, a gold nanocage, a noble metal nanoparticle, a carbon nanotube, a carbon nanoparticle, and a graphite nanoparticle.

36. The device of claim 33, wherein the hyperthermia-inducing particle comprises a gold nanoparticle or a gold nanorod.

37. The device of claim 4, wherein the device comprises a first polymer comprising the chemoattractant, and a second polymer comprising the immune cell recruitment composition.

38. The device of claim 37, wherein the first polymer has a different degradation profile than the second polymer.