Combination vaccine devices and methods of killing cancer cells

• US 10,682,400 B2
• Filed: 04/30/2015
• Issued: 06/16/2020
• Est. Priority Date: 04/30/2014
• Status: Active Grant

• Current Assignee: Dana-Farber Cancer Institute, President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Ali, Omar Abdel-Rahman, Mooney, David J., Dranoff, Glenn
• Primary Examiner(s): Reddig, Peter J
• Application Number:
  US15/303,985
• Publication Number:
  US 20170042995A1
• Time in Patent Office: 1,874 Days
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/64 characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001102 Receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: A61K 39/001156 Tyrosinase and tyrosinase related proteinases [TRP-1 or TRP-2]
• CPC Class Codes: A61K 39/001157 Telomerase or TERT [telomerase reverse transcriptase]
• CPC Class Codes: A61K 39/00117 Mucins, e.g. MUC-1
• CPC Class Codes: A61K 39/001171 Gangliosides, e.g. GM2, GD2 or GD3
• CPC Class Codes: A61K 39/00118 from embryonic or fetal origin
• CPC Class Codes: A61K 39/001182 Carcinoembryonic antigen [CEA]
• CPC Class Codes: A61K 39/001186 MAGE
• CPC Class Codes: A61K 39/001191 Melan-A/MART
• CPC Class Codes: A61K 39/001192 Glycoprotein 100 [Gp100]
• CPC Class Codes: A61K 39/02 Bacterial antigens
• CPC Class Codes: A61K 39/12 : Viral antigens
• CPC Class Codes: A61K 39/39 : characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/3955 : against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 47/34 : Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/36 : Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 : against CD28 or CD152
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 16/3053 : Skin, nerves, brain
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

The present invention comprises compositions, methods, and devices for enhancing an endogenous immune response against a cancer. Devices and methods provide therapeutic immunity to subjects against cancer.

Claims

1. A method of killing a cancer cell in a tumor in a subject in need thereof comprising administering to the subject:

a) an inhibitor comprising an antibody, or an antigen binding fragment thereof, against an immune checkpoint protein; and

b) a device comprising

i) a macroporous scaffold composition comprising open, interconnected pores wherein the scaffold comprises a hydrogel or porous polymer;

ii) a cell recruitment composition capable of recruiting an immune cell, wherein the cell recruitment composition is selected from the group consisting of a cytokine, a chemokine, a growth factor, and a combination thereof; and

iii) a bioactive composition, wherein the bioactive composition is incorporated into or coated onto the scaffold composition, and wherein the bioactive composition comprises a cancer cell, a cancer antigen, or a cancer derived antigen,

wherein the inhibitor is administered prior to and subsequent to the administration of the device, and wherein the method enhances the CD8 T cell;

Treg cell ratio in the tumor, thereby killing a cancer cell in the tumor.

2. The method of claim 1, wherein migration of the immune cells to another site in the body is promoted by the open, interconnected macropores and by a deployment signal.

3. The method of claim 2, wherein the other site in the body is a nearby or remote tissue target.

4. The method of claim 1, wherein the inhibitor is also present in or on the device.

5. The method of claim 4, wherein the inhibitor is also coated in or on the scaffold composition.

6. The method of claim 1, wherein the inhibitor is not present in or on the device.

7. The method of claim 6, wherein the inhibitor is not coated in or on the scaffold composition.

8. The method of claim 1, wherein the inhibitor is also administered simultaneously with administration of the device.

9. The method of claim 1, wherein the device is implanted subcutaneously into the subject.

10. The method of claim 1, wherein the inhibitor is administered intravenously, intraperitoneally, subcutaneously, orally, intradermally, by inhalation, transmucosally, or rectally.

11. The method of claim 1, wherein the inhibitor is administered by injection, infusion, or inhalation.

12. The method of claim 1, wherein the inhibitor is administered at a dosage of 0.01-10 mg/kg body weight.

13. The method of claim 1, wherein the inhibitor is administered in an amount of 0.01-30 mg per dose.

14. The method of claim 1, wherein the cancer cell is resistant to cytotoxic T-lymphocyte (CTL)-mediated lysis.

15. The method of claim 1, wherein the cancer cell is resistant to natural killer (NK) cell mediated killing.

16. The method of claim 1, wherein the immune checkpoint protein is selected from the group consisting of a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), a programmed cell death protein 1 (PD1), a programmed cell death protein 1 ligand (PDL1), a lymphocyte activation gene 3 (LAG3), a B7-H3, a B7-H4, a T cell membrane protein 3 (TIM3), a 2B4 (CD244), a B and T lymphocyte attenuator (BTLA, CD272), an adenosine A2a receptor (A2aR), a killer cell immunoglobulin-like receptor (KIR), a C-type leptin receptor, and any combination thereof.

17. The method of claim 16, wherein the inhibitor is an antibody selected from the group consisting of an Ipilimumab, a Tremelimumab, an MDX-1106, an MK3475, a CT-011, an MGA271, a fragment thereof, and any combination thereof.

18. The method of claim 16, wherein the immune checkpoint protein is a PD-1.

19. The method of claim 16, wherein the immune checkpoint protein is a CTLA-4.

20. The method of claim 1, wherein the cell recruitment composition further comprises an Flt3L or a CCL20.

21. The method of claim 1, wherein the bioactive composition comprises a cancer antigen.

22. The method of claim 21, wherein the cancer antigen comprises a tumor cell lysate.

23. The method of claim 1, wherein the cancer cell is selected from the group consisting of a melanoma cell, a central nervous system (CNS) cancer cell, a CNS germ cell tumor cell, a lung cancer cell, leukemia cell, multiple myeloma cell, a renal cancer cell, a malignant glioma cell, a medulloblatoma cell, a breast cancer cell, an ovarian cancer cell, a prostate cancer cell, a bladder cancer cell, a fibrosarcoma cell, a pancreatic cancer cell, a gastric cancer cell, a head and neck cancer cell, a colorectal cancer cell, and any combination thereof.

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

25. The method of claim 1, wherein the immune cell is a dendritic cell.

26. The method of claim 1, wherein the device firther comprises an adjuvant.