IP Library › Granted Patent US 12,448,431
Granted Patent B2
US 12,448,431 · App. 17/733,226 · Granted Oct 21, 2025

Fully-human T-cell receptor specific for the 369-377 epitope derived from the Her2/neu (ERBB2) receptor protein

Inventor: Daniel J. Powell, Jr. (Bala Cynwyd, PA)
Assignee: The Trustees of the University of Pennsylvania
C07K14/7051C07K14/4705C07K14/82C07K16/28C12N9/12
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Quick Facts
Patent No.
US 12,448,431
App. No.
17/733,226
Granted
Oct 21, 2025
Kind
B2
Abstract

The present invention relates to compositions and methods for treating HER2/Neu (ERBB2) expressing cancer cells. In some embodiments, the invention includes an isolated T cell receptor (TCR) having high affinity for and that specifically binds ERBB2 369-377 epitope on a target cell. Other embodiments include a T cell or a population of T cells modified to express ERBB2-specific TCR. Further embodiments include methods of using ERBB2-specific TCR gene transfer for treating ERBB2 expressing cancer cells. Also included are methods and pharmaceutical compositions comprising the modified T cells for adoptive therapy.

Claims (20)

1. A purified T cell receptor (TCR) having affinity for a tyrosine-protein kinase HER2/Neu (ERBB2) on a target cell, wherein the purified TCR comprises: a TCR alpha chain comprising the amino acid sequence set forth in SEQ ID NO: 6 and a TCR beta chain comprising the amino acid sequence set forth in SEQ ID NO:7.

2. The purified TCR of claim 1 , wherein the TCR binds an epitope of ERBB2 receptor protein comprising the amino acid sequence set forth in SEQ ID NO: 9.

3. The purified TCR of claim 1 , wherein the target cell is HLA-A2+.

4. The purified TCR of claim 1 , wherein the TCR comprises at least one disulfide bond.

5. The purified TCR of claim 1 , wherein the TCR alpha and beta chains are connected by a peptide linker.

6. A pharmaceutical composition comprising the purified T cell receptor (TCR) of claim 1 , and a pharmaceutically acceptable carrier.

7. A recombinant expression vector comprising at least one nucleotide sequence encoding the purified TCR of claim 1 .

8. A modified mammalian cell comprising the purified TCR of claim 1 .

9. The modified mammalian cell of claim 8 , wherein the cell is selected from the group consisting of a peripheral blood mononuclear cell, a cord blood cell, a primary T cell, and a cell of a T cell line.

10. The modified mammalian cell of claim 8 , wherein the cell is a tumor infiltrating lymphocyte (TIL).

11. A population of cells comprising the modified mammalian cell of claim 10 .

12. The modified mammalian cell of claim 8 , wherein the mammalian cell is a human cell.

13. The modified mammalian cell of claim 8 , wherein the modified cell is a CD8 + T cell.

14. The modified mammalian cell of claim 11 , wherein the target cell is HLA-A2 + .

15. A purified T cell receptor (TCR) having affinity for a tyrosine-protein kinase HER2/Neu (ERBB2) on a target cell, wherein the purified TCR comprises: a TCR alpha chain comprising the amino acid sequence set forth in SEQ ID NO: 2 and a TCR beta chain comprising the amino acid sequence set forth in SEQ ID NO:4.

16. The purified TCR of claim 15 , wherein the TCR binds an epitope of ERBB2 receptor protein comprising the amino acid sequence set forth in SEQ ID NO: 9.

17. The purified TCR of claim 15 , wherein the target cell is HLA-A2+.

18. The purified TCR of claim 15 , wherein the TCR comprises at least one disulfide bond.

19. The purified TCR of claim 15 , wherein the TCR alpha and beta chains are connected by a peptide linker.

20. A pharmaceutical composition comprising the purified T cell receptor (TCR) of claim 15 , and a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 10, 2025
From: POWELL, DANIEL J., JR.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 072212/0852 →
Continuity (4)
Division 16534344 · Aug 7, 2019
Division 15550811
Provisional Application 62116864 · Feb 16, 2015
Related Publication 20220332787A1 · Oct 20, 2022
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