IP Library › Granted Patent US 12,383,581
Granted Patent B2
US 12,383,581 · App. 17/767,831 · Granted Aug 12, 2025

Compositions and methods for targeting CD13 and TIM-3 with CAR T cells to treat acute myeloid leukemia

Inventors: Xianxin Hua (Wynnewood, PA); Xin He (Philadelphia, PA); Xuyao Zhang (Shanghai, CN)
Assignee: The Trustees of the University of Pennsylvania
A61K35/17A61K40/11A61K40/31A61K40/421A61K40/4224A61K40/4244A61P35/02C07K16/2803C07K16/40A61K2239/13A61K2239/17A61K2239/21A61K2239/22A61K2239/29A61K2239/48
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Quick Facts
Patent No.
US 12,383,581
App. No.
17/767,831
Granted
Aug 12, 2025
Kind
B2
Abstract

The present invention includes compositions and methods for treating AML utilizing bispecific CARs. In certain aspects, the invention includes a bispecific split CAR which binds CD13 and TIM-3 on AML cells.

Claims (15)

1. A bispecific chimeric antigen receptor (CAR) comprising a first antigen binding domain capable of binding CD13, a first intracellular domain, a second antigen binding domain capable of binding TIM-3, a transmembrane domain, and a second intracellular domain, wherein the first antigen binding domain comprises the amino acid sequence set forth in SEQ ID NO: 1.

2. The bispecific CAR of claim 1 , wherein the first and/or second antigen binding domain is selected from the group consisting of an antibody, a nanobody, a Fab, and an scFv.

3. The bispecific CAR of claim 1 , wherein the second antigen binding domain comprises the amino acid sequence set forth in SEQ ID NO: 6.

4. The bispecific CAR of claim 1 , wherein the second antigen binding domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 20, 22, 24, 26, 28, 30, and 32.

5. The bispecific CAR of claim 1 , wherein the second antigen binding domain is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO: 19, 21, 23, 25, 27, 29, and 31.

6. The bispecific CAR of claim 1 , wherein the transmembrane domain comprises CD28.

7. The bispecific CAR of claim 1 , wherein the first intracellular domain is selected from the group consisting of 4-1BB, CD28, and CD3 zeta.

8. The bispecific CAR of claim 1 , wherein the second intracellular domain is selected from the group consisting of 4-1BB, CD28, and CD3 zeta.

9. The bispecific CAR of claim 1 , wherein the bispecific CAR further comprises a hinge domain selected from the group consisting of a CD8 hinge, an IgG3s hinge, and an IgG4m hinge.

10. The bispecific CAR of claim 1 , wherein the bispecific CAR is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NOs: 33-39.

11. A modified T cell or precursor thereof, comprising the bispecific CAR of claim 1 .

12. The cell of claim 11 , wherein the T cell is autologous.

13. A nucleic acid encoding the bispecific CAR of claim 1 .

14. A method for treating cancer in a subject in need thereof, the method comprising administering to the subject a modified T cell or precursor thereof comprising the bispecific CAR of claim 1 .

15. The method of claim 14 , wherein the cancer is acute myeloid leukemia (AML).

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2025
From: HUA, XIANXIN; HE, XIN; ZHANG, XUYAO
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 070843/0768 →
Continuity (2)
Provisional Application 62913915 · Oct 11, 2019
Related Publication 20240082302A1 · Mar 14, 2024
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