US 12,441,787 B2
Neutralization of human cytokines with membrane-bound anti-cytokine non-signaling binders expressed in immune cells
Hong Ji Adrian Tan, Singapore (SG); and Dario Campana, Singapore (SG)
Assigned to NATIONAL UNIVERSITY OF SINGAPORE, Singapore (SG)
Appl. No. 17/040,387
Filed by National University of Singapore, Singapore (SG)
PCT Filed Mar. 29, 2019, PCT No. PCT/IB2019/052636
§ 371(c)(1), (2) Date Sep. 22, 2020,
PCT Pub. No. WO2019/193476, PCT Pub. Date Oct. 10, 2019.
Claims priority of provisional application 62/651,311, filed on Apr. 2, 2018.
Prior Publication US 2021/0017271 A1, Jan. 21, 2021
Int. Cl. C07K 16/24 (2006.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/42 (2025.01); A61P 37/06 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01)
CPC C07K 16/248 (2013.01) [A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/4211 (2025.01); A61K 40/4234 (2025.01); A61P 37/06 (2018.01); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70578 (2013.01); C07K 16/2803 (2013.01); C12N 5/0636 (2013.01); A61K 2239/29 (2023.05); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/48 (2023.05); C07K 2317/21 (2013.01); C07K 2317/622 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01)] 4 Claims
 
1. A method of reducing IL-6 concentration in a mammal being treated for cancer, the method comprising expressing a nucleic acid contained in a vector in a T cell, wherein the expressed nucleic acid contained within the vector encodes:
a) a chimeric antigen receptor (CAR); and
b) a membrane-bound anti-IL6 (mb-aIL6) comprising:
i) a CD8α signal peptide domain;
ii) an anti-IL-6 variable light chain domain comprising SEQ ID NO:4;
iii) an anti-IL-6 variable heavy chain domain comprising SEQ ID NO: 8;
iv) a linker domain joining the variable light chain domain and the variable heavy chain domain; and
v) a hinge and transmembrane domain.