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US 2026/0158142 A1Published application
Cell therapy for alzheimer's disease
AssigneeBoard of Regents of the University of Nebraska
InventorsHoward GENDELMAN, R. Lee MOSLEY, Pravin YEAPURI, Jatinkumar MACHHI
Life of this patent
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Abstract
Provided are engineered cells that include a T cell receptor (TCR) or antigen-binding fragment thereof that binds to amyloid beta, and methods of engineering and using such cells, such as in methods of treatment, diagnosis, and monitoring of therapeutic effectiveness, of diseases or conditions, such as those associated with amyloid beta, e.g., Alzheimer's Disease.
Claims212
An engineered cell, comprising a heterologous T cell receptor (TCR) or antigen-binding fragment thereof,
- wherein the heterologous TCR or antigen-binding fragment thereof comprises an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, and
- wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 12, 13, and 14, respectively;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 15, 16, and 17, respectively.
2 more elements
An engineered cell, comprising a heterologous T cell receptor (TCR) or antigen-binding fragment thereof,
- wherein the heterologous TCR or antigen-binding fragment thereof comprises an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, and
- wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 2 or 5;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 4 or 8.
2 more elements
An engineered cell, comprising:
- a heterologous T cell receptor (TCR) or antigen-binding fragment thereof, wherein the heterologous TCR or antigen-binding fragment thereof comprises an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, and wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 12, 13, and 14, respectively;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 15, 16, and 17, respectively;
- and
- a genetic disruption in a T Cell Receptor Alpha Constant (TRAC) gene and/or a T Cell Receptor Beta Constant (TRBC) gene.
3 more elements
An engineered cell, comprising:
- a heterologous T cell receptor (TCR) or antigen-binding fragment thereof, wherein the heterologous TCR or antigen-binding fragment thereof comprises an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, and wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 2 or 5;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 4 or 8;
- and
- a genetic disruption in a T Cell Receptor Alpha Constant (TRAC) gene and/or a T Cell Receptor Beta Constant (TRBC) gene.
3 more elements
An engineered regulatory T (Treg) cell, comprising:
- a heterologous T cell receptor (TCR) or antigen-binding fragment thereof, wherein the heterologous TCR or antigen-binding fragment thereof comprises an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, and wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 12, 13, and 14, respectively;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 15, 16, and 17, respectively;
- and
- a genetic disruption in a T Cell Receptor Alpha Constant (TRAC) gene and/or a T Cell Receptor Beta Constant (TRBC) gene.
3 more elements
An engineered regulatory T (Treg) cell, comprising:
- a heterologous T cell receptor (TCR) or antigen-binding fragment thereof, wherein the heterologous TCR or antigen-binding fragment thereof comprises an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, and wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 2 or 5;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 4 or 8;
- and
- a genetic disruption in a T Cell Receptor Alpha Constant (TRAC) gene and/or a T Cell Receptor Beta Constant (TRBC) gene.
3 more elements
An engineered cell, comprising:
- a nucleic molecule encoding a heterologous T cell receptor (TCR) or antigen-binding fragment thereof, wherein the heterologous TCR or antigen-binding fragment thereof comprises an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, and wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 12, 13, and 14, respectively;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 15, 16, and 17, respectively;
- and
- a genetic disruption in a T Cell Receptor Alpha Constant (TRAC) gene and/or a T Cell Receptor Beta Constant (TRBC) gene.
3 more elements
An engineered cell, comprising:
- a nucleic acid molecule encoding a heterologous T cell receptor (TCR) or antigen-binding fragment thereof, wherein the heterologous TCR or antigen-binding fragment thereof comprises an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, and wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 2 or 5;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 4 or 8;
- and
- a genetic disruption in a T Cell Receptor Alpha Constant (TRAC) gene and/or a T Cell Receptor Beta Constant (TRBC) gene.
3 more elements
A T cell receptor (TCR) or antigen-binding fragment thereof, comprising an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 12, 13, and 14, respectively;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs:
- 15, 16, and 17, respectively.
A T cell receptor (TCR) or antigen-binding fragment thereof, comprising an alpha chain comprising a variable alpha (Vα) region and a beta chain comprising a variable beta (Vβ) region, wherein the Vα region comprises a complementarity determining region 1 (CDR-1), CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 2 or 5;
- and the Vβ region comprises a CDR-1, CDR-2, and CDR-3 comprising the CDR-1, CDR-2, and CDR-3 amino acid sequences contained within the amino acid sequence of SEQ ID NO:
- 4 or 8.
A method of engineering a cell, comprising:
- introducing, into the cell, one or more agents capable of editing and/or disrupting one or more endogenous genes in the cell, wherein each of the one or more endogenous genes comprises a first flanking sequence and a second flanking sequence;
- and
- introducing, into the cell, one or more nucleic acid molecules, wherein each of the one or more nucleic acid molecules comprises:
- (i) a first homology arm and a second homology arm that are homologous to the first flanking sequence and the second flanking sequence of one of the one or more endogenous genes, and (ii) a nucleic acid sequence of interest that is located between the first homology arm and the second homology arm.
1 more element
A method of engineering a cell, comprising:
- introducing, into the cell, one or more agents capable of inducing a DNA break in one or more endogenous genes in the cell, wherein each of the one or more endogenous genes comprises a first flanking sequence and a second flanking sequence;
- and
- introducing, into the cell, one or more nucleic acid molecules, wherein each of the one or more nucleic acid molecules comprises:
- (i) a first homology arm and a second homology arm that are homologous to the first flanking sequence and the second flanking sequence of one of the one or more endogenous genes, and (ii) a nucleic acid sequence of interest that is located between the first homology arm and the second homology arm.
1 more element
Dependencies are inferred from the claim text.