IP Library Granted Patent US 12,590,309
Granted Patent B2
US 12,590,309 · App. 17/613,130 · Granted Mar 31, 2026

Reprogramming of lipid metabolism to inhibit T cell senescence and enhance tumor immunotherapy

Inventors: Guangyong Peng (St. Louis, MO); Xia Liu (St. Louis, MO)
Assignee: Saint Louis University
C12N15/1137A61K31/7088A61K40/11A61K40/4271A61K40/4273A61P35/00C12N5/0637G01N33/5011G01N33/505G01N33/573A61K2239/31A61K2239/57G01N2333/916
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Quick Facts
Patent No.
US 12,590,309
App. No.
17/613,130
Granted
Mar 31, 2026
Kind
B2
Abstract

The present disclosure provides compositions and methods for inhibiting T cell senescence and improving T cell immunotherapies. In particular, inhibitors of group IV A phospholipase A2 are disclosed as useful in modulating the lipid metabolism of cells, in particular effector T cells, such that T reg- and tumor cell-induced cell senescence is abrogated. These methods may be employed with particular utility in adoptive T cell therapies and/or enhanced T cell effector functions in vivo, including those performed in combination with checkpoint blockade therapies.

Claims (15)

1 . A method of inhibiting induction of senescence in a cell comprising contacting said cell with an inhibitor of group IVA phosopholipase A 2 , wherein the inhibitor is not KU55933, and wherein:

(a) the cell is contacted ex vivo and administered to a subject; or

(b) the cell is located in a subject.

2 . The method of claim 1 , wherein said cell is a T cell.

3 . The method of claim 2 , wherein said T cell is a CD4+ T cell or a CD8+ T cell.

4 . The method of claim 1 , wherein said inhibitor of group IVA phosopholipase A 2 is contacted with said cell more than once.

5 . The method of claim 1 , wherein said cell is located in a subject.

6 . The method of claim 5 , wherein the inhibitor of group IVA phosopholipase A 2 is delivered systemically.

7 . The method of claim 5 , wherein the cell is located in a tumor microenvironment.

8 . The method of claim 7 , wherein the inhibitor or group IVA phosopholipase A 2 is delivered to the tumor microenvironment.

9 . The method of claim 1 , wherein said cell is contacted ex vivo and then administered to a subject.

10 . The method of claim 9 , wherein the cell was originally obtained from said subject prior to contacting with the inhibitor of group IVA phosopholipase A 2 .

11 . The method of claim 1 , wherein said inhibitor of group IVA phosopholipase A 2 is a pharmacologic inhibitor of group IVA phosopholipase A 2 .

12 . The method of claim 1 , wherein said inhibitor of group IVA phosopholipase A 2 is an inhibitory oligonucleotide.

13 . The method of claim 12 , wherein said inhibitory oligonucleotide is a ribozyme, an antisense oligonucleotide, an shRNA, an siRNA or a CRISPR-Cas9 gRNA.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jan 9, 2023
From: SAINT LOUIS UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 062320/0772 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 22, 2022
From: PENG, GUANGYONG; LIU, XIA
To: SAINT LOUIS UNIVERSITY
Reel/Frame 059336/0325 →
Continuity (2)
Provisional Application 62850258 · May 20, 2019
Related Publication 20220220482A1 · Jul 14, 2022
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