Chimeric antigen receptor cell
AssigneeUCL Business PLC
InventorsMartin Pulé, Weng-Kit Cheung
Life of this patent
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Abstract
The present invention relates to a cell which comprises a chimeric antigen receptor (CAR) comprising a binding domain which binds a first epitope of a tumour antigen; and a polynucleotide which encodes a bi-specific protein which comprises a first binding domain which binds a second epitope of said tumour antigen; and a second binding domain which binds a cell surface antigen. The present invention also provides CAR systems, nucleic acids, vectors, pharmaceutical compositions and pharmaceutical compositions for use in the treatment and/or prevention of disease.
Claims25
A cell which comprises;
- (i) a chimeric antigen receptor (CAR) comprising a binding domain which binds a first epitope of a tumour antigen;
- and
- (ii) a polynucleotide which encodes a bi-specific protein which comprises:
- a first binding domain which binds a second epitope of said tumour antigen;
- and
- a second binding domain which binds a cell surface antigen.
A cell according to any preceding claim, wherein the tumour antigen is not a cell surface tumour antigen, preferably said tumour antigen does not comprise a transmembrane domain;
- a lipid anchor such as a glycosylphosphatidylinositol (GPI)-anchor.
A cell according to any preceding claim, wherein the tumour antigen does not comprise a signal peptide.
A cell according to any preceding claim, wherein the tumour antigen is expressed at a higher level in the tumour compared with a corresponding, non-cancerous tissue, or wherein the antigen is tumour-specific.
A cell according to any preceding claim, wherein the first or second epitope of the tumour antigen comprises a tumour-specific mutation.
A cell according to any preceding claim, wherein the tumour antigen is a fusion protein, suitably said fusion protein may comprise at least two domains, wherein a first domain comprises the first epitope of a tumour antigen and a second domain comprises the second epitope of the tumour antigen.
A cell according to any preceding claim, wherein the first or second epitope of the tumour antigen comprises a tumour-specific post-translational modification.
A cell according to any preceding claim, wherein:
- a) the binding domain of the CAR binds a first epitope of a tumour antigen which is specific to the tumour;
- and/or
- b) the first binding domain of the bi-specific protein binds a second epitope of a tumour antigen which is specific to the tumour.
A cell according to any preceding claim wherein the cell is an immune effector cell, such as an alpha-beta T cell, a NK cell, a gamma-delta T cell, a cytokine induced killer cell or a macrophage.
A nucleic acid construct which comprises:
- (i) a first nucleic acid sequence which encodes a CAR comprising a binding domain which binds a first epitope of a tumour antigen;
- and
- (ii) a second nucleic acid sequence which encodes a bi-specific protein which comprises:
- a first binding domain which binds a second epitope of said tumour antigen;
- and
- a second binding domain which binds an epitope of a cell surface tissue antigen.
A kit of nucleic acid sequences comprising:
- (i) a first nucleic acid sequence which encodes a CAR comprising a binding domain which binds a first epitope of a tumour antigen;
- and
- (ii) a second nucleic acid sequence which encodes a bi-specific protein, which comprises:
- a first binding domain which binds a second epitope of said tumour antigen;
- and
- a second binding domain which binds an epitope of a cell surface tissue antigen.
A kit of vectors which comprises:
- (i) a first vector which comprises a nucleic acid sequence which encodes a CAR comprising a binding domain which binds a first epitope of a tumour antigen;
- and
- (ii) a second vector which comprises a nucleic acid sequence which encodes a bi-specific protein, which comprises:
- a first binding domain which binds a second epitope of said tumour antigen;
- and
- a second binding domain which binds an epitope of cell surface tissue antigen.
A CAR system comprising;
- (i) a receptor component comprising a binding domain which binds a first epitope of a tumour antigen, a transmembrane domain and a signaling domain;
- and
- ii) a bi-specific protein which comprises:
- a first binding domain which binds a second epitope of said tumour antigen;
- and
- a second binding domain which binds an epitope of a cell surface tissue antigen.
A bi-specific protein for use in treating cancer in combination with a CAR expressing cell, wherein:
- the bi-specific protein comprises:
- a first binding domain which binds a second epitope of said tumour antigen;
- and
- a second binding domain which binds an epitope of a cell surface tissue antigen;
- and
- the CAR comprises a binding domain which binds a first epitope of a tumour antigen.
A CAR expressing cell for use in treating cancer in combination with a bi-specific protein, wherein:
- the CAR comprises a binding domain which binds a first epitope of a tumour antigen;
- and
- the bi-specific protein comprises:
- a first binding domain which binds a second epitope of said tumour antigen;
- and
- a second binding domain which binds an epitope of a cell surface tissue antigen.
Dependencies are inferred from the claim text.