US 12,239,693 B2
Use of lentivector-transduced T-Rapa cells for amelioration of lysosomal storage disorders
Jeffrey A. Medin, Shorewood, WI (US); Daniel H. Fowler, Milwaukee, WI (US); Murtaza S. Nagree, Milwaukee, WI (US); and Tania Felizardo, Milwaukee, WI (US)
Assigned to The Medical College of Wisconsin, Inc., Milwaukee, WI (US)
Appl. No. 17/050,949
Filed by The Medical College of Wisconsin, Inc., Milwaukee, WI (US)
PCT Filed Apr. 29, 2019, PCT No. PCT/US2019/029639
§ 371(c)(1), (2) Date Oct. 27, 2020,
PCT Pub. No. WO2019/210301, PCT Pub. Date Oct. 31, 2019.
Claims priority of provisional application 62/663,786, filed on Apr. 27, 2018.
Prior Publication US 2021/0322472 A1, Oct. 21, 2021
Int. Cl. C12N 15/86 (2006.01); A61K 35/17 (2015.01); A61K 38/44 (2006.01); A61K 38/47 (2006.01); A61K 39/00 (2006.01); A61P 43/00 (2006.01); C12N 5/0783 (2010.01); C12N 15/63 (2006.01); C12N 15/79 (2006.01)
CPC A61K 38/443 (2013.01) [A61K 38/47 (2013.01); A61K 39/4611 (2023.05); A61K 39/464 (2023.05); A61P 43/00 (2018.01); C12N 5/0636 (2013.01); C12N 15/86 (2013.01); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); C12N 15/79 (2013.01); C12N 2510/00 (2013.01); C12Y 101/01205 (2013.01); C12Y 302/01022 (2013.01)] 12 Claims
 
1. A method comprising:
(a) conditioning T-cells from a subject with rapamycin ex vivo to generate T-Rapa cells, wherein the subject is suffering from Fabry disease;
(b) transducing the T-Rapa cells in vitro with a vector comprising a transgene of interest that encodes an enzyme associated with a lysosomal storage disorder, wherein the enzyme associated with the lysosomal storage disorder is a-galactosidase A (α-gal A);
(c) expanding the vector-transduced T-Rapa cells by culturing in vitro; and
(d) administering the expanded transduced T-Rapa cells of step (c) derived from the subject to the subject by intravenous infusion, wherein the T-Rapa cells express the enzyme associated with the lysosomal storage disorder in the subject and reduce a level of globotriaosylceramide (Gb3) in the subject.