Compositions and methods for treatment of cancer
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Publication Number
US-10669349-B2
Publication Date
2020-06-02
Expiration Date
Abstract
Compositions, e.g., compositions comprising cellular therapeutics and/or protein therapeutics, and methods of using such compositions for treating cancer are described.
Core Innovation
The invention relates to fusion proteins and engineered adoptive immune cell therapeutics for cancer treatment, using antigen-binding receptor signaling to control therapeutic expression. An antigen-binding receptor includes an antigen-binding domain, a transmembrane domain, and a cytosolic signaling domain that activates an inducible promoter, and the inducible promoter drives expression of therapeutic genes or proteins in the context of tumor cells.
A central architecture is redirected immune activity coupled to conditional expression, where signaling through the antigen-binding receptor controls therapeutic outputs on or near tumor cells. The disclosure discusses antigen decoration strategies using inducible scFv-CD19 or inducible scFv-EGFR fusion proteins to enable redirected killing by additional CAR-T or targeting therapeutics, and also describes tunable signaling domains intended to activation, proliferation, or survival while avoiding triggering cytotoxicity.
The disclosure also includes inducible expression constructs for therapeutic components such as inducible cytokines and an inducible toxin smart bomb concept with safety switches. Masked, Probody-like antigen-binding constructs are described to regulate binding to reduce off-tumor activity, and scaffold and fusion protein strategies are discussed, including CD19 as a scaffold for CD19 variants and Fc-based fusion constructs, including CD19-scFv-Fc and Fc Ig swap or loop variants.
Claims Coverage
Independent claim coverage centers on a CD19 extracellular-domain fusion protein that links tumor-antigen binding to an FMC63-recognized CD19 epitope. The coverage further specifies antigen-binding fragment format, binding context, and selected tumor antigen options.
FMC63-recognized CD19 extracellular epitope fusion
A fusion protein comprising an antibody or antigen-binding fragment that binds a tumor antigen and an extracellular domain of CD19, or a fragment thereof, that includes an epitope recognized by anti-CD19 antibody FMC63.
Defined antigen-binding fragment formats for the tumor antigen binder
The antigen-binding fragment is an Fab, scFv, Fv, or VHH.
CD19 extracellular domain binds a cellular therapeutic
The extracellular domain or fragment of CD19 binds a cellular therapeutic.
CD19 extracellular domain binds an antibody-drug conjugate
The extracellular domain or fragment of CD19 binds an antibody-drug conjugate.
Selected tumor antigen alternatives
The tumor antigen is selected from HER-2/neu, c-met, EGFR, Ga733/EpCAM, CD20, ROR1, CLL-1/CLECK12A, or BCMA.
The claims focus on a fusion protein coupling tumor-antigen binding to a CD19 extracellular domain containing an FMC63-recognized epitope, with further limitation to specific antigen-binding fragment formats, alternative CD19 extracellular binding targets, and selected tumor antigen options.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Cancer treatment using adoptive immune cell therapeutics and engineered fusion protein strategies that control therapeutic expression via antigen-binding receptor signaling.
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