Dendritic cell composition

Patent metadata

Field	Value
Publication number	US-10882891-B2
Application number	US-201616065037-A
Country	US
Kind code	B2
Filing date	Dec 22, 2016
Priority date	Dec 23, 2015
Publication date	Jan 5, 2021
Grant date	Jan 5, 2021

Abstract

The present invention contemplates dendritic cell compositions. The dentritic cell compositions employ MHC class-II targeting signals fused to an antigen or fragment thereof to obtain MHC II presentation of the antigen or fragment thereof. In particular, the invention refers to a dendritic cell vaccine comprising dendritic cells expressing a MHC class-II targeting signal fused to an antigen or fragment thereof. Dendritic cell vaccines for the stimulation of an immune response against melanoma-associated antigen are also described.

First claim

The invention claimed is:

1. A dendritic cell composition comprising
A) dendritic cells that express at least one fusion protein, wherein said fusion protein comprises:
i) at least one antigen or a fragment thereof; and
ii) at least one targeting signal sequence, wherein said targeting signal sequence comprises:
a) an endoplasmatic reticulum (ER)-translocation signal sequence preceding the N-terminus of the antigen or fragment thereof; and
b) a transmembrane and cytoplasmic domain comprising an endosomal/lysosomal targeting sequence following the C-terminus of the antigen or fragment thereof;

wherein the targeting signal sequence of a) or b) promotes MHC II presentation of the antigen or fragment thereof; and
B) dendritic cells that express at least one antigen or a fragment thereof, wherein the antigen or fragment thereof is not fused to a targeting signal sequence that promotes MHC II presentation of the antigen or fragment thereof; and
wherein the antigen of A and the antigen of B are the same antigen.

2. The dendritic cell composition according to claim 1 , wherein the fusion protein and the antigen are transiently or stably expressed.

3. The dendritic cell composition according to claim 1 , wherein the fusion protein and the antigen are stably expressed.

4. The dendritic cell composition according to claim 1 , wherein the fusion protein and the antigen are transiently expressed by introducing ivt-RNA.

5. The dendritic cell composition according to claim 1 , wherein the endosomal/lysosomal targeting sequence is derived from DC-LAMP.

6. The dendritic cell composition according to claim 1 , wherein the endosomal/lysosomal targeting sequence is human.

7. The dendritic cell composition according to claim 1 , wherein the endosomal/lysosomal targeting sequence comprises the sequence of SEQ ID NO: 3 or the sequence of SEQ ID NO: 14 or fragments thereof.

8. The dendritic cell composition according to claim 1 , wherein the ER translocation signal sequence is derived from an endosomal/lysosomal associated protein.

9. The dendritic cell composition according to claim 8 , wherein the endosomal/lysosomal associated protein is selected from the group consisting of LAMP1, LAMP2, DC-LAMP, CD68, and CD1b.

10. The dendritic cell composition according to claim 1 , wherein the ER translocation signal sequence is derived from LAMP1.

11. The dendritic cell composition according to claim 1 , wherein the ER translocation signal sequence comprises the sequence of SEQ ID NO: 1 or a fragment thereof.

12. The dendritic cell composition according to claim 1 , wherein the dendritic cells are mature dendritic cells generated by a method comprising the following steps:
(i) providing monocytes;
(ii) incubating the monocytes of step i) with IL-4 and GM-CSF; and
(iii) incubating the monocytes of step ii) with IL-4 and GM-CSF in combination with a maturation cocktail.

13. The dendritic cell composition according to claim 12 , wherein the maturation cocktail comprises at least one of the components selected from the group consisting of IL-ß, TNF-α, IFN-γ, TLR7/8 agonist, PGE2, and TLR3 agonist.

14. The dendritic cell composition according to claim 13 , wherein the maturation cocktail comprises a combination of IL-ß, TNF-α, IFN-γ, TLR7/8 agonist, PGE2, and TLR3 agonist.

15. The dendritic cell composition according to claim 1 , wherein the antigen is MELAN-A.

Assignees

• Medigene Immunotherapies Gmbh
• Helmholtz Zentrum Muenchen Deutsches Forschungszentrum Gesundheit & Umwelt Gmbh

Inventors

• Milosevic Slavoljub
• Ellinger Christian
• Wehner Carina
• Schendel Dolores

Classifications

• A61K40/32

  T-cell receptors [TCR] · CPC title

• C12N5/0639 Primary

  Dendritic cells, e.g. Langherhans cells in the epidermis · CPC title

• A61K40/19

  Dendritic cells · CPC title

• A61K40/4272

  Melan-A/MART · CPC title

• A61K40/4269

  NY-ESO · CPC title