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Publication Number
US-11718929-B2
Publication Date
2023-08-08
Expiration Date
Abstract
The present invention relates generally to the field of making novel antigen binding domains against infectious diseases. The present invention also relates to novel CARs that utilize the novel antigen binding domains as an extracellular element. The present invention also relates to use of the novel antigen binding domains as therapeutic agents.
Core Innovation
The invention provides methods for generating novel CAR extracellular antigen-binding domains from subject immune repertoires. The subject repertoire sources include antibody B-cell repertoires and single-chain antibodies, T-cell receptor repertoires, and innate receptor families, and the generated antigen-binding domains are engineered into a CAR chassis.
The invention further describes CAR chassis architectures including Smart-CAR, DE-CAR, Smart-DE-CAR, and Side-CAR. These architectures include controllable expression using destabilizing elements and RNA control devices based on aptamer, ribozyme, riboswitch, and a theophylline-responsive switch, with elements such as ecDHFR and NFAT reporter/control region functionality to provide controllable expression and effector activity.
The invention includes validating and identifying target antigens and using engineered eukaryotic, especially immune, cells for therapeutic applications. The described applications include infectious diseases, cancers, autoimmune disorders, and senescent cells.
Claims Coverage
The partial claim set includes one independent claim covering a nucleic-acid set that encodes multiple subject-derived antigen binding domains fused to a CAR chassis, with the CAR chassis including a transmembrane element and an intracellular element containing a T cell receptor zeta chain and a costimulatory molecule. The independent claim contains 3 inventive features.
Multiple subject-derived antigen binding domains fused to CAR chassis
A plurality of nucleic acids comprising polynucleotides encoding a plurality of different antigen binding domains derived from a subject having an immune response to a cancer, where each polynucleotide encodes a fusion polypeptide comprising the antigen binding domain fused to a CAR chassis.
CAR chassis with transmembrane element and intracellular TCR zeta plus costimulatory
The CAR chassis is comprised of a transmembrane element and an intracellular element comprising a T cell receptor zeta chain and a costimulatory molecule, where the transmembrane element is fused to the intracellular element and the costimulatory molecule is fused to the intracellular element.
Costimulatory molecule selected as CD137, CD27 or CD28
The costimulatory molecule is CD137, CD27 or CD28.
Across the independent claim, the inventive scope is directed to a nucleic-acid plurality that encodes multiple distinct subject-derived antigen binding domains fused to a CAR chassis. The CAR chassis includes a transmembrane element fused to an intracellular element containing a T cell receptor zeta chain together with a costimulatory molecule, specifically CD137, CD27 or CD28.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Therapeutic applications against infectious diseases.
Therapeutic applications against cancers.
Therapeutic applications against autoimmune disorders.
Therapeutic applications against senescent cells.
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