T cells with reduced surface fucosylation and methods of making and using the same

Patent metadata

Field	Value
Publication number	US-11891644-B2
Application number	US-201816616928-A
Country	US
Kind code	B2
Filing date	Jun 5, 2018
Priority date	Jun 7, 2017
Publication date	Feb 6, 2024
Grant date	Feb 6, 2024

Abstract

Methods of producing T cells having reduced surface fucosylation and use thereof in adoptive cell therapy, in particular, in cancer treatment are provided.

First claim

What is claimed is:

1. A method of producing T cells having reduced surface fucosylation, the method comprising:
culturing T cells in the presence of an effective amount of a fucose analog in a cell culture medium; wherein

said fucose analog is selected from the group consisting of formulae (I) and (II):

or a pharmaceutically acceptable salt or solvate form thereof, wherein each of formula (I) or (II) can be the alpha or beta anomer or the corresponding aldose form;
R 2 is halogen; each of R 1 , R 3 , and R 4 is independently —OH or a hydrolyzable ester group; and R 5 is —CH 3 , or
each of R 1 , R 2 , R 3 , and R 4 is independently —OH or a hydrolyzable ester group; and R 5 is —C≡CH;
and

wherein said T cells cultured in the presence of the effective amount of said fucose analog have at least about 80% reduced surface fucosylation relative to T cells cultured in the absence of said fucose analog; and wherein the T cells having reduced surface fucosylation are configured to be used in an adoptive cell therapy.

2. The method of claim 1 , further comprising a step of isolating the T cells having reduced surface fucosylation.

3. The method of claim 1 , wherein the fucose analog is 2-deoxy-2-fluoro-L-fucose.

4. The method of claim 1 , wherein the fucose analog is alkynyl fucose peracetate.

5. The method of claim 1 , wherein said T cells comprise human peripheral T cells.

6. The method of claim 1 , wherein said T cells having reduced surface fucosylation are T cells having at least about 85% reduction of surface fucosylation relative to T cells cultured in the absence of said fucose analog.

7. The method of claim 1 , wherein said T cells having reduced surface fucosylation are T cells having at least about 90% reduction of surface fucosylation relative to T cells cultured in the absence of said fucose analog.

8. The method of claim 1 , wherein said T cells having reduced surface fucosylation are T cells having at least about 95% reduction of surface fucosylation relative to T cells cultured in the absence of said fucose analog.

Assignees

• Seagen Inc

Inventors

• Okeley Nicole
• Field Jessica
• Gardai Shyra
• Heiser Ryan

Classifications

• C12N2501/51

  B7 molecules, e.g. CD80, CD86, CD28 (ligand), CD152 (ligand) · CPC title

• C12N2501/515

  CD3, T-cell receptor complex · CPC title

• C12N2501/2302

  Interleukin-2 (IL-2) · CPC title

• C12N2500/34

  Sugars · CPC title

• A61K40/42

  Cancer antigens · CPC title