US 11,891,644 B2
T cells with reduced surface fucosylation and methods of making and using the same
Nicole Okeley, Bothell, WA (US); Jessica Field, Bothell, WA (US); Shyra Gardai, Bothell, WA (US); and Ryan Heiser, Lake Stevens, WA (US)
Assigned to Seagen Inc., Bothell, WA (US)
Appl. No. 16/616,928
Filed by Seagen Inc., Bothell, WA (US)
PCT Filed Jun. 5, 2018, PCT No. PCT/US2018/036067
§ 371(c)(1), (2) Date Nov. 25, 2019,
PCT Pub. No. WO2018/226701, PCT Pub. Date Dec. 13, 2018.
Claims priority of provisional application 62/516,536, filed on Jun. 7, 2017.
Prior Publication US 2020/0149082 A1, May 14, 2020
Int. Cl. C12P 21/00 (2006.01); A61P 35/02 (2006.01); A61K 31/7024 (2006.01); A61K 35/17 (2015.01); C12N 5/0783 (2010.01); A61K 31/70 (2006.01)
CPC C12P 21/005 (2013.01) [A61K 31/70 (2013.01); A61K 31/7024 (2013.01); A61K 35/17 (2013.01); A61P 35/02 (2018.01); C12N 5/0636 (2013.01); C12N 2500/34 (2013.01)] 8 Claims
 
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):

OG Complex Work Unit Chemistry
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;
R2 is halogen; each of R1, R3, and R4 is independently —OH or a hydrolyzable ester group; and R5 is —CH3, or
each of R1, R2, R3, and R4 is independently —OH or a hydrolyzable ester group; and R5 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.