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Publication Number
US-11382965-B2
Publication Date
2022-07-12
Expiration Date
Abstract
The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.
Core Innovation
The document describes chimeric antigen receptor (CAR) constructs directed to BCMA (CD269/TNFRSF17). The CAR architecture includes an anti-BCMA antigen binding fragment and a CAR extracellular domain with hinge/spacer/transmembrane elements, followed by an intracellular signaling domain and co-stimulatory domains selected from CD28, CD134, and CD137.
The CAR constructs are defined in terms of an amino acid sequence region, including CAR amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9. The document further describes polynucleotides and vectors encoding the CAR, including immune effector cell embodiments such as CAR T cells and genetically modified immune effector cells.
It also outlines use of PI3K-pathway inhibitors during T cell activation/expansion to enrich for developmentally potent phenotypes defined by cell phenotype markers including CD62L, CD127, CD197, and CD38. The document describes engineering artificial antigen presenting cells (artificial APCs or aAPCs) to support immune effector cell activation, co-stimulation, and expansion, and includes therapeutic method framing for CAR T targeting BCMA+ B cell malignancies with long-term in vivo persistence.
Claims Coverage
The independent claim set covers sequence-defined CAR, polynucleotide, and vector embodiments, with inventive features centered on CAR amino acids 22-493 of SEQ ID NO: 9. Dependent claim language further narrows the constructs into immune effector cell contexts, including T lymphocytes, NK cells, and human T lymphocytes, and includes composition embodiments with a physiologically acceptable excipient.
Sequence-defined chimeric antigen receptor comprising amino acids 22-493 of SEQ ID NO: 9
A chimeric antigen receptor (CAR) comprising amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
Polynucleotide encoding sequence-defined CAR
A polynucleotide encoding a CAR comprising amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
Vector comprising polynucleotide encoding sequence-defined CAR
A vector comprising a polynucleotide encoding a CAR comprising amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
Immune effector cell expression and composition
An immune effector cell that includes or expresses the CAR, polynucleotide, or vector described, where the immune effector cell is selected from T lymphocytes or natural killer (NK) cells and the immune effector cell can be included in a composition with a physiologically acceptable excipient, including embodiments specifying a human T lymphocyte.
Overall claim coverage is grounded in CARs defined by CAR amino acids 22-493 of SEQ ID NO: 9, with parallel protection for a corresponding polynucleotide and a vector comprising that polynucleotide. Dependent claim language further focuses the constructs into immune effector cell embodiments, including T lymphocytes or NK cells, and composition embodiments including a physiologically acceptable excipient.
Stated Advantages
Supports ex vivo expansion and maintenance of CD28 on CD8 T cells.
Supports ex vivo expansion and maintenance without exogenous cytokines.
Provides long-term in vivo persistence for CAR T targeting BCMA+ B cell malignancies.
Enriches for developmentally potent phenotypes defined by cell phenotype markers including CD62L, CD127, CD197, and CD38.
Documented Applications
Therapeutic administration using CAR T targeting BCMA+ B cell malignancies.
Multiple myeloma and non-Hodgkin lymphoma application context via BCMA-expressing B cells.
Therapeutic conditions for treating B cell malignancies and autoimmune conditions.
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