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Publication Number
US-12180517-B2
Publication Date
2024-12-31
Expiration Date
Abstract
Disclosed herein are polynucleotides encoding cell tags for use in immunotherapeutic applications, and systems comprising polynucleotide cell tags for regulating the activity of a cell. The compositions, methods and systems described herein provide tools for regulating activity of genetically engineered cells in a subject.
Core Innovation
The invention relates to treating cancer in a subject using engineered effector cells. The engineered effector cells express a chimeric antigen receptor (CAR) that specifically binds an antigen selected from CD19, CD20, CD33, BCMA, CD123, EGFRvIII, ROR1, HER2, GD2, mesothelin, CD22, and MUC-16, and the cancer is associated with overexpression of the selected antigen. The method includes administering a binding partner selected from cetuximab, panitumumab, and functional fragments thereof.
The patent describes cell tag polypeptide constructs and encoding polynucleotides for immunotherapy. The constructs include truncated non-immunogenic HER1 polypeptides fused to a signal peptide and a transmembrane domain, with sequence identity relationships to defined SEQ ID NOs for the truncated extracellular region and the transmembrane region.
The constructs further include a transmembrane dimerization domain that pre-dimerizes the tag at the cell surface. The patent links this dimerization to amplification of antibody-mediated depletion signals, including ADCC and CDC, and describes optional peptide linkers and different dimerization approaches, including homodimer and heterodimer arrangements, with covalent and noncovalent dimerization options.
The patent also describes administering engineered T or NK cells that express these cell tag polypeptides alongside immunotherapeutic binding partner antibodies. A predetermined binding partner is administered to achieve controlled downregulation or kill switching, and the patent frames this as providing enrichment or monitoring with engineered cells, including CAR/TCR-expressing cells. The binding partners explicitly include rituximab, cetuximab, panitumumab, and alemtuzumab, and functional fragments thereof.
Claims Coverage
The independent claim coverage centers on a cancer-treatment method that administers CAR-expressing engineered effector cells targeting antigens associated with overexpression, together with a binding partner selected from cetuximab or panitumumab, or functional fragments. The engineered effector cells are further defined by a recombinant polypeptide that includes a truncated non-immunogenic HER1 polypeptide and a specified transmembrane domain defined by sequence identity to listed SEQ ID NOs. Multiple dependent claims add further identity constraints and functional components, including IL-15/IL-15Rα and Sleeping Beauty transposase.
CAR-expressing engineered effector cells for overexpressed antigens
Administering an engineered effector cell expressing a chimeric antigen receptor (CAR) that specifically binds to an antigen selected from CD19, CD20, CD33, BCMA, CD123, EGFRvIII, ROR1, HER2, GD2, mesothelin, CD22, and MUC-16, wherein the cancer is associated with overexpression of the antigen.
Co-administration of cetuximab/panitumumab binding partner
Administering a binding partner selected from cetuximab, panitumumab, and functional fragments thereof together with the engineered effector cell.
Truncated non-immunogenic HER1 polypeptide and defined transmembrane domain in the recombinant polypeptide
The engineered effector cell comprises a recombinant polypeptide comprising a truncated non-immunogenic HER1 polypeptide consisting of an amino acid sequence having at least 90% identity with SEQ ID NO: 200 and an amino acid sequence having at least 90% identity with any one of SEQ ID NOs: 203-209, and a transmembrane domain comprising an amino acid sequence having at least 90% identity with any one of SEQ ID NOs: 26, 28, 30, 32, 34, 36, 38, and 40.
Overall, the claim coverage defines a cancer-treatment method based on administering an engineered CAR effector cell and a specified antibody binding partner, while structurally defining a recombinant polypeptide that includes a truncated non-immunogenic HER1 extracellular component and a transmembrane domain using specified SEQ ID NOs and at least 90% identity thresholds.
Stated Advantages
Amplification of antibody-mediated depletion signals including ADCC and CDC.
Documented Applications
Treating cancer in a subject in need thereof by administering engineered effector cells expressing a CAR that binds antigens associated with overexpression, together with a binding partner selected from cetuximab, panitumumab, and functional fragments.
Enrichment or monitoring with engineered cells, including CAR/TCR-expressing cells.
Controlled downregulation or kill switching.
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