Granted Patent
B2
US 12,448,429 · App. 17/430,938 · Granted Oct 21, 2025
T cell receptors specific to b-cell maturation antigen for treatment of cancer
Inventors:
Jooeun Bae (West Roxbury, MA); Nikhil C. Munshi (Needham, MA); Kenneth C. Anderson (Wellesley, MA)
Assignee:
Dana-Farber Cancer Institute, Inc.
C07K14/7051A61K39/001117A61K40/11A61K40/32A61K40/4215A61P35/00C12N5/0636A61K35/17A61K2239/48C12N5/16C12N15/63
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Abstract
This disclosure relates to T cell receptors (e.g., T cell receptors comprising alpha chains and beta chains) specific to B-cell maturation antigen (BCMA), T cells comprising same, and methods of use thereof.
Claims (20)
1. A T cell receptor (TCR) comprising:
(a) a T cell receptor alpha chain (TCA) variable domain which is specific for B-cell maturation antigen (BCMA) and which comprises the amino acid sequence set forth in SEQ ID NO:27 and a T cell receptor beta chain (TCB) variable domain comprising the amino acid sequence set forth in SEQ ID NO: 19;
(b) a TCA variable domain comprising the amino acid sequence set forth in SEQ ID NO: 28 and a TCB variable domain comprising the amino acid sequence set forth in SEQ ID NO:20, or differing by 1 to 10 amino acids;
(c) a TCA variable domain comprising the amino acid sequence set forth in SEQ ID NO: 29 and a TCB variable domain comprising the amino acid sequence set forth in SEQ ID NO:21, or differing by 1 to 10 amino acids;
(d) a TCA variable domain comprising the amino acid sequence set forth in SEQ ID NO: 30 and a TCB variable domain comprising the amino acid sequence set forth in SEQ ID NO:22;
(e) a TCA variable domain comprising the amino acid sequence set forth in SEQ ID NO: 31 and a TCB variable domain comprising the amino acid sequence set forth in SEQ ID NO:23, or differing by 1 to 10 amino acids;
(f) a TCA variable domain comprising the amino acid sequence set forth in SEQ ID NO: 32 and a TCB variable domain comprising the amino acid sequence set forth in SEQ ID NO:24;
(g) a TCA variable domain comprising the amino acid sequence set forth in SEQ ID NO: 33 and a TCB variable domain comprising-the amino acid sequence set forth in SEQ ID NO:25 or;
(h) a TCA variable domain comprising the amino acid sequence set forth in SEQ ID NO: 34 and a TCB variable domain comprising the amino acid sequence set forth in SEQ ID NO:26.
2. A composition comprising the TCR of claim 1 and a second agent.
3. A cultured cell comprising the TCR of claim 1 .
4. A T cell comprising the TCR of claim 1 .
5. A method of killing a target cell, the method comprising:
contacting the target cell with the T cell of claim 4 , wherein the target cell expresses or overexpresses B-cell maturation antigen (BCMA) and expresses human leukocyte antigen A (HLA-A).
6. The TCR of claim 1 , wherein the TCR is specific for a peptide of human BCMA (SEQ ID NO: 38).
7. The TCR of claim 1 , wherein the TCR is specific for the heteroclitic BCMA72-80 YLMFLLRKI peptide (SEQ ID NO:37).
8. The TCR of claim 1 , wherein the TCR is specific for the heteroclitic BCMA72-80 YLMFLLRKI peptide (SEQ ID NO:37) bound to HLA-A2.
9. The TCR of claim 1 , wherein the TCR is a single-chain variable fragment (scFv).
10. A method of treating a human subject having a B-cell maturation antigen (BCMA)-expressing hematological cancer, the method comprising administering to the human subject the T cell of claim 4 .
11. A pharmaceutical composition comprising the T cell of claim 4 and a pharmaceutically acceptable carrier.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 28, 2022
From: BAE, JOOEUN; MUNSHI, NIKHIL C.; ANDERSON, KENNETH C.
To: DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 060045/0073 →
Continuity (2)
Provisional Application
62814622
· Mar 6, 2019
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