US 12,227,756 B2
Engineered regulatory T cell
Hans Stauss, London (GB); Graham P. Wright, London (GB); and Jenny L. McGovern, London (GB)
Assigned to UCL Business Ltd, London (GB)
Appl. No. 17/048,587
Filed by UCL Business Ltd, London (GB)
PCT Filed Apr. 17, 2019, PCT No. PCT/GB2019/051097
§ 371(c)(1), (2) Date Oct. 17, 2020,
PCT Pub. No. WO2019/202322, PCT Pub. Date Oct. 24, 2019.
Claims priority of application No. 1806330 (GB), filed on Apr. 18, 2018; and application No. 1806331 (GB), filed on Apr. 18, 2018.
Prior Publication US 2021/0145884 A1, May 20, 2021
Int. Cl. A61K 35/17 (2015.01); A61K 39/00 (2006.01); C07K 14/725 (2006.01); C07K 14/74 (2006.01); C12N 5/0783 (2010.01); C12N 15/87 (2006.01); A61K 35/12 (2015.01); A61K 38/00 (2006.01)
CPC C12N 15/87 (2013.01) [A61K 35/17 (2013.01); A61K 39/4611 (2023.05); A61K 39/4621 (2023.05); A61K 39/4632 (2023.05); A61K 39/46433 (2023.05); C07K 14/7051 (2013.01); C07K 14/70539 (2013.01); C12N 5/0637 (2013.01); A61K 2035/122 (2013.01); A61K 38/00 (2013.01); C12N 2510/00 (2013.01)] 11 Claims
 
1. An isolated engineered human regulatory T cell (Treg) comprising a T cell receptor (TCR) which is capable of specifically binding to a peptide which comprises MBP 111-129 (SEQ ID NO: 3) when the peptide is presented by a HLA-DRB1*0401 molecule, wherein the TCR comprises an α chain and a β chain,
wherein the α chain of the TCR comprises complementarity determining regions (CDRs) CDR1α, CDR2α, and CDR3α, having the following amino acid sequences:
 
(SEQ ID NO: 7)
 
CDRlα - TISGTDY
 
 
 
(SEQ ID NO: 8)
 
CDR2α - GLTSN
 
 
 
(SEQ ID NO: 9)
 
CDR3α - TVYGGATNKLIFGTGTLLAVQPNIQNPD;
and
wherein the β chain of the TCR comprises CDRs CDR1β, CDR2β, and CDR3β, having the following amino acid sequences:
 
(SEQ ID NO: 10)
 
CDR1β - DFQATT
 
 
 
(SEQ ID NO: 11)
 
CDR2β - SNEGSKA
 
 
 
(SEQ ID NO: 12)
 
CDR3β - SARGGSYNSPLHFGNGTRLTVTE;
and
wherein the engineered human Treg comprises an expression vector encoding the TCR and a human FOXP3 polypeptide comprising the amino acid sequence of SEQ ID NO: 17 or 25.