IP Library › Granted Patent US 12,441,787
Granted Patent B2
US 12,441,787 · App. 17/040,387 · Granted Oct 14, 2025

Neutralization of human cytokines with membrane-bound anti-cytokine non-signaling binders expressed in immune cells

Inventors: Hong Ji Adrian Tan (Singapore, SG); Dario Campana (Singapore, SG)
Assignee: NATIONAL UNIVERSITY OF SINGAPORE
C07K16/248A61K40/11A61K40/31A61K40/4211A61K40/4234A61P37/06C07K14/7051C07K14/70517C07K14/70578C07K16/2803C12N5/0636A61K2239/29A61K2239/31A61K2239/38A61K2239/48C07K2317/21C07K2317/622C07K2319/02C07K2319/03
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Quick Facts
Patent No.
US 12,441,787
App. No.
17/040,387
Granted
Oct 14, 2025
Kind
B2
Abstract

Transgenic T cells and vectors for making transgenic T cells are described. The vectors can include a nucleic acid encoding a membrane-bound anti-IL6 (mb-alL6) single chain variable fragment (scFv), and the transgenic T cells can express mb-alL6. The transgenic T cells are useful for suppressing proliferation of IL-6-dependent cells, reducing IL-6 concentration, or both. In one embodiment, the vector is a bicistronic construct encoding the mb-alL6 and an anti-CD19-41 BB-003ζ chimeric antigen receptor (CAR). In another embodiment, an anti-IL-6 scFv can be linked to a 41 BB and 003ζ domains to form an anti-IL-6 CAR. The transgenic T cells expressing said constructs can reduce the linker risk of cytokine release syndrome (CRS) in cancer patients being treated with CAR T cell or for the treatment of autoimmune diseases and inflammatory diseases in which cytokines are involved in pathogenesis.

Claims (11)

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.

2. The method of claim 1 , wherein the mammal is a human.

3. The method of claim 1 , further comprising culturing the T cell to generate new T cells that express the mb-aIL6.

4. The method of claim 1 , wherein the method reduces risk of cytokine release syndrome (CRS) in the mammal.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 7, 2020
From: TAN, HONG JI ADRIAN; CAMPANA, DARIO
To: NATIONAL UNIVERSITY OF SINGAPORE
Reel/Frame 053999/0633 →
Continuity (2)
Provisional Application 62651311 · Apr 2, 2018
Related Publication 20210017271A1 · Jan 21, 2021
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