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Publication Number
US-12060585-B2
Publication Date
2024-08-13
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 disclosed invention relates to recombinant polypeptides defined by amino acid sequence identity to specific SEQ ID NOs. A recombinant polypeptide is provided that comprises an amino acid sequence having at least 90% identity with the sequence of any one of SEQ ID NOs: 57, 73, 77, and 81, and the recombinant polypeptide does not comprise an intracellular signaling domain.
The disclosure also relates to cell tag constructs for engineered immune cells in immunotherapy. It describes polynucleotide/polypeptide cell tag constructs that include truncated variants having a non-immunogenic extracellular domain, including extracellular domains corresponding to HER1, CD20, LNGFR, and CD52, and further includes optional signal peptide and peptide linker features.
The constructs are configured with cell-surface anchoring using transmembrane domains. The transmembrane portion is used for transmembrane dimerization or multimerization to amplify depletion signals upon binding by a predetermined antibody, and the cell tag is described as a depletion/kill tag that enables control of engineered cell activity, including depletion or kill.
The specification further describes functional variants of CAR-related polypeptides and nucleic acids, including co-expression from a single transcript and examples within a CD19-focused CAR-T framework, together with related engineered receptor and expression constructs including engineered TCR and cytokine/tag constructs such as membrane-bound IL-15.
Claims Coverage
The independent claim coverage centers on recombinant polypeptides defined by amino acid sequence identity to specific SEQ ID NOs and the absence of an intracellular signaling domain. Dependent claims refine the covered sequence set, tighten identity thresholds, and further add and restrict a signal peptide by specifying named signal peptide types and an identity constraint relative to SEQ ID NO: 4.
Recombinant polypeptide defined by amino acid sequence identity without intracellular signaling domain
A recombinant polypeptide comprising an amino acid sequence having at least 90% identity with the sequence of any one of SEQ ID NOs: 57, 73, 77, and 81, wherein the recombinant polypeptide does not comprise an intracellular signaling domain.
Tightened sequence identity to selected SEQ ID NOs
A recombinant polypeptide in which the amino acid sequence has at least 99% identity to SEQ ID NOs 73, 77, and 81.
Specified 90% identity to SEQ ID NO: 57
A recombinant polypeptide containing an amino acid sequence having at least 90% identity with the sequence of SEQ ID NO: 57.
Signal peptide inclusion
The recombinant polypeptide further includes a signal peptide.
Signal peptide selected from named types
The signal peptide is selected from GMCSFRα, Ig Kappa, Immunoglobulin E, CD8α, TVB2, CD52, or LNGFR signal peptides.
Tight signal peptide sequence identity to SEQ ID NO: 4
The signal peptide contains an amino acid sequence that is at least 99% identical to SEQ ID NO: 4.
The coverage is centered on recombinant polypeptides defined by amino acid sequence identity to specific SEQ ID NOs, a required lack of an intracellular signaling domain, and optional refinements that add a signal peptide with defined signal peptide selection and sequence identity constraints.
Stated Advantages
Mitigation of toxicities such as cytokine storm and tumor lysis.
Amplification of depletion signals upon binding by a predetermined antibody using transmembrane dimerization or multimerization.
Control of engineered cell activity through depletion or kill tag behavior.
Improved elimination/selectivity when dimerization-domain tags are co-expressed with immune receptors.
Documented Applications
Engineered immune cell immunotherapy using cell tag constructs that function as depletion/kill tags.
Use with CAR/TCR and cytokines in engineered immune cells, including antibody-mediated ADCC and CDC.
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