Therapeutic constructs for treating cancer
Inventors
Ullman, Christopher • Carrington, Christine Anne
Assignees
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Publication Number
US-12233135-B2
Publication Date
2025-02-25
Expiration Date
Abstract
The present disclosure provides nucleic acid constructs for the treatment of cancer, comprising a cancer-specific promoter and one or more therapeutic genes.
Core Innovation
The invention relates to a nucleic acid construct for the treatment of cancer that includes an expression cassette with a cancer-specific promoter and nucleic acid sequences encoding one or more tumor antigens. The tumor-antigen encoding nucleic acid sequences are engineered to have reduced CpG content compared to their wild-type counterparts, and the nucleic acid construct comprises a CpG-free plasmid backbone, or a combination of reduced CpG content and a CpG-free plasmid backbone.
The constructs are configured with a cancer-specific promoter, including PEG-3 and functional derivatives, to drive expression. The tumor antigen sequences can be arranged in multi-gene cassettes using picornavirus 2A ribosome skipping sequences, including P2A or T2A, and can include optional linkage features such as furin cleavage and a GSG linker.
The nucleic acid constructs are described as CpG-free plasmid nanoparticles formulated for systemic delivery using cationic polymers such as linear polyethylenimine. The document also describes cancer therapeutic gene payloads associated with the constructs, including cytokines, thymidine kinase, toxins, PAMP/DAMP, and immune checkpoint inhibitor gene products.
The document further describes antigen-oriented cassette concepts, including promiscuous MHC II epitopes, and combination approaches involving monoclonal antibodies or CAR T-cells. The overall approach addresses cancer treatment by combining cancer-specific promoter-driven tumor antigen expression with engineered reduced CpG content and CpG-free plasmid backbone formulations.
Claims Coverage
The provided content lists one independent claim focused on a cancer treatment nucleic acid construct, with multiple inventive features covering promoter selection, reduced CpG content, plasmid backbone composition, multi-antigen arrangement, and immune checkpoint inhibitor payloads.
Cancer-specific promoter-driven tumor antigen expression with reduced CpG content
A nucleic acid construct for the treatment of cancer comprising an expression cassette with a cancer-specific promoter and nucleic acid sequences encoding one or more tumor antigens, wherein the nucleic acid sequences encoding the one or more tumor antigens are engineered to have a reduced CpG content compared to their wild-type counterparts.
CpG-free plasmid backbone for cancer treatment nucleic acid constructs
A nucleic acid construct for the treatment of cancer comprising an expression cassette, wherein the nucleic acid construct comprises a CpG-free plasmid backbone, or a combination with reduced CpG content tumor-antigen encoding nucleic acid sequences.
PEG-3 promoter or functional derivative
The expression cassette uses a cancer-specific promoter that comprises the PEG-3 promoter or a functional derivative of it.
Multi-tumor-antigen expression using picornavirus 2A ribosome skipping sequences
The nucleic acid sequences encoding the one or more tumor antigens are arranged to be separated using a picornavirus 2A ribosome skipping sequence, optionally specified as P2A or T2A.
Immune checkpoint inhibitor gene encoding monoclonal antibody modalities
The construct includes an immune checkpoint inhibitor gene wherein the immune checkpoint inhibitor gene encodes a monoclonal antibody selected from anti-PD-1, anti-PD-L1, or anti-CTLA-4, optionally including a PD-1 fusion protein comprising PD-1 and an immunoglobulin Fc region.
The inventive coverage centers on cancer-specific promoter-driven expression of tumor antigens with engineered reduced CpG content and, optionally or in combination, a CpG-free plasmid backbone. Additional coverage includes PEG-3 promoter use, multi-antigen cassette arrangement using picornavirus 2A ribosome skipping sequences, and immune checkpoint inhibitor payload modalities such as anti-PD-1, anti-PD-L1, anti-CTLA-4, or PD-1–Fc fusions.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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