Dendritic cell composition

{
  "publication_number": "US10882891B2",
  "country": "US",
  "kind": "B2",
  "title": "Dendritic cell composition",
  "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.",
  "claims": [
    "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."
  ],
  "description_excerpt": "The present invention contemplates dendritic cell compositions. The dendritic 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.\n\nIn 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.\n\nDendritic cells represent a very potent agent in immune therapy because they can efficiently prime naive T cells during development of T cell-mediated immunity and stimulate adaptive immune responses. Dendritic cells have the ability to activate immune responses not only against pathogens, but also against malignant cells. In vivo, immature- or intermediate-stage dendritic cells patrol peripheral tissues to capture and process antigens. Under the influence of local cytokines and danger signals, dendritic cells undergo complex maturation processes and migrate to regional lymph nodes, where they form immunological synapses with T cells and present peptides derived from collected antigens in context with MHC class-I or -II molecules. CD4+ T cell activation is dependent on MHC-II complex binding, while CD8+ interaction is dependent on MHC I binding.\n\nThe dendritic cell licensing model describes an indirect CD4 + T cell help for CD8 + T cells by interaction mediated activation that enables dendritic cells to provide costimulatory signals.",
  "cpc": [
    "C07K 14/4748",
    "A61K 2039/5154",
    "A61K 2121/00",
    "A61K 2300/00",
    "A61K 35/17",
    "A61K 38/00",
    "A61K 39/001184",
    "A61K 39/001191",
    "A61K 40/19",
    "A61K 40/24",
    "A61K 40/32",
    "A61K 40/4267",
    "A61K 40/4268",
    "A61K 40/4269",
    "A61K 40/4272",
    "A61P 35/00",
    "C07K 14/7051",
    "C07K 2319/02",
    "C07K 2319/03",
    "C07K 2319/06",
    "C12N 2501/22",
    "C12N 2501/2304",
    "C12N 2501/24",
    "C12N 2502/1114",
    "C12N 2506/115",
    "C12N 2510/00",
    "C12N 5/0638",
    "C12N 5/0639"
  ],
  "ipc": [
    "A61K 39/00",
    "C07K 14/47",
    "C12N 5/0784",
    "A61K 35/17",
    "A61K 38/00",
    "A61P 35/00",
    "C12N 5/0783"
  ],
  "assignees": [
    "Helmholtz Zentrum Muenchen Deutsches Forschungszentrum fuer Gesundheit und Umwelt GmbH",
    "Medigene Immunotherapies GmbH"
  ],
  "inventors": [
    "Slavoljub Milosevic",
    "Christian ELLINGER",
    "Carina WEHNER",
    "Dolores Schendel"
  ],
  "filing_date": "2016-12-22",
  "publication_date": "2021-01-05",
  "grant_date": "2021-01-05",
  "priority_date": "2015-12-23",
  "application_number": "US-201616065037-A",
  "family_id": "57794260",
  "cited_by_count": 4,
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