Peptide display to antigen presenting cells using lipid vehicle
AssigneeTorque Therapeutics, Inc.
InventorsThomas Lars Andresen, Ditte Elisabeth Jaehger, Mie Linder Hubbe, Martin Kisha Kraemer
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Abstract
The present disclosure relates to specific delivery of a lipid-peptide conjugate to immune cells ex vivo or in vivo for decreasing or increasing an immune response against therapeutically relevant antigens. The lipid-peptide-antigen is comprised of a peptide, a lipid, and a functional group that is degraded in a biological environment within cells to release the peptide for MHC presentation and provides a more efficient presentation of antigen epitopes by antigen presenting cells than peptide epitopes alone.
Claims28
A lipid vehicle comprising at least one lipid-peptide conjugate,
- the lipid-peptide conjugate comprising a lipid moiety and a peptide moiety covalently conjugated by a linker,
- wherein the lipid moiety is selected from the group consisting of cholesterol, PEGylated phospholipid, and any combination thereof, and
- wherein the peptide moiety is an epitope of a therapeutically relevant antigen.
A lipid vehicle comprising at least one lipid-peptide conjugate and a liposome,
- the lipid-peptide conjugate comprising a lipid moiety and a peptide moiety covalently conjugated by a linker that comprises a disulfide bond,
- wherein the peptide moiety is an epitope of a therapeutically relevant antigen, and
- wherein the liposome has a diameter of about 50-900 nm.
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A method for preparing antigen-presenting cells (APCs), the method comprising:
- (a) contacting a population of monocytes, immature dendritic cells, and/or dendritic cells with a plurality of lipid vehicles in a medium under suitable conditions for the monocytes, immature dendritic cells, and/or dendritic cells to internalize one or more of the lipid vehicles, wherein each of the lipid vehicles comprises a plurality of lipid-peptide conjugates, each such conjugate comprising a lipid moiety and a peptide moiety covalently conjugated by a linker, and wherein each peptide moiety comprises a peptide fragment of an antigen;
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- (b) incubating the monocytes, immature dendritic cells, and/or dendritic cells in the presence of one or more cytokines and/or growth factors under suitable conditions to induce differentiation of the monocytes, maturation of the immature dendritic cells, and/or expansion of the dendritic cells, thereby to prepare a population of APCs.
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Dependencies are inferred from the claim text.