In situ antigen-generating cancer vaccine

• US 9,486,512 B2
• Filed: 06/04/2012
• Issued: 11/08/2016
• 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:
  US14/123,615
• Publication Number:
  US 20140193488A1
• Time in Patent Office: 1,618 Days
• Field of Search: None
• US Class Current: 1/1
• 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 diagnosed with a cancer a porous 3-dimensional scaffold, said scaffold comprising

(a) a first zone comprising a chemoattractant of cancer cells and a cytotoxicity-inducing composition, and

(b) a second zone comprising an immune cell recruitment composition, wherein said second zone does not comprise a cytotoxicity-inducing composition;

and

maintaining said scaffold in situ for a time period sufficient to accumulate a circulating cancer cell to yield a cancer cell-containing scaffold, and

contacting said cytotoxicity-inducing composition in said first zone with a cytotoxic or cytolytic element to specifically disrupt said cancer cell, thereby producing a processed tumor antigen.

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 2, wherein said laser radiation comprises ultraviolet or near infrared laser radiation.

4. The method of claim 1, wherein said cytotoxicity-inducing composition comprises a hyperthermia-inducing composition.

5. The method of claim 4, wherein said hyperthermia-inducing composition comprises a magnetic nanoparticle or a near infrared (NIR) absorbing nanoparticle.

6. The method of claim 5, wherein said nanoparticle is magnetic, and wherein said method comprises contacting said magnetic nanoparticle with said cytotoxic or cytolytic element to induce local hyperthermia in situ, thereby disrupting said cancer cell and producing a processed tumor antigen, wherein said cytotoxic or cytolytic element is an alternative magnetic field.

7. The method of claim 5, wherein said NIR nanoparticle is selected from the group consisting of a gold nanorod, gold nanoshell, gold nanocage, noble metal nanoparticle, carbon nanotube, carbon nanoparticle, and graphite nanoparticle, and wherein said method comprises contacting said NIR nanoparticle with said cytotoxic or cytolytic element to induce local hyperthermia in situ, thereby disrupting said cancer cell and producing a processed tumor antigen, wherein said cytotoxic or cytolytic element is NIR radiation.

8. The method of claim 1, wherein said chemoattractant of cancer cells comprises a chemokine selected from the group consisting of CCL-21, CCL-19, SDF-1, VEGF, and IL-4.

9. The method of claim 1, wherein said cancer is characterized by circulating tumor cells.

10. The method of claim 1, wherein said subject is diagnosed with a metastatic cancer condition or a leukemia.

16. The method of claim 1, further comprising maintaining said scaffold in situ for a time period sufficient to accumulate a circulating immune cell to yield a cancer cell-and immune cell-containing scaffold prior to contacting said cytotoxicity-inducing composition in said first zone with a cytotoxic or cytolytic element to specifically disrupt a cancer cell, thereby producing a processed tumor antigen.

17. The method of claim 1, wherein said immune cell recruitment composition comprises granulocyte macrophage colony-stimulating factor.

18. The method of claim 17, wherein said immune cell is a dendritic cell.

19. The method of claim 18, wherein said second zone further comprises a danger signal for dendritic cells.

20. The method of claim 1, wherein said first zone is configured as a core and said second zone is configured as a shell.

21. The method of claim 1, wherein said first zone and said second zone are layered.

23. The method of claim 1, wherein said first zone comprises compartments within said porous 3-dimensional scaffold.

11. A tumor antigen-processing device comprising a porous 3-dimensional scaffold, said scaffold comprising

(a) a first zone comprising a chemoattractant of cancer cells and a cytotoxicity-inducing composition, and

(b) a second zone comprising an immune cell recruitment composition, wherein said second zone does not comprise a cytotoxicity-inducing composition.

12. The device of claim 11, wherein said cytotoxicity-inducing composition comprises a hyperthermia-inducing particle.

13. The device of claim 11, wherein said cytotoxicity-inducing composition comprises a gold nanoparticle or a gold nanorod.

14. The device of claim 11, wherein said immune cell recruitment composition comprises granulocyte macrophage colony-stimulating factor.

15. The device of claim 11, wherein said first zone is configured as a core and said second zone is configured as a shell.

22. The device of claim 11, wherein said first zone and said second zone are layered.

24. The device of claim 11, wherein said first zone comprises compartments within said porous 3-dimensional scaffold.