Granted Patent B2

US 12,473,342 · App. 17/050,527 · Granted Nov 18, 2025

Inventors: Avery D. Posey (Philadelphia, PA); Carl H. June (Merion Station, PA); Robert D. Schwab (Bryn Mawr, PA)

Assignee: The Trustees of the University of Pennsylvania

C07K14/70507A61K40/11A61K40/22A61K40/31A61K40/4242C07K14/7051C07K14/70517C07K14/70521C07K14/70578C07K16/18A61K2239/38C07K2317/53C07K2317/622C07K2319/03

Abstract

Claims (30)

1 . An isolated chimeric antigen receptor (CAR) comprising an antigen binding domain specific for modified low-density lipoprotein (LDL), a transmembrane domain, and an intracellular domain, wherein the antigen binding domain comprises an scFv comprising the amino acid sequence set forth in SEQ ID NO: 6.

2 . The isolated CAR of claim 1 , wherein the modified LDL comprises oxidized LDL (OxLDL).

3 . The isolated CAR of claim 1 , wherein the modified LDL comprises an MDA/MDA-ApoB100 epitope present on oxidized LDL (OxLDL).

4 . The isolated CAR of claim 1 , wherein the modified LDL comprises modified ApoB100.

5 . The isolated CAR of claim 1 , wherein the modified LDL is selected from the group consisting of Cu-oxidized LDL, advanced glycation end products LDL (AGE-LDL), malondialdehyde-LDL, glycated-LDL, carbamylated LDL, desialylated LDL, apolipoprotein (a), and lipoprotein (a) (Lp-a), oxidized phosphatidylcholine containing oxidized phospholipids, 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC), 4-hydroxynonenal (HNE), oxidized cholesteryl ester (OxCE), and oxidized cardiolipin (OxCL).

6 . The isolated CAR of claim 1 , wherein the transmembrane domain is selected from the group consisting of CD28, CD8α, ICOS, and GITR.

7 . The isolated CAR of claim 1 , wherein the transmembrane domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 13, and SEQ ID NO: 14.

8 . The isolated CAR of claim 1 , wherein the intracellular domain is at least one selected from the group consisting of CD3zeta, CD28, 4-1BB, ICOS, GITR, and CD2.

9 . The isolated CAR of claim 1 , wherein the intracellular domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, and SEQ ID NO: 23.

10 . The isolated CAR of claim 1 , wherein the intracellular domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 24, and SEQ ID NO: 26.

11 . The isolated CAR of claim 1 , wherein the CAR further comprises a hinge domain.

12 . The isolated CAR of claim 1 , wherein the CAR further comprises a hinge domain comprising SEQ ID NO: 8.

13 . The isolated CAR of claim 1 , wherein the CAR comprises a 2D03 scFv, a CD8 α hinge domain, a CD28 transmembrane domain, a CD28 intracellular domain, and a CD3 zeta domain.

14 . The isolated CAR of claim 1 , wherein the CAR comprises a 2D03 scFv, a CD8α hinge domain, a CD8α transmembrane domain, a 4-1BB intracellular domain,

and a CD3 zeta domain.

15 . The isolated CAR of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 2.

16 . The isolated CAR of claim 1 , wherein the CAR comprises a 2D03 scFv, a CD8α hinge domain, an ICOS transmembrane domain, an ICOS intracellular domain, and a CD3 zeta domain.

17 . The isolated CAR of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 3.

18 . The isolated CAR of claim 1 , wherein the CAR comprises, a 2D03 scFv, a CD8α hinge domain, a GITR transmembrane domain, a GITR intracellular domain, and a CD3 zeta domain.

19 . The isolated CAR of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 4.

20 . The isolated CAR of claim 1 , wherein the CAR comprises a 2D03 scFv, a CD8α hinge domain, a CD8α transmembrane domain, a CD2 intracellular domain, and a CD3 zeta+domain.

21 . The isolated CAR of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 5.

22 . An isolated nucleic acid encoding the chimeric antigen receptor (CAR) of claim 1 .

23 . A vector comprising the isolated nucleic acid of claim 22 .

24 . A modified T cell comprising the isolated nucleic acid of claim 22 .

25 . The modified T cell of claim 24 , wherein the T cell is an autologous T cell.

26 . The modified T cell of claim 24 , wherein the T cell is a regulatory T (Treg) cell.

27 . The modified T cell of claim 24 , wherein the T cell is a CD4+ T cell.

28 . The modified T cell of claim 27 , wherein the CD4+ T cell is converted to a regulatory T (Treg) cell.

29 . An isolated chimeric antigen receptor (CAR) comprising an antigen binding domain specific for modified low-density lipoprotein (LDL), a transmembrane domain, and an intracellular domain, wherein the CAR comprises the amino acid sequence of SEQ ID NO: 1.

Continuity (2)

References Cited (20)