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US 2022/0025014 A1Published application
Dimerizing agent regulated immunoreceptor complexes
Assigneebluebird bio, Inc.
InventorsJORDAN JARJOUR, WAI-HANG LEUNG
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Abstract
The present disclosure provides improved compositions for adoptive T cell therapies targeting CD33 for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith. The present disclosure also relates to adoptive T cell therapies targeting CD33 and another target antigen for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.
Claims180
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain or a CD4 transmembrane domain;
- a CD137 co-stimulatory domain;
- and/or a CD3ζ primary signaling domain;
- and
- (b) a second polypeptide comprising:
- a binding domain that binds to CD33;
- an FKBP multimerization domain polypeptide or variant thereof;
- and a CD4 transmembrane domain or a CD8α transmembrane domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
8 more elements
A non-natural cell comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof, a CD8α transmembrane domain or a CD4 transmembrane domain;
- a CD137 co-stimulatory domain;
- and/or a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- a binding domain that binds to CD33;
- an FKBP multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or a CD8α transmembrane domain;
- and
- (c) a third polypeptide comprising:
- a binding domain that binds to a target antigen;
- an FK506 binding protein (FKBP) multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or an amnionless (AMN) transmembrane domain;
- wherein a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first polypeptide and the second polypeptide and the multimerization domains of the first polypeptide and the third polypeptide.
9 more elements
A non-natural cell comprising a polypeptide complex that comprises:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof, a CD8α transmembrane domain or a CD4 transmembrane domain;
- a CD137 co-stimulatory domain;
- and/or a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- a binding domain that binds to CD33;
- an FKBP multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or a CD8α transmembrane domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
6 more elements
A non-natural cell comprising a polypeptide complex that comprises:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof;
- a CD8α transmembrane domain or a CD4 transmembrane domain;
- a CD137 co-stimulatory domain;
- and/or a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- a binding domain that binds to CD33;
- an FKBP multimerization domain polypeptide or variant thereof;
- and a CD4 transmembrane domain or a CD8α transmembrane domain;
- (c) a third polypeptide comprising:
- a binding domain comprising an scFv that binds a target antigen;
- an FKBP multimerization domain polypeptide or variant thereof;
- and a CD4 transmembrane domain or an amnionless (AMN) transmembrane domain;
- and
- a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides and the first and third polypeptides.
12 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof, a CD8α transmembrane domain or a CD4 transmembrane domain;
- a CD137 co-stimulatory domain;
- and/or a CD3ζ primary signaling domain;
- (b) a polypeptide cleavage signal;
- and
- (c) a second polypeptide comprising:
- a binding domain that binds to CD33;
- an FKBP multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or a CD8α transmembrane domain.
6 more elements
A fusion polypeptide comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof, a CD8α transmembrane domain or a CD4 transmembrane domain;
- a CD137 co-stimulatory domain;
- and/or a CD3ζ primary signaling domain;
- (b) a polypeptide cleavage signal;
- (c) a second polypeptide comprising:
- a binding domain that binds to CD33;
- an FKBP multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or a CD8α transmembrane domain;
- (d) a second polypeptide cleavage signal;
- and
- (e) a third polypeptide comprising:
- a binding domain that binds to a target antigen;
- an FKBP multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or an amnionless (AMN) transmembrane domain.
10 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof, a CD8α transmembrane domain or a CD4 transmembrane domain;
- a CD137 co-stimulatory domain;
- and/or a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- a binding domain that binds to CD33;
- an FKBP multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or a CD8α transmembrane domain;
- and
- (c) a bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides.
6 more elements
A polypeptide complex comprising:
- (a) a first polypeptide comprising:
- an FRB multimerization domain polypeptide or variant thereof, a CD8α transmembrane domain or a CD4 transmembrane domain;
- a CD137 co-stimulatory domain;
- and/or a CD3ζ primary signaling domain;
- (b) a second polypeptide comprising:
- a binding domain that binds to CD33;
- an FKBP multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or a CD8α transmembrane domain;
- (c) a third polypeptide comprising:
- a binding domain that binds a target antigen;
- an FKBP multimerization domain polypeptide or variant thereof, and a CD4 transmembrane domain or an amnionless (AMN) transmembrane domain;
- and
- (d) a bridging factor associated with and disposed between the multimerization domains of the first polypeptide and the second polypeptide and the first polypeptide and the third polypeptide, when the first polypeptide and the second polypeptide and the third polypeptide are expressed in a cell.
9 more elements
Dependencies are inferred from the claim text.