Chimeric polypeptides and methods of use
AssigneeBoard of Regents, The University of Texas System
InventorsSattva S. NEELAPU, Jingwei LIU, Sridevi PATCHVA, Yongfu TANG
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Abstract
Aspects of the present disclosure provide compositions and methods for detecting, isolating, depleting, and/or purifying cells, including polypeptides, including chimeric polypeptides, useful in such methods. Various chimeric polypeptides are disclosed, along with use of such polypeptides as selection markers, transduction markers, and/or safety switches. Also disclosed are cells, including therapeutic cells such as T cells, NK cells, NKT cells, and iPSCs, comprising polynucleotides encoding one or more chimeric polypeptides.
Claims358
A chimeric polypeptide comprising:
- (a) an extracellular domain from B-cell maturation antigen (BCMA);
- (b) a hinge region from programmed cell death 1 ligand 1 (PDL1);
- (c) a transmembrane domain;
- and
- (d) an intracellular region.
A chimeric polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:1.
A chimeric polypeptide comprising SEQ ID NO:1.
A chimeric polypeptide consisting of SEQ ID NO:1.
A chimeric polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:38.
A chimeric polypeptide comprising SEQ ID NO:38.
A chimeric polypeptide consisting of SEQ ID NO:38.
A chimeric polypeptide comprising:
- (a) a tissue-type plasminogen activator (tPA) signal peptide;
- (b) an extracellular domain from BCMA;
- (c) a hinge region;
- (d) a transmembrane domain;
- and
- (e) an intracellular region.
A chimeric polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:3.
A chimeric polypeptide comprising SEQ ID NO:3.
A chimeric polypeptide consisting of SEQ ID NO:3.
A chimeric polypeptide comprising:
- (a) an extracellular domain from CD30;
- (b) a transmembrane domain from CD30;
- and
- (c) an intracellular region from BCMA.
A chimeric polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:9.
A chimeric polypeptide comprising SEQ ID NO:9.
A chimeric polypeptide consisting of SEQ ID NO:9.
A chimeric polypeptide comprising:
- (a) a signal peptide that is not a Her2 signal peptide;
- (b) an extracellular domain from Her2;
- and
- (c) a transmembrane domain from Her2.
A chimeric polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:11.
A chimeric polypeptide comprising SEQ ID NO:11.
A chimeric polypeptide consisting of SEQ ID NO:11.
An engineered immune cell comprising a nucleic acid encoding a Trop2 polypeptide.
A chimeric polypeptide comprising:
- (a) a signal peptide;
- (b) an extracellular region comprising (i) EGFR domain III and (ii) a portion of EGFR domain IV having a length of less than 100 amino acids;
- (c) a hinge region;
- and
- (d) a transmembrane domain.
A chimeric polypeptide comprising an amino acid sequence at least 95% identical to SEQ ID NO:15.
A chimeric polypeptide comprising SEQ ID NO:15.
A chimeric polypeptide consisting of SEQ ID NO:15.
A method for detecting, isolating, depleting, or purifying a cell, the cell comprising:
- (a) an extracellular domain from B-cell maturation antigen (BCMA);
- (b) a hinge region from programmed cell death 1 ligand 1 (PDL1);
- (c) a transmembrane domain;
- and
- (d) an intracellular region,
- the method comprising contacting the cell with a BCMA-binding protein.
A method for detecting, isolating, depleting, or purifying a cell, the cell comprising:
- (a) a tissue-type plasminogen activator (tPA) signal peptide;
- (b) an extracellular domain from BCMA;
- (c) a hinge region;
- (d) a transmembrane domain;
- and
- (e) an intracellular region,
- the method comprising contacting the cell with a BCMA-binding protein.
A method for detecting, isolating, depleting, or purifying a cell, the cell comprising:
- (a) an extracellular domain from CD30;
- (b) a transmembrane domain from CD30;
- (c) an intracellular region from BCMA,
- the method comprising contacting the cell with a CD30-binding protein.
A method for detecting, isolating, depleting, or purifying a cell, the cell comprising:
- (a) a signal peptide that is not a Her2 signal peptide;
- (b) an extracellular domain from Her2;
- (c) a transmembrane domain from Her2,
- the method comprising contacting the cell with a Her2-binding protein.
A method for detecting, isolating, depleting, or purifying an engineered immune cell, the engineered immune cell comprising a Trop2 polypeptide, the method comprising contacting the cell with a Trop2-binding protein.
A method for detecting, isolating, depleting, or purifying a cell, the cell comprising:
- (a) a signal peptide;
- (b) an extracellular region comprising (i) EGFR domain III and (ii) a portion of EGFR domain IV having a length of less than 100 amino acids;
- (c) a hinge region;
- and
- (d) a transmembrane domain,
- the method comprising contacting the cell with an EGFR-binding protein.
An expression construct, comprising sequence that encodes a CD30 fusion protein, wherein the fusion protein comprises at least part of the CD30 extracellular domain fused to an intracellular domain that comprises endocytosis or internalization activity.
A method of identifying CD30-positive cells that are transduced or transfected with (1) a heterologous CD30 gene;
- (2) a CD30 fusion protein comprising at least part of the CD30 extracellular domain;
- or (3) a combination of heterologous BCL6 and one or more Bcl2 family genes, comprising the steps of:
- transducing or transfecting cells with (1) a heterologous CD30 gene;
- (2) a CD30 fusion protein comprising at least part of the CD30 extracellular domain;
- or (3) a combination of heterologous BCL6 and one or more Bcl2 family genes;
- exposing the cells to an effective amount of an agent that binds CD30;
- and
- directly or indirectly detecting the binding of the agent to CD30 on the surface of the cells.
A method of manufacturing immune cells for adoptive cell therapy, comprising the steps of:
- (a) transducing or transfecting immune cells with (1) heterologous CD30 protein;
- (2) a CD30 fusion protein;
- or (3) a combination of heterologous BCL6 and one or more Bcl2 family genes, wherein the immune cells respectively express (1) CD30;
- (2) the CD30 fusion protein;
- or (3) CD30;
- and
- (b) transducing or transfecting the immune cells with one or more therapeutic proteins.
A method of reducing or preventing one or more deleterious effects from a cellular therapy in an individual, comprising the step of targeting CD30 expressed on the surface of cells of the cellular therapy.
A method of inhibiting the activity of cells, comprising the step of exposing cells that are transduced or transfected with a combination of heterologous BCL6 and one or more Bcl2 family genes to an effective amount of an agent that binds CD30.
A method of inhibiting the activity of cells, comprising the step of exposing cells that are transduced or transfected with a CD30 fusion protein comprising at least part of the CD30 extracellular domain to an effective amount of an agent that binds CD30.
Dependencies are inferred from the claim text.