Methods and compositions for treating cancer
AssigneeCrispr Therapeutics AG
InventorsJonathan Alexander Terrett, Demetrios Kalaitzidis, Mary-Lee Dequéant, Zinkal Samir Padalia
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Abstract
Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.
Claims181
An engineered T cell comprising a disrupted CD70 gene and a nucleic acid encoding a chimeric antigen receptor (CAR) that does not bind CD70.
An engineered T cell comprising:
- (i) a disrupted TRAC gene;
- (ii) a disrupted β2M gene;
- (iii) a disrupted CD70 gene;
- and
- (iv) a nucleic acid encoding a CAR that binds CD70.
An engineered T cell comprising:
- (i) a disrupted TRAC gene, wherein the disrupted TRAC gene comprises a nucleic acid encoding a CAR comprising the amino acid sequence set forth in SEQ ID NO:
- 46;
- (ii) a disrupted β2 M gene;
- and
- (iii) a disrupted CD70 gene.
An engineered T cell comprising:
- (i) a disrupted TRAC gene, wherein the disrupted TRAC gene comprises a nucleic acid encoding a CAR, wherein the nucleic acid sequence is at least 90% identical to SEQ ID NO:
- 45;
- (ii) a disrupted β2 M gene;
- and
- (iii) a disrupted CD70 gene.
An engineered T cell comprising:
- (i) a disrupted TRAC gene comprising a nucleic acid sequence at least 90% identical to SEQ ID NO:
- 44;
- (ii) a disrupted β2 M gene;
- and
- (iii) a disrupted CD70 gene.
A population of cells comprising engineered T cells, wherein the engineered T cells comprise a disrupted CD70 gene and a nucleic acid encoding a CAR that does not bind CD70.
A population of cells comprising engineered T cells, wherein the engineered T cells comprise:
- (i) a disrupted TRAC gene;
- (ii) a disrupted β2 M gene;
- (iii) a disrupted CD70 gene;
- and
- (iv) a nucleic acid encoding a CAR that binds CD70.
A population of cells comprising engineered T cells, wherein the engineered T cells comprise:
- (i) a disrupted TRAC gene;
- (ii) a disrupted β2 M gene;
- (iii) a disrupted CD70 gene
- (iv) a nucleic acid encoding a CAR comprising (a) an ectodomain that comprises an anti-CD70 scFv, (b) a CD8 transmembrane domain, and (c) an endodomain that comprises a 41BB co-stimulatory domain and a CD3z signaling domain.
A population of cells comprising engineered T cells, wherein the engineered T cells comprise:
- (i) a disrupted TRAC gene, wherein the disrupted TRAC gene comprises a nucleic acid encoding a CAR comprising the amino acid sequence set forth in SEQ ID NO:
- 46;
- (ii) a disrupted β2 M gene;
- and
- (iii) a disrupted CD70 gene.
A population of cells comprising engineered T cells, wherein the engineered T cells comprise:
- (i) a disrupted TRAC gene, wherein the disrupted TRAC gene comprises a nucleic acid encoding a CAR, wherein the nucleic acid sequence is at least 90% identical to SEQ ID NO:
- 45;
- (ii) a disrupted β2M gene;
- and
- (iii) a disrupted CD70 gene.
A population of cells comprising engineered T cells, wherein the engineered T cells comprise:
- (i) a disrupted TRAC gene comprising a nucleic acid sequence at least 90% identical to SEQ ID NO:
- 44;
- (ii) a disrupted β2M gene;
- and
- (iii) a disrupted CD70 gene.
A method of treating cancer in a subject, comprising administering to the subject a population of cells comprising engineered T cells, wherein the engineered T cells comprise:
- (i) a disrupted TRAC gene, wherein the disrupted TRAC gene comprises a nucleic acid encoding a CAR comprising the amino acid sequence set forth in SEQ ID NO:
- 46;
- (ii) a disrupted β2 M gene;
- and
- (iii) a disrupted CD70 gene,
- thereby treating the cancer in the subject.
A method of treating cancer in a subject, comprising administering to the subject a population of cells comprising engineered T cells, wherein the engineered T cells comprise:
- (i) a disrupted TRAC gene, wherein the disrupted TRAC gene comprises a nucleic acid encoding a CAR, wherein the nucleic acid sequence is at least 90% identical to SEQ ID NO:
- 45;
- (ii) a disrupted β2 M gene;
- and
- (iii) a disrupted CD70 gene,
- thereby treating the cancer in the subject.
A method of treating cancer in a subject, comprising administering to the subject a population of cells comprising engineered T cells, wherein the engineered T cells comprise:
- (i) a disrupted TRAC gene comprising a nucleic acid sequence at least 90% identical to SEQ ID NO:
- 44;
- (ii) a disrupted β2 M gene;
- and
- (iii) a disrupted CD70 gene,
- thereby treating the cancer in the subject.
A method for producing an engineered T cell, the method comprising:
- (a) delivering to a T cell
- an RNA-guided nuclease,
- a gRNA targeting a CD70 gene, and
- a vector comprising a donor template that comprises a nucleic acid encoding a CAR;
- and
- (b) producing an engineered T cell comprising a disrupted CD70 gene and expressing the CAR.
A method for producing an engineered T cell, the method comprising
- (a) delivering to a T cell
- an RNA-guided nuclease,
- a gRNA targeting a TRAC gene,
- a gRNA targeting a β2M gene,
- a gRNA targeting a CD70 gene, and
- a vector comprising a donor template that comprises a nucleic acid encoding a CAR;
- and
- (b) producing an engineered T cell.
A method for producing an engineered T cell for immunotherapy against a target cell, comprising:
- (a) disrupting a CD70 gene in a T cell, and
- (b) expressing a CAR that binds to an antigen expressed on the target cell, wherein the antigen is not CD70.
A method of increasing proliferation of T cells, comprising disrupting the CD70 gene in the T cells.
A method of reducing exhaustion of T cells, comprising disrupting the CD70 gene in the T cells.
Dependencies are inferred from the claim text.