CD33 specific chimeric antigen receptors
Inventors
Shah, Rutul • Chan, Tim • Emtage, Peter • Yarlagadda, Ramya
Assignees
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Publication Number
US-12559536-B2
Publication Date
2026-02-24
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 invention relates to a vector comprising a backbone and a nucleic acid sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO: 36 or 56. The vector further encodes a chimeric antigen receptor (CAR) that includes a CD33 antigen-binding domain, a transmembrane domain, and an intracellular signaling domain, with the CD33 antigen-binding domain comprising one of several specified pairs of polypeptides based on particular amino acid sequences.
The CAR architecture includes defined transmembrane and intracellular signaling components, including CD3z signaling. Costimulatory domains are discussed as part of the engineered CAR signaling components, with example costimulation indicated by 4-1BB or CD28, and the disclosed compositions define CD33 binding together with intracellular signaling components to create a functional CAR polypeptide.
The disclosed system also includes optional safety or kill-switch related components using a truncated epidermal growth factor receptor (EGFR), referred to as HER1t or HER1t-1, and/or an additional antigen as a kill/safety tag such as CD20. In this context, truncated EGFR is described as enabling depletion using cetuximab, and CD20 as enabling depletion using rituximab. The treatment setting discussed is relapsed/refractory AML and other proliferative disorders, and the engineered nucleic acid is provided in vector formats including lentiviral, retroviral, and non-viral vectors such as Sleeping Beauty transposons.
Claims Coverage
The document contains one independent claim directed to a vector encoding a specific CD33 CAR polypeptide and defined CAR components, with dependent claims further constraining the allowable CD33 antigen-binding domain sequence pairs, vector type and expression elements, and sequence-identity constraints for CAR subdomains.
Vector encoding a CD33 CAR with defined antigen-binding domain pairs
A vector comprising a backbone and a nucleic acid sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO: 36 or 56, and a chimeric antigen receptor (CAR) comprising a CD33 antigen-binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the CD33 antigen binding domain comprises either 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 SEQ ID NO: 13 and SEQ ID NO: 14.
Vector includes lentiviral, retroviral, or non-viral vector type
The vector is a lentiviral vector, a retroviral vector, or a non-viral vector.
Vector includes an hEF1a1 promoter
The vector further includes an hEF1a1 promoter.
CAR stalk and intracellular signaling domains with sequence-identity constraints
The claim defines a CAR vector that includes a stalk domain and specified intracellular signaling domains, where each domain polypeptide has at least 90% identity to particular SEQ ID NO sequences.
Immune effector cell subtype
The immune effector cell is a T cell, a Natural Killer (NK) cell, a cytotoxic T lymphocyte (CTL), or a regulatory T cell.
Overall claim coverage centers on a CAR vector targeting CD33 with defined CD33 antigen-binding domain composition based on specified SEQ ID NO pairings, and further refines the vector and CAR implementation by specifying permissible vector types, a named expression promoter element, and sequence-identity constraints for CAR domains, with dependent coverage extending to immune effector cell subtypes that can carry the vector.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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