Granted Patent
B2
US 12,233,090 · App. 18/623,246 · Granted Feb 25, 2025
Bispecific or-gate chimeric antigen receptor responsive to CD20 and CD19
Inventors:
Yvonne Y. Chen (Los Angeles, CA); Eugenia Zah (Los Angeles, CA); Michael C. Jensen (Seattle, WA)
A61K35/17A61K39/4611A61K39/4631A61K39/464412A61K39/464424C07K14/7051C07K14/70521C07K14/70596C07K16/2803C07K16/2887C07K16/46C12N5/0636A61K38/00A61K2039/505A61K2239/29A61K2239/48C07K2317/31C07K2317/622C07K2319/03C07K2319/40C12N2510/00
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Abstract
A CD20-OR-CD19 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD20-OR-CD19 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD20-OR-CD19 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.
Claims (32)
1. A polypeptide comprising a CD20-OR-CD19 chimeric antigen receptor (CAR), wherein the CAR comprises from N- to C-terminus:
a) an anti-CD20 scFv comprising a variable heavy domain and a variable light domain from SEQ ID NO: 3;
b) a (EAAAK (SEQ ID NO: 1)) n linker, wherein n is 1, 2, 3, 4, 5, or 6;
c) an anti-CD19 scFv comprising a variable light domain and a variable heavy domain from SEQ ID NO: 4;
d) a spacer domain;
e) a transmembrane domain;
f) a co-stimulatory domain of SEQ ID NO: 8; and
g) a CD3-zeta cytoplasmic signalling domain of SEQ ID NO: 9.
2. The polypeptide of claim 1 , wherein the (EAAAK) n linker is (EAAAK) 1 (SEQ ID NO: 1).
3. The polypeptide of claim 1 , wherein the (EAAAK) n linker is (EAAAK) 3 (SEQ ID NO: 17).
4. The polypeptide of claim 1 , wherein the (EAAAK) n linker is (EAAAK) 6 (SEQ ID NO: 14).
5. A nucleic acid encoding the polypeptide of claim 1 .
6. A viral vector comprising the nucleic acid of claim 5 .
7. The viral vector of claim 6 , wherein the vector is a lentiviral vector.
8. An isolated engineered cell comprising the nucleic acid of claim 5 .
9. The cell of claim 8 , wherein the cell is a T cell, a NK cell, or a NKT cell.
10. A polypeptide comprising a CD20-OR-CD19 chimeric antigen receptor (CAR), wherein the CAR comprises from N- to C-terminus:
a) an anti-CD20 scFv comprising a variable heavy domain and a variable light domain from SEQ ID NO: 3;
b) a flexible peptide linker consisting of Gly and Ser residues;
c) an anti-CD19 scFv comprising a variable light domain and a variable heavy domain from SEQ ID NO: 4;
d) a spacer domain;
e) a transmembrane domain;
f) a co-stimulatory domain of SEQ ID NO: 8; and
g) a CD3-zeta cytoplasmic signalling domain of SEQ ID NO: 9.
11. The polypeptide of claim 10 , wherein the linker comprises (G4S) 1 (SEQ ID NO: 15).
12. The polypeptide of claim 10 , wherein the linker comprises (G4S) 3 (SEQ ID NO: 16).
13. The polypeptide of claim 10 , wherein the linker comprises (G4S) 4 (SEQ ID NO: 19).
14. A nucleic acid encoding the polypeptide of claim 10 .
15. A viral vector comprising the nucleic acid of claim 14 .
16. The viral vector of claim 15 , wherein the vector is a lentiviral vector.
17. An isolated engineered cell comprising the nucleic acid of claim 14 .
18. The cell of claim 17 , wherein the cell is a T cell, a NK cell, or a NKT cell.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 28, 2024
From: JENSEN, MICHAEL C.
To: SEATTLE CHILDREN'S HOSPITAL DBA SEATTLE CHILDREN'S RESEARCH INSTITUTE
Reel/Frame 068424/0615 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 28, 2024
From: CHEN, YVONNE Y.; ZAH, EUGENIA
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 068424/0653 →
Continuity (5)
Continuation
15535972
Provisional Application
62091854
· Dec 15, 2014
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