Method of selecting t cells with improved anti-cancer activity

Patent metadata

Field	Value
Publication number	US-2024003870-A1
Application number	US-202118251751-A
Country	US
Kind code	A1
Filing date	Nov 5, 2021
Priority date	Nov 5, 2020
Publication date	Jan 4, 2024
Grant date	—

Abstract

A method of selecting T cells with improved anti-cancer activity, the method including: a) quantifying glucose transporter 1 (GLUT1) expression level at the cell surface of a population of T cells by using a GLUT1 ligand, b) selecting T cells having a low GLUT1 expression level, wherein the T cells having a low GLUT1 expression level have improved anti-cancer activity. Also, a population of T cells with improved anti-cancer activity for use in the treatment of cancer, to the use of a GLUT1 ligand for selecting T cells with improved anti-cancer activity, and to the use of GLUT1 as a biomarker of the anti-cancer therapeutic efficacy of T cells.

First claim

1 - 15 . (canceled)

16 . A method of selecting T cells with improved anti-cancer activity, said method comprising:
a) quantifying glucose transporter 1 (GLUT1) expression level at the cell surface of a population of T cells by using a GLUT1 ligand, b) selecting T cells having a low GLUT1 expression level, wherein said T cells having a low GLUT1 expression level have improved anti-cancer activity.

17 . The method according to claim 16 , comprising:
a0) contacting a population of T cells expressing GLUT1 at their cell surface, or susceptible to express GLUT1 at their cell surface, with a GLUT1 ligand, a1) detecting and/or quantifying the binding of said GLUT1 ligand to GLUT1 at the cell surface of the T cells, a2) quantifying GLUT1 expression level at the cell surface of the T cells, b) selecting T cells having a low GLUT1 expression level, and c) optionally, isolating the selected T cells having a low GLUT1 expression level.

18 . The method according to claim 16 , wherein said T cells having a low GLUT1 expression level corresponds to the at most 50%, 40%, 30%, 20%, 10% or 5% fraction with the lowest GLUT1 expression level among the total GLUT1+T cell population.

19 . The method according to claim 16 , wherein quantifying GLUT1 expression level at the cell surface of the T cells is done by flow cytometry.

20 . A method of treating cancer in a subject in need thereof, said method comprising:
selecting T cells with improved anti-cancer activity by the method according to claim 16 , and administering to the subject a therapeutic amount of said T cells with improved anti-cancer activity.

21 . A method of selecting T cells with improved anti-cancer activity comprising contacting T cells with a glucose transporter 1 (GLUT1) ligand for selecting T cells with improved anti-cancer activity.

22 . The method according to claim 16 , wherein said GLUT1 ligand is labeled.

23 . The method according to claim 16 , wherein said GLUT1 ligand comprises a receptor binding domain (RBD) derived from the soluble part of an envelope glycoprotein of a primate T-lymphotropic virus (PTLV), or comprises an antibody or an antigen-binding fragment thereof.

24 . The method according to claim 16 , wherein said GLUT1 ligand comprises a receptor binding domain (RBD) derived from the soluble part of an envelope glycoprotein of human T-cell leukemia virus type 1 (HTLV-1), human T-cell leukemia virus type 2 (HTLV-2), human T-cell leukemia virus type 3 (HTLV-3), human T-cell leukemia virus type 4 (HTLV-4), simian T-cell leukemia virus type 1 (STLV-1), simian T-cell leukemia virus type 2 (STLV-2), simian T-cell leukemia virus type 3 (STLV-3), or simian T-cell leukemia virus type 5 (STLV-5).

25 . The method according to claim 16 , wherein said GLUT1 ligand comprises a receptor binding domain (RBD) derived from the soluble part of an envelope glycoprotein of human T-cell leukemia virus type 2 (HTLV-2).

26 . The method according to claim 16 , wherein said receptor binding domain (RBD) comprises or consists of the amino acid sequence SEQ ID NO: 15.

27 . A method of determining an anti-cancer therapeutic efficacy of T cells, comprising monitoring glucose transporter 1 (GLUT1) as a biomarker of anti-cancer therapeutic efficacy of T cells.

28 . The method according to claim 16 , wherein said T cells are selected from the group consisting of conventional CD4 + T cells, conventional CD8 + T cells, γδ T cells and double negative (DN) T cells.

29 . The method according to claim 16 , wherein said T cells are chimeric antigen receptor (CAR) T cells.

30 . The method according to claim 16 , wherein said cancer is a blood cancer or a solid tumor.

31 . The method according to claim 20 , wherein said GLUT1 ligand comprises a receptor binding domain (RBD) derived from the soluble part of an envelope glycoprotein of human T-cell leukemia virus type 1 (HTLV-1), human T-cell leukemia virus type 2 (HTLV-2), human T-cell leukemia virus type 3 (HTLV-3), human T-cell leukemia virus type 4 (HTLV-4), simian T-cell leukemia virus type 1 (STLV-1), simian T-cell leukemia virus type 2 (STLV-2), simian T-cell leukemia virus type 3 (STLV-3), or simian T-cell leukemia virus type 5 (STLV-5).

32 . The method according to claim 20 , wherein said receptor binding domain (RBD) comprises or consists of the amino acid sequence SEQ ID NO: 15.

33 . The method according to claim 20 , wherein said T cells are selected from the group consisting of conventional CD4 + T cells, conventional CD8 + T cells, γδ T cells and double negative (DN) T cells.

34 . The method according to claim 20 , wherein said T cells are chimeric antigen receptor (CAR) T cells.

35 . The method according to claim 20 , wherein said cancer is a blood cancer or a solid tumor.

Assignees

• Metafora Biosystems
• Centre Nat Rech Scient
• Univ Montpellier
• The United States Of America Asrepresented By The Sec Dep Of Health And Human Service

Inventors

• Taylor Naomi
• Pouzolles Marie Charlotte Chantal
• Dardalhon Valérie
• Petit Vincent

Classifications

• A61K40/4211

  CD19 or B4 · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/48

  Blood cells, e.g. leukemia or lymphoma · CPC title

• A61K2239/38

  characterised by the dose, timing or administration schedule · CPC title