IP Library Granted Patent US 12,486,514
Granted Patent B2
US 12,486,514 · App. 17/267,617 · Granted Dec 2, 2025

Method to specifically stimulate survival and expansion of genetically-modified immune cells

Inventors: Natasha Vinanica (Singapore, SG); Arthur Yong (Singapore, SG); Dario Campana (Singapore, SG); Masaru Imamura (Niigata, JP)
Assignee: National University of Singapore
C12N15/625A61K40/11A61K40/31A61K40/4201A61K40/4211A61P35/02C07K14/7051C07K14/72C07K16/2803C12N5/0636C12N15/85A61K38/00A61K2239/31A61K2239/38A61K2239/48
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Quick Facts
Patent No.
US 12,486,514
App. No.
17/267,617
Granted
Dec 2, 2025
Kind
B2
Abstract

The present invention relates to a vector encoding a wildtype or truncated form of erythropoietin receptor (EpoR) to promote T cell survival and proliferation. Specifically, it exemplifies a bicistronic vector that expresses a truncated EpoR with an anti-CD19-41 BB-003ζ chimeric antigen receptor (CAR) that has a greater ex vivo expansion than CAR-T cells and demonstrates a significantly higher anti-leukemic activity in vivo. It also describes the method of producing cells expressing said vector and the use of these cells to kill CD19+ tumour cells.

Claims (30)

1 . A mammalian T cell comprising a vector, the vector comprising a nucleic acid encoding:

a) an erythropoietin (Epo) receptor;

b) a 2A peptide; and

c) a chimeric antigen receptor comprising:

i) a signal peptide;

ii an extracellular receptor domain that binds CD19;

iii) a hinge and transmembrane domain that anchors the extracellular receptor domain on the surface of a cell; and

iv) an effector domain;

wherein the Epo receptor is expressed on the mammalian T cell surface, and

wherein the nucleic acid encodes SEQ ID NO: 12.

2 . A method of making a transgenic mammalian T cell, the method comprising introducing a vector into a mammalian T cell, the vector comprising a nucleic acid encoding:

a) an erythropoietin (Epo) receptor;

b) a 2A peptide; and

c) a chimeric antigen receptor comprising:

i) a signal peptide;

ii) an extracellular receptor domain that binds CD19;

iii) a hinge and transmembrane domain that anchors the extracellular receptor domain on the surface of the mammalian T cell; and

iv) an effector domain;

wherein the Epo receptor is expressed on the mammalian T cell surface, and

wherein the nucleic acid encodes SEQ ID NO: 12.

3 . The method of claim 2 , wherein the mammalian T cell further expresses a T-cell receptor (TCR) that binds a tumor antigen or a viral antigen.

4 . The method of claim 3 , wherein the TCR is endogenous.

5 . The method of claim 4 , wherein the mammalian T cell is a tumor-infiltrating lymphocyte (TIL), and wherein the method further comprises extracting the tumor-infiltrating lymphocyte from a tumor and expanding the TIL ex vivo.

6 . The mammalian T cell of claim 1 , wherein the mammalian T cell is a human T cell.

7 . The mammalian T cell of claim 1 , wherein the mammalian T cell is a human peripheral blood T lymphocyte.

8 . The mammalian T cell of claim 1 , wherein the mammalian T cell expresses a T-cell receptor (TCR) that binds a tumor antigen or a viral antigen.

9 . The mammalian T cell of claim 8 , wherein the TCR is endogenous.

10 . The mammalian T cell of claim 9 , wherein the mammalian T cell is a tumor-infiltrating lymphocyte (TIL).

11 . The mammalian T cell of claim 1 , wherein the mammalian T cell is a CD8+ T cell.

12 . The method of claim 2 , wherein the mammalian T cell is a CD8+ T cell.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 10, 2021
From: VINANICA, NATASHA; YONG, ARTHUR; CAMPANA, DARIO; IMAMURA, MASARU
To: NATIONAL UNIVERSITY OF SINGAPORE
Reel/Frame 055216/0393 →
Continuity (2)
Provisional Application 62724488 · Aug 29, 2018
Related Publication 20210324388A1 · Oct 21, 2021
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