Combination vaccine devices and methods of killing cancer cells
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.
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.