IP Library › Granted Patent US 12,485,102
Granted Patent B2
US 12,485,102 · App. 16/635,217 · Granted Dec 2, 2025

Methods and compositions for treating cancer

Inventors: Hildegund C. J. Ertl (Villanova, PA); Joseph M. Salvino (Chester Springs, PA); Valli V. S. Yellamelli (Philadelphia, PA)
Assignee: The Wistar Institute of Anatomy and Biology
A61K31/216A61K31/197A61K40/11A61K40/31A61K40/42A61K45/06A61K2239/31A61K2239/38A61K2239/57C07K16/2818
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Quick Facts
Patent No.
US 12,485,102
App. No.
16/635,217
Granted
Dec 2, 2025
Kind
B2
Abstract

Methods for treating cancer are disclosed which comprise administering to a subject T cells which have been pretreated ex vivo or in vitro with fenofibric acid (FFA), an FFA prodrug, or a derivative thereof that has PPAR-α agonist activity. These compounds promote the use of fatty acid catabolism rather than glucose for energy and promote enhanced recovery of, and biomass production by, the pre-treated T cells. Still other methods comprise co-administering to a subject having a cancer characterized by a solid tumor an immunotherapeutic composition targeting an antigen or ligand on the tumor cell and the pretreated T cells. The method may also employ co-administration of a checkpoint inhibitor. Novel compositions comprise the pre-treated T cells. Novel FFA prodrugs are provided.

Claims (14)

1 . A method for treating cancer comprising administering to a subject having a cancer a T cell or T cell population that is pretreated or conditioned ex vivo or in vitro with fenofibric acid (FFA), an FFA prodrug, or a derivative thereof that has PPAR-α agonist activity wherein the FFA prodrug is(S)-2-((S)-2-(2-(4-(4-chlorobenzoyl)phenoxy)-2-methyl propanamido)propanamido) pentanedioic acid (FFP or Compound 4) or(S)-2-((S)-2-(2-(2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoyloxy)acetamido)propanamido) pentanedioic acid (Compound 8).

2 . The method according to claim 1 , further comprising administering a checkpoint inhibitor in the form of an antibody or a small molecule.

3 . The method according to claim 2 , wherein the checkpoint inhibitor is an anti-PD-1 antibody or small molecule ligand.

4 . The method according to claim 1 , wherein the T cell is an autologous or heterologous, naturally occurring T cell or a recombinantly or synthetically modified T cell construct, or a human T cell or natural killer (NK) T cell or T infiltrating lymphocyte (TIL) obtained from the subject or from a bone marrow transplant match for the subject, or a T cell obtained from human peripheral blood or from the tumor microenvironment of the subject, or a T cell modified to express a heterologous antigen receptor, or a chimeric antigen receptor or a chimeric endocrine receptor prior to said pretreatment, or an endogenous or heterologous human T cell or human T cell line, or a CD8+ T cell.

5 . The method according to claim 1 , wherein the pretreated T cells are administered (a) once or repeatedly or (b) are administered in a single dose or as one or more doses or (c) are administered systemically by intravenous injection or infusion.

6 . The method according to claim 1 , wherein the cancer or tumor targeted by the method is characterized by hypoxia, significant infiltration with T lymphocytes, and low glucose in the tumor microenvironment.

7 . A composition comprising a T cell or T cell population that has been pretreated ex vivo or in vitro with fenofibric acid (FFA), a prodrug thereof, or a derivative thereof that has PPAR-α agonist activity.

8 . The composition according to claim 7 , wherein the prodrug is Compound 4 or Compound 8.

9 . The composition according to claim 7 , wherein said FFA, prodrug or derivative enhances cellular biomass production in activated T cells in vitro.

10 . The composition according to claim 7 , wherein the T cell is an autologous or heterologous, naturally occurring T cell or a recombinantly or synthetically modified T cell construct, or a human T cell or natural killer (NK) T cell or T infiltrating lymphocyte (TIL) obtained from the subject or from a bone marrow transplant match for the subject, or a T cell obtained from human peripheral blood or from the tumor microenvironment of the subject, or a T cell modified to express a heterologous antigen receptor, or a chimeric antigen receptor or a chimeric endocrine receptor prior to said pretreatment, or an endogenous or heterologous human T cell or human T cell line, or a CD8+ T cell, is a chimeric antigen receptor-T cell or a chimeric endocrine receptor-T cell or an ex vivo expanded tumor antigen-specific T cells that is pretreated before adoptive cell transfer to a subject having a solid tumor.

11 . A method of modifying a T cell comprising pretreating the T cell ex vivo or in vitro with fenofibric acid (FFA), an FFA prodrug, or a derivative thereof that has PPAR-α agonist activity.

12 . The composition according to claim 11 , wherein the prodrug is Compound 4 or Compound 8.

13 . The method according to claim 1 , wherein the cancer is melanoma.

14 . The method of claim 1 , wherein the FFA, FFA prodrug, or derivative thereof is FFA.

Continuity (2)
Provisional Application 62540338 · Aug 2, 2017
Related Publication 20210113613A1 · Apr 22, 2021
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