Artificial receptor having shedding structure

Patent metadata

Field	Value
Publication number	US-2025361285-A1
Application number	US-202318998362-A
Country	US
Kind code	A1
Filing date	Jul 14, 2023
Priority date	Jul 26, 2022
Publication date	Nov 27, 2025
Grant date	—

Abstract

The present invention provides: an artificial receptor including a ligand-binding site, a transmembrane domain having a shedding structure, and a signal transduction domain into an immune cell; and a nucleic acid encoding the artificial receptor.

First claim

1 . An artificial receptor, comprising a ligand-binding site, a transmembrane domain having a shedding structure, and a signal transduction domain into an immune cell.

2 . The artificial receptor according to claim 1 , which is selected from the group consisting of a chimeric antigen receptor, a modified T cell receptor, a modified Fc receptor, and a modified tyrosine kinase receptor.

3 . The artificial receptor according to claim 1 , wherein the immune cell is selected from the group consisting of a T cell, a natural killer cell, and a macrophage.

4 . The artificial receptor according to claim 3 , wherein the T cell is a cytotoxic T cell.

5 . The artificial receptor according to claim 1 , wherein the shedding structure is derived from a protein selected from the group consisting of a notch protein, an amyloid precursor protein, and CD28.

6 . The artificial receptor according to claim 1 , wherein the signal transduction domain into an immune cell comprises a signal transduction domain derived from at least one type selected from the group consisting of a CD3ζ chain, CD28, and 4-1BB.

7 . The artificial receptor according to claim 1 , wherein the transmembrane domain having a shedding structure comprises
(1) an amino acid sequence represented by SEQ ID NO: 26, or (2) an amino acid sequence obtained by substituting, deleting, inserting, and/or adding one or several amino acids in the amino acid sequence of (1).

8 . The artificial receptor according to claim 1 , having no γ-secretase cleavage site in the transmembrane domain.

9 . The artificial receptor according to claim 1 , comprising two or more identical signal transduction domains.

10 . A nucleic acid encoding the artificial receptor according to claim 1 .

11 . An immune cell comprising the artificial receptor according claim 1 .

12 . A medicine comprising the immune cell according to claim 11 .

13 . A method for designing a receptor with regulated trogocytosis effect or a nucleic acid encoding the receptor, comprising
(1) a step of selecting a receptor comprising a ligand-binding site, a transmembrane domain, and a signal transduction domain into an immune cell, and (2A) a step of adjusting sensitivity of the transmembrane domain of the receptor selected in the step (1) to shedding, and/or (2B) a step of adding, inserting, and/or deleting one or more amino acid residues in the signal transduction domain of the receptor prepared selected in the step (1), and/or substituting one or more amino acid residues in the signal transduction domain.

14 . A method for producing a receptor with regulated trogocytosis effect or a nucleic acid encoding the receptor, comprising
(1) a step of preparing a receptor that includes a ligand-binding site, a transmembrane domain, and a signal transduction domain into an immune cell, and (2A) a step of adjusting sensitivity of the transmembrane domain of the receptor prepared in the step (1) to shedding, and/or (2B) a step of adding, inserting, and/or deleting one or more amino acid residues in the signal transduction domain of the receptor prepared in the step (1), and/or substituting one or more amino acid residues in the signal transduction domain.

15 . The method according to claim 13 , wherein the receptor selected in the step (1) is selected from the group consisting of a chimeric antigen receptor, a T cell receptor, an Fc receptor, and a tyrosine kinase receptor.

16 . An immune cell comprising the nucleic acid according to claim 10 .

17 . The method according to claim 14 , wherein the receptor prepared in the step (1) is selected from the group consisting of a chimeric antigen receptor, a T cell receptor, an Fc receptor, and a tyrosine kinase receptor.

Assignees

• Univ Kyoto

Inventors

• Kaneko Shin
• Minagawa Atsutaka

Classifications

• C12N2510/00

  Genetically modified cells · CPC title

• C12N15/11

  DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity} · CPC title

• C12N5/10

  Cells modified by introduction of foreign genetic material · CPC title

• C12N5/0634

  Cells from the blood or the immune system · CPC title

• C07K2319/03

  containing a transmembrane segment · CPC title