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Publication Number
US-11118168-B2
Publication Date
2021-09-14
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 describes a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 57. The polypeptide includes a truncated non-immunogenic HER1 polypeptide comprising a HER1 Domain III and a truncated HER1 Domain IV, together with a non-HER1 transmembrane domain and a peptide linker that links the HER1 polypeptide to the non-HER1 transmembrane domain.
The disclosed structure is also presented as a polypeptide comprising the amino acid sequence of SEQ ID NO: 57. The patent describes embodiments as engineered truncated cell tags and next-generation multimerizing HER1t cell tags using anti-HER1 antibodies, and dependent claim elements narrow the HER1 polypeptide to binding to an anti-HER1 antibody selected from a defined panel of therapeutic antibodies.
The document ties the disclosed HER1t truncations and linked transmembrane architecture to antibody-mediated effector functionality. It describes expression and antibody-specific ADCC and CDC functionality, targetable depletion via ADCC/CDC, and conditional control of therapeutic output, and associates these engineered-cell systems with immunotherapy contexts.
Claims Coverage
The document contains two independent claims covering complementary embodiments: a polynucleotide encoding the defined SEQ ID NO: 57 HER1-based construct and a polypeptide comprising the amino acid sequence of SEQ ID NO: 57. Across the independent claims, there are 2 main inventive features: the truncated non-immunogenic HER1 architecture and the fusion architecture to a non-HER1 transmembrane domain via a peptide linker.
Polynucleotide encoding SEQ ID NO: 57 cell-tag fusion
A polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 57, wherein the polypeptide comprises a truncated non-immunogenic HER1 polypeptide comprising a HER1 Domain III and a truncated HER1 Domain IV, a non-HER1 transmembrane domain, and a peptide linker linking the HER1 polypeptide to the non-HER1 transmembrane domain.
Polypeptide with SEQ ID NO: 57 cell-tag fusion
A polypeptide comprising the amino acid sequence of SEQ ID NO: 57, wherein the polypeptide comprises a truncated non-immunogenic HER1 polypeptide comprising a HER1 Domain III and a truncated HER1 Domain IV, a non-HER1 transmembrane domain, and a peptide linker linking the HER1 polypeptide to the non-HER1 transmembrane domain.
Anti-HER1 antibody binding to a defined therapeutic antibody panel
The polynucleotide or polypeptide wherein said HER1 polypeptide binds to an anti-HER1 antibody selected from cetuximab, futuximab, depatuxizumab, imgatuzumab, laprituximab, matuzumab, necitumumab, nimotuzumab, panitumumab, or zalutumumab.
Across both independent claims, the core claim coverage is the SEQ ID NO: 57-defined truncated non-immunogenic HER1 Domain III/Domain IV construct linked through a peptide linker to a non-HER1 transmembrane domain. Dependent claims further narrow the functional scope to binding an anti-HER1 antibody selected from a specified panel, and one dependent claim specifies inclusion of a particular encoding polynucleotide sequence.
Stated Advantages
Provides antibody-specific ADCC and CDC functionality using next-generation multimerizing HER1t cell tags with anti-HER1 antibodies such as cetuximab.
Reports improved ADCC with dimerizing TM-A versions and qualitatively indicates specific ADCC outcomes in certain assays.
Conditional control of therapeutic output via antibody targeting and depletion mechanisms (ADCC/CDC) is described in the document.
Mitigation of cytokine storm and tumor lysis is described in the document.
Documented Applications
Use as engineered truncated cell tags and next-generation multimerizing HER1t cell tags that enable antibody-mediated ADCC/CDC functionality with anti-HER1 antibodies.
Engineered-cell immunotherapy contexts are described, including integration with engineered immune cells and therapeutic output control using antibody-targetable cell tags.
The document describes depletion induction via predetermined antibodies through ADCC/CDC as part of immunotherapy control.
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