Apolipoprotein fusion proteins for cell-specific immune regulation
AssigneeBio-TRIP B.V.
InventorsRoy VAN DER MEEL, Willem J.M. MULDER, Maarten MERKX, David Pepijn SCHRIJVER, Anne DE DREU, Ayla Martine HOKKE, Koen DE BRUIN
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Abstract
The invention relates to fusion proteins of apolipoprotein with an immunomodulatory biomolecule and/or a rerouting molecule. The fusion proteins can be used as a carrier for an immunomodulatory biomolecule as such or incorporated in a lipid nanoparticle. The fusion protein finds use in the treatment of immune related disorders, or targeting a payload to a specific target site.
Claims62
An apolipoprotein lipid nanoparticle comprising
- a fusion protein comprising an apolipoprotein or an apolipoprotein mimetic and an immunomodulatory biomolecule;
- and
- phospholipids;
- wherein the immunomodulatory biomolecule is a protein that enhances or suppresses an immune response.
An apolipoprotein lipid nanoparticle comprising
- a fusion protein comprising an apolipoprotein or an apolipoprotein mimetic and a rerouting molecule;
- and
- phospholipids;
- wherein the rerouting molecule is a molecule that allows that fusion protein to bind to a different target than to which the apolipoprotein or apolipoprotein mimetic would have bound and/or to bind to its intended target with a higher affinity.
An apolipoprotein lipid nanoparticle comprising
- a fusion protein comprising an apolipoprotein or an apolipoprotein mimetic, an immunomodulatory biomolecule, and a rerouting molecule;
- and
- phospholipids;
- wherein the immunomodulatory biomolecule is a protein that enhances or suppresses an immune response;
- and
- wherein the rerouting molecule is a molecule that allows that fusion protein to bind to a different target than to which the apolipoprotein or apolipoprotein mimetic would have bound and/or to bind to its intended target with a higher affinity.
A fusion protein comprising an apolipoprotein or an apolipoprotein mimetic and an immunomodulatory biomolecule, wherein the immunomodulatory biomolecule is a protein that enhances or suppresses an immune response, for use in targeting said immunomodulatory biomolecule to a myeloid cell.
A fusion protein comprising an apolipoprotein or an apolipoprotein mimetic and a rerouting molecule, wherein the rerouting molecule is a molecule that allows that fusion protein to bind to a different target than to which the apolipoprotein or apolipoprotein mimetic would have bound and/or to bind to its intended target with a higher affinity.
A fusion protein comprising an apolipoprotein or an apolipoprotein mimetic and interleukin-4 (IL-4).
A fusion protein comprising a myeloid-targeting molecule and IL-4, wherein the myeloid-targeting molecule is capable of targeting the IL-4 to a myeloid cell.
A nucleic acid comprising a nucleic acid sequence at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO. 44 or comprising a nucleic acid sequence encoding a polypeptide having a sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO. 43 and further comprising means for targeted expression in a myeloid cell, wherein said mean are selected from:
- a promoter for selective or inducible expression in said myeloid cell operatively linked to said nucleic acid;
- or
- a viral expression vector comprising said nucleic acid capable of stably expressing said nucleic acid in said myeloid cell;
- or
- a lipid nanoparticle comprising one or more apolipoproteins, phospholipids, said nucleic acid, and optionally sterol.
In vivo, in vitro or ex vivo use of IL-4 in stimulating or promoting trained immunity in a cell, organ, tissue or an organism.
Dependencies are inferred from the claim text.