T cells with reduced surface fucosylation and methods of making and using the same
Methods of producing T cells having reduced surface fucosylation and use thereof in adoptive cell therapy, in particular, in cancer treatment are provided.
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.