US 12,187,780 B2
Car t-cells comprising inactivated CBL and CBL-B genes
Hamid Band, Omaha, NE (US); Vimla Band, Omaha, NE (US); Fany Iseka, Omaha, NE (US); Bhopal Mohapatra, Omaha, NE (US); and Matthew Storck, Omaha, NE (US)
Assigned to BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA, Lincoln, NE (US)
Appl. No. 16/484,504
Filed by BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA, Lincoln, NE (US)
PCT Filed Feb. 23, 2018, PCT No. PCT/US2018/019408
§ 371(c)(1), (2) Date Aug. 8, 2019,
PCT Pub. No. WO2018/156886, PCT Pub. Date Aug. 30, 2018.
Claims priority of provisional application 62/473,802, filed on Mar. 20, 2017.
Claims priority of provisional application 62/462,641, filed on Feb. 23, 2017.
Prior Publication US 2019/0374578 A1, Dec. 12, 2019
Int. Cl. A61K 35/17 (2015.01); A61K 39/00 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01); C07K 16/32 (2006.01); C12N 5/0783 (2010.01); C12N 15/113 (2010.01)
CPC C07K 14/70521 (2013.01) [A61K 39/4611 (2023.05); A61K 39/4631 (2023.05); A61K 39/464406 (2023.05); A61K 39/464412 (2023.05); A61K 39/464471 (2023.05); C07K 14/7051 (2013.01); C07K 14/70578 (2013.01); C07K 16/2803 (2013.01); C07K 16/3061 (2013.01); C07K 16/3084 (2013.01); C07K 16/32 (2013.01); C12N 5/0638 (2013.01); C12N 15/1137 (2013.01); C07K 2317/622 (2013.01); C07K 2317/92 (2013.01); C07K 2319/03 (2013.01); C12N 2310/14 (2013.01)] 8 Claims
 
1. Isolated T cells comprising a nucleic acid molecule encoding a chimeric antigen receptor, wherein said T cells comprise at least one inhibitory nucleic acid molecule for CBL and at least one inhibitory nucleic acid molecule for CBL-B, and wherein the expression of CBL and CBL-B is inhibited in said T cells,
wherein said inhibitory nucleic acid molecule for CBL and said inhibitory nucleic acid molecule for CBL-B are selected from the group consisting of antisense, siRNA, shRNA, and miRNA,
wherein said chimeric antigen receptor comprises SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6,
wherein said inhibitory nucleic acid molecule for CBL comprises or is complementary to a nucleotide sequence selected from the group consisting of AGCAGCTAGTATGTTTTATTAT (SEQ ID NO: 11), TCAGTGGTTCCAAGATTTCAA (SEQ ID NO: 12), and GGCGAAACCTAACCAAACT (SEQ ID NO: 13):
wherein said inhibitory nucleic acid molecule for CBL-B comprises or is complementary to a nucleotide sequence selected from the group consisting of: AGGTGAAAATGTCAAAACTAA (SEQ ID NO: 16), CAGTGAGAATGAGTACTTTA (SEQ ID NO: 17), and GACCATACCTCATAACAAG (SEQ ID NO: 18).