US 12,344,656 B2
Genetically engineered T cells having improved persistence in culture
Jonathan Alexander Terrett, Cambridge, MA (US); Demetrios Kalaitzidis, Cambridge, MA (US); and Hanspeter Waldner, Cambridge, MA (US)
Assigned to CRISPR Therapeutics AG, Zug (CH)
Filed by CRISPR Therapeutics AG, Zug (CH)
Filed on Sep. 4, 2020, as Appl. No. 17/012,957.
Claims priority of provisional application 63/034,646, filed on Jun. 4, 2020.
Claims priority of provisional application 62/927,764, filed on Oct. 30, 2019.
Claims priority of provisional application 62/897,016, filed on Sep. 6, 2019.
Prior Publication US 2021/0079347 A1, Mar. 18, 2021
Int. Cl. C07K 14/705 (2006.01); A61K 31/7105 (2006.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/42 (2025.01); A61K 40/50 (2025.01); C12N 5/0783 (2010.01); C12N 9/22 (2006.01); C12N 15/113 (2010.01)
CPC C07K 14/70596 (2013.01) [A61K 31/7105 (2013.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/4202 (2025.01); A61K 40/4211 (2025.01); A61K 40/4215 (2025.01); C12N 5/0636 (2013.01); C12N 9/22 (2013.01); C12N 15/113 (2013.01); A61K 40/50 (2025.01); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/48 (2023.05); C12N 2310/20 (2017.05); C12N 2510/00 (2013.01)] 13 Claims
 
1. A population of genetically engineered T cells, comprising:
(i) a disrupted Ten-Eleven Translocation-2 (TET2) gene;
(ii) a disrupted T cell receptor alpha chain constant region (TRAC) gene;
(iii) a disrupted beta-2-microglobulin (β2M) gene;
(iv) a disrupted CD70 gene; and
(v) a disrupted FAS Cell Surface Death Receptor (FAS) gene;
wherein the population of genetically engineered T cells, as compared to non-engineered T cell counterparts, have the following features: (a) enhanced expansion capacity in culture, (b) enhanced proliferation capacity in vivo, (c) a reduced apoptosis level in vivo, and (d) an enhanced frequency of activation.