Continuous cell programming devices

• US 10,258,677 B2
• Filed: 04/21/2016
• Issued: 04/16/2019
• Est. Priority Date: 02/13/2008
• Status: Active Grant

• Current Assignee: Dana-Farber Cancer Institute, President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: Dana-Farber Cancer Institute, President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Mooney, David J., Ali, Omar Abdel-Rahman, Dranoff, Glenn
• Primary Examiner(s): Allen, Marianne P
• Application Number:
  US15/135,255
• Publication Number:
  US 20160220667A1
• Time in Patent Office: 1,090 Days
• Field of Search: None
• 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 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/55588 Adjuvants of undefined constitution
• CPC Class Codes: A61K 2039/6093 Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/708 having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• 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 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants

Abstract

The present invention comprises compositions, methods, and devices for creating an infection-mimicking environment within a polymer scaffold to stimulate antigen-specific dendritic cell activation. Devices of the present invention are used to provide protective immunity to subjects against infection and cancer.

Claims

1. A device comprising

a scaffold polymer selected from the group consisting of poly-lactide-co-glycolide (PLG), alginate, xanthan gum, gellan, or emulsan;

a tumor antigen;

a recruitment composition comprising a cytokine, which comprises a granulocyte macrophage colony stimulating factor (GM-CSF), that recruits one or more dendritic cells to temporarily reside within said device; and

a positively charged polyethylenimine (PEI)-condensed toll-like receptor-9 (TLR-9)-activating CpG-ODN (PEI-CpG-ODN) which is retained in or on said scaffold polymer,

wherein said PEI-CpG-ODN is present in an amount effective to overcome the trapping effect of the cytokine on said dendritic cells.

2. The device of claim 1, wherein the recruitment composition is encapsulated.

3. The device of claim 1, wherein said tumor antigen comprises a biopsy tumor cell lysate.

4. The device of claim 1, wherein the scaffold polymer is alginate.

5. The device of claim 1, wherein the scaffold polymer is PLG.

6. The device of claim 1, wherein the CpG-ODN is CpG-ODN 1826.

7. The device of claim 1, wherein said PEI-CpG-ODN comprises nanoparticles.

8. The device of claim 1, wherein said PEI-CpG-ODN is retained in said scaffold polymer.