Chimeric antigen receptor system with adaptable receptor specificity
Inventors
CARTON, Jill Marinari • NASO, Michael Francis • BORGES, Luis Ghira • Wheeler, John • Devaney, Andrew
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11883432-B2
Publication Date
2024-01-30
Expiration Date
Abstract
The present disclosure provides chimeric antigen receptors (CARs), particularly CARs that have adaptable receptor specificity (arCARs). Also provided are polypeptides of the CARs and other related molecules, polynucleotides, vectors, and cell compositions comprising the same. Pharmaceutical compositions comprising the polypeptides, polynucleotides, vectors, or cells of the present disclosure, and their uses in treating a disease in a subject are also provided.
Core Innovation
The invention relates to a universal chimeric antigen receptor system having an adaptable receptor specificity component (arCAR). The system includes an immune effector cell carrying a chimeric antigen receptor comprising a first polypeptide with an extracellular tag-binding domain, a transmembrane domain, and at least one intracellular signaling domain, and a second soluble polypeptide comprising an antigen-binding domain that binds an antigen on a target cell and a tag recognized by the extracellular tag-binding domain.
The universal arCAR platform is configured through a matched universal tag/anti-tag interaction. The tag is defined by polypeptide sequences and is paired with an extracellular tag-binding domain defined by corresponding polypeptide sequences, with the sequences set such that either the tag comprises SEQ ID NO: 112 and the extracellular tag-binding domain comprises SEQ ID NO: 129, or the tag comprises SEQ ID NO: 129 and the extracellular tag-binding domain comprises SEQ ID NO: 112.
The document further describes antigen-binding domain formats including antibody, antigen-binding fragments, scFv derived from antibodies or CAR-derived binders, and alternative binding components including non-immunoglobulin scaffold types and VHH tags derived from non-human sources such as anti-idiotype VHH binders. It also describes additional configurations including multiple arCARs with unique tag/tag-binding pairs, polynucleotides, vectors, and modified host cells expressing the first and/or second arCAR polypeptides.
Applications described include treatment concepts using immune effector cells together with soluble tag polypeptides or encoded host cells producing the second soluble polypeptide. Immune effector cell types described include T cells and NK cells, including iPSC-derived T/NK cells, and the treatment concepts are directed to cancers and autoimmune disorders.
Claims Coverage
The independent claim defines a universal arCAR system with an adaptable receptor specificity component, centered on a two-component receptor architecture and two defined sequence pairing options for the tag and extracellular tag-binding domain.
Universal arCAR system with adaptable receptor specificity component
An immune effector cell having a chimeric antigen receptor comprising a first polypeptide with an extracellular tag-binding domain, a transmembrane domain, and at least one intracellular signaling domain, and a second soluble polypeptide with an antigen-binding domain that binds an antigen on a target cell and a tag recognized by the extracellular tag-binding domain.
Defined universal tag and extracellular tag-binding domain sequence pairing
A configuration in which the tag comprises the polypeptide sequence of SEQ ID NO: 112 and the extracellular tag-binding domain comprises the polypeptide sequence of SEQ ID NO: 129, or alternatively the tag comprises the polypeptide sequence of SEQ ID NO: 129 and the extracellular tag-binding domain comprises the polypeptide sequence of SEQ ID NO: 112.
Antigen-binding domain scaffold selection for the second polypeptide
The antigen-binding domain is an antibody, an antigen-binding fragment thereof, scFv derived from antibodies or CAR-derived binders, or an alternative scaffold.
Multiple arCARs with unique tag/tag-binding pairs
Multiple arCARs with unique tag/tag-binding pairs.
Modified host cells expressing arCAR polypeptides
Modified host cells expressing the first and/or second arCAR polypeptides.
iPSC-derived immune effector cell configuration
The immune effector cell is a T cell or NK cell derived from an induced pluripotent stem cell (iPSC).
Constitutive expression of the first polypeptide in the immune effector cell
The immune effector cell constitutively expresses the first polypeptide.
Therapeutic treatment administration with arCAR components
A method for treating a disease in a subject administers a therapeutically effective amount of an immune effector cell engineered with a chimeric antigen receptor together with the second polypeptide, encoded polynucleotide, or a host cell producing the second soluble polypeptide of the arCAR system.
The claim coverage centers on an arCAR architecture that separates immune effector signaling from adaptable antigen recognition through a soluble polypeptide, with universality anchored by defined sequence pairings between the tag and the extracellular tag-binding domain and with additional refinements for scaffold choice, cell sourcing, expression, and treatment administration formats.
Stated Advantages
High specificity associated with the universal tag/anti-tag interaction approach.
Reduced off-target binding associated with the universal tag/anti-tag interaction approach.
Affinity tunability associated with the universal tag/anti-tag interaction approach.
Platform-agnostic scaffold swapping associated with the universal universal CAR concept.
Ability to generate many CAR/tag pairs associated with the universal tag/anti-tag interaction approach.
Fit-for-purpose therapy associated with the universal CAR platform.
Documented Applications
Treatment concepts for cancers using immune effector cells together with soluble tag polypeptides or encoded host cells producing the second soluble polypeptide.
Treatment concepts for autoimmune disorders using immune effector cells together with soluble tag polypeptides or encoded host cells producing the second soluble polypeptide.
Use of iPSC-derived T/NK cells as immune effector cell types within the arCAR system for cancer and autoimmune disorder treatment concepts.
Interested in licensing this patent?