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US 2026/0209309 A1Published application
Methods for macrophage polarization
AssigneeUniversitäT ZüRich
InventorsSimon BREDL, Roberto SPECK
Life of this patent
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Abstract
The present invention relates to a chimeric cytokine receptor and its use in switching the polarisation of macrophages or monocytes from M2 to M1. The present invention also relates to a method for monocyte modification to selectively increase the phagocytotic activity and to modulate the polarisation of offspring macrophages.
Claims23
An isolated monocyte or macrophage comprising a chimeric cytokine receptor (ChCR) polypeptide heterodimer comprising or consisting of a first ChCR polypeptide and a second ChCR polypeptide;
- wherein the first ChCR polypeptide comprises:
- a first extracellular domain,
- a first type 1 transmembrane domain,
- optionally, a first flexible linker domain, linking said first extracellular domain and said first transmembrane domain,
- a first intracellular domain,
- and wherein the second ChCR polypeptide comprises:
- a second extracellular domain,
- a second type 1 transmembrane domain,
- optionally, a second flexible linker domain, linking said second extracellular domain and said second transmembrane domain,
- a second intracellular domain,
- wherein
- the first extracellular domain and the second extracellular domain are able to induce dimerization of said ChCR polypeptide heterodimer upon binding to a cytokine selected from IL-10 and TGFβ;
- and
- the first intracellular domain and the second intracellular domain are able to activate IFNγ receptor/Jak1/Jak2/STAT1 signalling in monocytes and/or macrophages upon dimerization of said ChCR polypeptide heterodimer.
11 more elements
The isolated monocyte or macrophage according to any one of the preceding claims, wherein the monocyte or macrophage additionally comprises an inhibitory nucleic acid molecule directed against SIRβα.
The isolated monocyte or macrophage according to any one of claims, wherein the monocyte or macrophage additionally comprises a chimeric antigen receptor (CAR) polypeptide, comprising:
- an extracellular antigen binding domain, in particular a Fab-fragment,
- a transmembrane domain, in particular a CD8 transmembrane domain, and
- an intracellular domain comprising at least one ITAM motif, in particular the intracellular domain of a FC-receptor, more particular the intracellular domain of a FCgamma-receptor or of CD32a,
- optionally, a linker domain, linking said extracellular antigen binding domain and said transmembrane domain.
1 more element
An isolated monocyte or macrophage according to any one of the preceding claims for use in treatment or prevention of cancer.
A ChCR polypeptide heterodimer comprising:
- a first extracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 21,
- a first transmembrane domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 26, and
- a first intracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 28;
- a second extracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 22,
- a second transmembrane domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 27, and
- a second intracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 29.
3 more elements
A ChCR polypeptide heterodimer comprising:
- a first extracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 21,
- a first transmembrane domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 27, and
- a first intracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 29;
- a second extracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 22,
- a second transmembrane domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 26, and
- a second intracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 28.
3 more elements
A ChCR polypeptide heterodimer comprising:
- a first extracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 23,
- a first transmembrane domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 26, and
- a first intracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 28;
- a second extracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 24,
- a second transmembrane domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 27, and
- a second intracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 29.
3 more elements
A ChCR polypeptide heterodimer comprising:
- a first extracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 23,
- a first transmembrane domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 27, and
- a first intracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 29;
- a second extracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 24,
- a second transmembrane domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 26, and
- a second intracellular domain comprising a sequence having at least ≥80%, ≥85%, ≥90%, ≥92%, ≥94%, ≥95%, ≥96%, ≥97%, ≥98%, ≥99%, or 100% identity to SEQ ID NO 28.
3 more elements
Dependencies are inferred from the claim text.