Method for producing gamma delta T cells

Patent metadata

Field	Value
Publication number	US-12391739-B2
Application number	US-201917259736-A
Country	US
Kind code	B2
Filing date	Jul 12, 2019
Priority date	Jul 13, 2018
Publication date	Aug 19, 2025
Grant date	Aug 19, 2025

Abstract

The present invention provides a method for producing a γδT cell from an induced pluripotent stem cell, wherein the induced pluripotent stem cell is derived from a cell other than an αβT cell.

First claim

The invention claimed is:

1. A method for producing a γδT cell from an induced pluripotent stem cell, wherein the induced pluripotent stem cell is derived from a cell other than an αβT cell, wherein the method comprises:
(1) establishing an induced pluripotent stem cell from a cell other than an αβT cell,
(2-1) differentiating the induced pluripotent stem cell established in (1) into a hematopoietic progenitor cell,
(2-2) differentiating the hematopoietic progenitor cell obtained from (2-1) into a T cell without using feeder cells, and
(3) introducing into any one of the (i) induced pluripotent stem cell obtained from step (1), (ii) a hematopoietic progenitor cell obtained from step (2-1) and (iii) a T cell obtained from step (2-2):
(a) a nucleic acid encoding a γTCR, and
(b) a nucleic acid encoding a δTCR.

2. The method according to claim 1 , wherein the cell other than an αβT cell is a mononuclear cell other than an αβT cell.

3. The method according claim 1 , wherein the cell other than an αβT cell is a monocyte.

4. The method according to claim 1 , the method further comprising a introducing into the (i) induced pluripotent stem cell obtained from step (1), (ii) a cell obtained during step (2-1) or step (2-2); and/or (iii) the induced pluripotent stem cell obtained from step (1) comprising the nucleic acid encoding a γTCR and the nucleic acid encoding the δTCR, or a cell obtained during step (2-1) or step (2-2) comprising the nucleic acid encoding a γTCR and the nucleic acid encoding the δTCR,
a nucleic acid encoding a CAR, which recognizes, and binds to a tumor-specific antigen or a tumor-associated antigen.

5. The method according to claim 1 , wherein the γTCR is Vγ9TCR and the δTCR is Vδ2TCR.

6. The method according to claim 1 , the method further comprising a introducing a nucleic acid encoding a fusion protein comprising IL-15 and IL-15Rα into the (i) induced pluripotent stem cell obtained from step (1), (ii) a cell obtained during step (2-1) or step (2-2); and/or (iii) the induced pluripotent stem cell obtained from step (1) comprising the nucleic acid encoding a γTCR and the nucleic acid encoding the δTCR, or the T cell obtained in step (2-1) or step (2-2) comprising the nucleic acid encoding the γTCR and the nucleic acid encoding the δTCR.

7. A γδT cell produced by the method according to claim 1 .

8. The method according to claim 1 , wherein the cell obtained during step (2-2) is an iPSC-derived T cell; or
wherein the cell obtained during step (2-1) is an iPSC-derived hematopoietic progenitor cell.

9. The method according to claim 4 , wherein the cell obtained during step (2-2) is an iPSC-derived T cell; or
wherein the cell obtained during step (2-1) is an iPSC-derived hematopoietic progenitor cell.

10. The method according to claim 6 , wherein the cell obtained during step (2-2) is an iPSC-derived T cell; or
wherein the cell obtained during step (2-1) is an iPSC-derived hematopoietic progenitor cell.

Assignees

• Univ Kyoto
• Takeda Pharmaceuticals Co

Inventors

• Kaneko Shin
• Iriguchi Shoichi
• Ueda Tatsuki
• Kassai Yoshiaki
• Hayashi Akira
• Nakayama Kazuhide

Classifications

• A61K40/4211

  CD19 or B4 · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/48

  Blood cells, e.g. leukemia or lymphoma · CPC title

• C12N5/0636 Primary

  T lymphocytes · CPC title