CD33 specific chimeric antigen receptors
Inventors
Shah, Rutul • Chan, Tim • Emtage, Peter • Yarlagadda, Ramya
Assignees
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Publication Number
US-11787848-B2
Publication Date
2023-10-17
Expiration Date
Abstract
Provided herein are chimeric antigen receptors (CARs) for cancer therapy, and more particularly, CARs containing a scFv from a CD33 monoclonal antibody. Provided are immune effector cells containing such CARs, and methods of treating proliferative disorders such as acute myeloid leukemia (AML), and relapsed or refractory AML.
Core Innovation
The disclosure provides a vector comprising a backbone and a nucleic acid sequence encoding a cell tag and a chimeric antigen receptor (CAR). The cell tag comprises an amino acid sequence having at least 95% identity with the full length of SEQ ID NO: 54, and the CAR includes a CD33 antigen binding domain, a stalk domain, a transmembrane domain, a costimulatory signaling domain, and a CD3 zeta signaling domain.
The CD33 antigen binding domain is defined by selected amino acid sequence combinations, including pairs of SEQ ID NO: 1 and SEQ ID NO: 3, SEQ ID NO: 9 and SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, or the full length of SEQ ID NO: 13 together with SEQ ID NO: 14. The stalk domain is selected from IgG1 hinge, IgG4 hinge, the CH2CH3 region of immunoglobulin, or the CD8alpha hinge domain, and the transmembrane domain is selected from specified T-cell receptor and immune receptor transmembrane regions or a synthetic predominantly hydrophobic transmembrane domain.
The costimulatory signaling domain is defined as 4-1BB, CD28, or both, together with a CD3 zeta signaling domain. The disclosed systems are used with engineered immune effector cells including T cells and/or NK/CTL/Tregs, and therapeutic use is described for acute myeloid leukemia (AML), including relapsed or refractory AML.
Claims Coverage
The independent claims provided include one independent claim. It covers a vector that encodes a cell tag sequence with an identity constraint and a CD33 CAR with defined subdomain options for the CD33 binding domain, stalk, transmembrane, costimulatory signaling, and CD3 zeta.
Cell tag with identity constraint
A cell tag comprising an amino acid sequence having at least 95% identity with the full length of SEQ ID NO: 54.
Defined CD33 antigen binding domain sequences
A CD33 antigen binding domain comprising amino acid sequence options selected from SEQ ID NO: 1 and SEQ ID NO: 3; SEQ ID NO: 9 and SEQ ID NO: 10; SEQ ID NO: 11 and SEQ ID NO: 12; or the full length of SEQ ID NO: 13 and SEQ ID NO: 14.
Ig-derived or CD8alpha stalk domain options
A stalk domain comprising a hinge region from IgG1, a hinge region from IgG4, the CH2CH3 region of immunoglobulin, or the CD8alpha hinge domain.
Transmembrane domain selection
A transmembrane domain comprising the transmembrane region of an enumerated set of proteins or a synthetic predominantly hydrophobic transmembrane region.
4-1BB and/or CD28 costimulatory signaling plus CD3 zeta
A costimulatory signaling domain comprising 4-1BB, CD28, or both, together with a CD3 zeta signaling domain.
The claim coverage centers on a single vector design that combines a defined cell tag with a CD33 CAR whose key subdomains are restricted to specific sequence- or domain-based options.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Therapeutic use in acute myeloid leukemia (AML), including relapsed or refractory AML.
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