Granted Patent
B2
US 12,655,425 · App. 17/312,361 · Granted Jun 16, 2026
Nrf-2 deficient cells and uses thereof
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Abstract
The present disclosure relates to T cell anticancer immunotherapy based on modulation of Nrf2 expression, that is, to an Nrf2-targeting immune cell, e.g., T cell, anticancer therapy. The present disclosure allows deep interference with the Nrf2 expression in T cells, thereby solving the problem of immune tolerance shown by cancer cells to T cells; in other words, the effect of anticancer immunotherapy can be improved by targeting Nrf2. The present disclosure can provide an Nrf2-targeting new T cell anticancer immunotherapy and a T cell for the second-generation anticancer immunotherapy. This technology is applicable to the preparation of CAR-T, engineered T, and TIL T cells, and to the treatment of various solid carcinomas, including lymphoma. It can be said to be a new anticancer therapy that improves the therapeutic efficacy effectively.
Claims (12)
1 . A method of treating a tumor in a subject in need thereof, comprising administering to the subject a modified cell which expresses a reduced expression level of a NFE2L2 gene and/or a protein encoded thereof, compared to a corresponding non-modified cell, wherein the modified cell comprises a chimeric antigen receptor (CAR) and/or a T cell receptor (TCR).
2 . The method of claim 1 , wherein the expression level of the NFE2L2 gene and/or protein encoded thereof is reduced by at least about 50%, compared to the corresponding non-modified cell.
3 . The method of claim 1 , wherein after the administration: (i) a tumor volume in the subject is reduced, (ii) a tumor weight in the subject is reduced, (iii) one or more properties of a tumor-infiltrating lymphocyte (TIL) in the subject is improved, or (iv) any combination of (i)-(iii).
4 . The method of claim 1 , wherein the modified cell exhibits increased resistance to oxidative stress compared to the corresponding non-modified cell.
5 . The method of claim 1 , wherein the modified cell comprises a T cell, tumor-infiltrating lymphocyte (TIL), lymphokine-activated killer cell, natural killer (NK) cell, or any combination thereof.
6 . The method of claim 5 , wherein the T cell is a CD8+ T cell, CD4+ T cell, NKT cell, or a combination thereof.
7 . A method of preparing an immune cell for chimeric antigen receptor (CAR) and/or T cell receptor (TCR) engineering comprising contacting the immune cell with a gene editing tool which is capable of reducing an expression level of a NFE2L2 gene and/or protein encoded thereof, and, further comprising modifying the immune cell to express a CAR and/or a TCR.
8 . The method of claim 7 , wherein, after the contacting, the expression level of the NFE2L2 gene and/or protein encoded thereof is reduced by at least about 50%, compared to a corresponding immune cell that was not contacted with the gene editing tool.
9 . The method of claim 7 , wherein the immune cell comprises a T cell, tumor-infiltrating lymphocyte (TIL), lymphokine-activated killer cell, natural killer (NK) cell, or any combination thereof.
10 . The method of claim 7 , wherein the gene editing tool comprises a shRNA, siRNA, miRNA, antisense oligonucleotides, CRISPR, zinc finger nuclease, TALEN, meganuclease, restriction endonuclease, or any combination thereof.
11 . A CAR and/or TCR-expressing immune cell prepared by the method of claim 7 .
12 . A pharmaceutical composition comprising the CAR and/or TCR-expressing immune cell of claim 11 .
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 23, 2025
From: NEOIMMUNETECH, INC.
To: PUSAN NATIONAL UNIVERSITY INDUSTRY-UNIVERSITY COOPERATION FOUNDATION
Reel/Frame 071208/0806 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 16, 2023
From: HONG, CHANGWAN; LEE, BYUNG HA; CHOI, DONGHOON
To: NEOIMMUNETECH, INC.
Reel/Frame 063653/0445 →
Priority Claims (1)
KR 10-2018-0158428
· Dec 10, 2018
· national
Continuity (1)
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