Chimeric antigen receptor with single domain antibody
Inventors
MCGUINNESS, Brian • Johnston, Colette
Assignees
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Publication Number
US-11866510-B2
Publication Date
2024-01-09
Expiration Date
Abstract
The invention relates to chimeric antigen receptors (CAR) that comprise one or more single human variable domain antibody and cells that express such CAR. In particular, the invention relates to CARs that include multiple single human variable domain antibodies. In a particular embodiment, the one or more single human variable domain antibody binds to prostate membrane antigen.
Core Innovation
The document describes an isolated chimeric antigen receptor (CAR) for adoptive cellular therapy (ACT) that includes an antigen binding domain, a transmembrane domain, and an intracellular signalling domain. The antigen binding domain comprises a first single human variable heavy chain (V_H) domain antibody and a second single human variable heavy chain (V_H) domain antibody, and the first single human V_H domain antibody comprises SEQ ID NO. 23 or 24 and binds human prostate-specific membrane antigen (PSMA), while the second single human V_H domain antibody binds a second target.
In embodiments directed to PSMA targeting, the binding domain uses two single human V_H domain antibodies such that either only the first V_H domain binds PSMA, with the second V_H binding a second target, or both V_H domains bind human PSMA. The second target can be a tumour antigen or an immuno checkpoint target, and the document provides examples of possible second-target antigens and proteins.
The CAR architecture includes a hinge/spacer, a transmembrane domain, and intracellular signalling domains including CD28 and/or 4-1BB (CD137) together with CD3ζ. The document also describes nucleic acids/vectors, isolated cells, and pharmaceutical compositions comprising the CAR, and includes example testing of PSMA-specific CAR activation using single-V_H and dual-V_H (bispecific/biparatopic) PSMA CAR constructs.
Claims Coverage
The partial claim set provides coverage for two independent CAR formulations. Across these independent claims, the inventive features focus on CARs whose antigen binding domain uses single human variable heavy chain (V_H) domain antibodies with specified SEQ ID NO. 23 or 24 and binding to human PSMA, with one independent claim additionally requiring that the second V_H domain binds a second target.
Two single human V_H domains with PSMA and a second target
An isolated CAR comprising an antigen binding domain, a transmembrane domain and an intracellular signalling domain, wherein the binding domain comprises a first single human V_H domain antibody that comprises SEQ ID NO. 23 or 24, and a second single human V_H domain antibody, wherein the first single human V_H domain antibody binds to human PSMA and the second single human V_H domain antibody binds to a second target.
Two SEQ ID NO. 23/24 V_H domains binding PSMA
An isolated CAR comprising an antigen binding domain, a transmembrane domain and an intracellular signaling domain, wherein the binding domain comprises a first single human V_H domain antibody that comprises SEQ ID NO. 23 or 24 and a second single human V_H domain antibody that comprises SEQ ID NO. 23 or 24, wherein the first and second single human V_H domain antibodies bind to human PSMA.
The claim coverage centers on CARs defined by single human V_H domain antibodies with SEQ ID NO. 23 or 24, configured to bind human PSMA. One independent claim further requires that the second V_H domain binds a second target, including options characterized as a tumour antigen or an immuno checkpoint target.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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