IP Library › Granted Patent US 12,473,533
Granted Patent B2
US 12,473,533 · App. 17/259,085 · Granted Nov 18, 2025

Gene targets for T-cell-based immunotherapy

Inventors: Alexander Marson (Oakland, CA); Eric Shifrut (Oakland, CA); Julia Carnevale (Oakland, CA); Alan Ashworth (Oakland, CA)
Assignee: The Regents of the University of California
C12N5/0636A61K40/11A61K40/32A61K40/4269C12N9/22C12N15/111C12N15/113A61K2239/31A61K2239/38A61K2239/57C12N2310/11C12N2310/141C12N2310/20C12N2310/531C12N2320/34C12N2510/00
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Quick Facts
Patent No.
US 12,473,533
App. No.
17/259,085
Granted
Nov 18, 2025
Kind
B2
Abstract

Provided herein are genetically modified T cells that exhibit increased proliferation compared to wild-type T cells when stimulated, methods of generating such T cells, and methods of using the T cells for the treatment of a disease such as cancer.

Claims (10)

1 . A genetically modified hematopoietic cell that comprises a genetic modification that inhibits expression or activity of a polypeptide product encoded by a RAS p21 protein activator 2 (RASA2) gene, wherein expression or activity of the polypeptide product is inhibited by at least 60% compared to a control wild-type hematopoietic cell; wherein the genetically modified hematopoietic cell is a T-cell and inhibition of expression increases proliferation-of the cell induced by T-cell receptor signaling.

2 . The genetically modified hematopoietic cell of claim 1 , wherein the genetic modification inactivates the RASA2 gene.

3 . The genetically modified hematopoietic cell of claim 1 , wherein the genetically modified hematopoietic cell is a primary T-cell.

4 . The genetically modified hematopoietic cell of claim claim 1 , wherein the T-cell is a CD8+ T cell or CD4+ T cell.

5 . The genetically modified hematopoietic cell of claim 1 , wherein the RASA2 gene is inhibited using a clustered, regularly interspaced, short palindromic repeats (CRISPR) system.

6 . The genetically modified hematopoietic cell of claim 1 , wherein the RASA2 gene is inhibited using a transcription activator-like effector nuclease (TALEN) system, a zinc finger nuclease system, or a meganuclease system.

7 . The genetically modified hematopoietic cell of claim 1 , wherein the RASA2 gene is inhibited using inhibitory RNA.

8 . The genetically modified hematopoietic cell of claim 1 , wherein the RASA2 gene is inhibited using shRNA, siRNA, microRNA, or an antisense RNA.

9 . A population of cells comprising the genetically modified cell of claim 1 .

10 . A cell culture comprising a genetically modified hematopoietic cell of claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 10, 2022
From: MARSON, ALEXANDER; SHIFRUT, ERIC; CARNEVALE, JULIA; ASHWORTH, ALAN
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 059230/0868 →
Continuity (2)
Provisional Application 62695672 · Jul 9, 2018
Related Publication 20210317406A1 · Oct 14, 2021
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