# US 2025/0154530 A1 · Modified monocytes/macrophages/dendritic cells expressing chimeric antigen receptors and uses in diseases and disorders associated with protein aggregates > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0154530 A1 - Document ID: US20250154530A1 - Status: Published application - Kind: A1 - Application number: 18/809,915 - Filed: 2024-08-20 - Published: 2025-05-15 - Earliest claimed: 2018-02-02 - Assignees: The Trustees of the University of Pennsylvania - Applicants: The Trustees of the University of Pennsylvania - Inventors: Saar Gill; Michael Klichinsky - Web page: https://patentgrep.com/patent/US20250154530A1 ## CPC - C12N 15/87: Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation - A61K 40/17: Monocytes; Macrophages - A61K 40/24: Antigen-presenting cells [APC] - A61K 40/31: Chimeric antigen receptors [CAR] - A61K 40/40: characterised by antigens that are targeted or presented by cells of the immune system - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - C12N 5/0645: {Macrophages, e.g. Kuepfer cells in the liver; Monocytes} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 2239/31: characterized by the route of administration - A61K 2239/38: characterised by the dose, timing or administration schedule - C07K 2319/03: containing a transmembrane segment - C12N 2510/00: Genetically modified cells - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention relates to compositions and methods for treating diseases and/or disorders associated with protein aggregates. By expressing a chimeric antigen receptor (CAR) in a monocyte, macrophage or dendritic cell, the modified cell is recruited or applied to the tissue microenvironment where it acts as a potent immune effector by infiltrating the tissue and eliminating, reducing, inhibiting or preventing protein aggregation. Other aspects of this invention include methods and pharmaceutical compositions comprising the CAR modified monocyte, macrophage or dendritic cell for treating a condition, such as a neurodegenerative disease/disorder, an inflammatory disease/disorder, a cardiovascular disease/disorder, a fibrotic disease/disorder and amyloidosis. ## Claims ### Claim 1 A cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain comprising an antigen binding domain, a transmembrane domain and an intracellular domain, wherein the antigen binding domain binds to an antigen of an amyloid protein, wherein the cell is a monocyte, macrophage and/or a dendritic cell that expresses the CAR, and wherein the cell exhibits phagocytic activity upon binding of the antigen binding domain to the antigen of the amyloid protein. ### Claim 2 A cell comprising a nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the nucleic acid sequence comprises one or more of a nucleic acid sequence encoding an extracellular domain comprising an antigen binding domain, a nucleic acid sequence encoding a transmembrane domain and a nucleic acid sequence encoding an intracellular domain, wherein the antigen binding domain binds to an antigen of an amyloid protein, wherein the cell is a monocyte, macrophage and/or a dendritic cell that expresses the CAR, and wherein the cell exhibits phagocytic activity upon binding of the antigen binding domain to the antigen of the amyloid protein. ### Claim 3 (depends on 1) The cell of claim 1, wherein the antigen binding domain binds to the antigen of the amyloid protein in a tissue of a subject with amyloidosis or an amyloid-associated disorder. ### Claim 4 (depends on 1) The cell of claim 1, wherein the intracellular domain is or comprises at least one of a co-stimulatory molecule and a signaling domain. ### Claim 5 (depends on 1) The cell of claim 1, wherein the antigen binding domain is or comprises an antibody agent. ### Claim 6 (depends on 1) The cell of claim 1, wherein the antigen binding domain is or comprises an antibody agent selected from the group consisting of a monoclonal antibody, polyclonal antibody, synthetic antibody, human antibody, humanized antibody, single domain antibody, single chain variable fragment, and antigen-binding fragments thereof. ### Claim 7 (depends on 1) The cell of claim 1, wherein the antibody agent is or comprises a TDP-43 antibody, a beta-amyloid antibody, an amyloid antibody, and/or an scFV of any of the foregoing antibodies. ### Claim at position 8 8-9. (canceled) ### Claim 10 (depends on 3) The cell of claim 3, wherein the amyloidosis is selected from the group consisting of Primary Amyloidosis (AL), Secondary Amyloidosis (AA), Familial Amyloidosis (A TTR), other Familial Amyloidoses, Beta-2 Microglobulin Amyloidosis, Localized Amyloidosis, Heavy Chain Amyloidosis (AH), Light Chain Amyloidosis (AL), Primary Systemic Amyloidosis, ApoAI Amyloidosis, ApoAII Amyloidosis, ApoAIV Amyloidosis, Apolipoprotein C2 Amyloidosis, Apolipoprotein C3 Amyloidosis, Corneal lactoferrin amyloidosis, Transthyretin-Related Amyloidosis, Dialysis amyloidosis, Fibrinogen amyloidosis, Lect2 amyloidosis (ALECT2), and Lysozyme amyloidosis. ### Claim at position 10 11-12. (canceled) ### Claim 13 (depends on 1) The cell of claim 1, wherein the intracellular domain of the CAR comprises dual signaling domains. ### Claim 14 (depends on 1) The cell of claim 1, wherein the intracellular domain is from a costimulatory molecule selected from the group consisting of TCR, CD3 zeta, CD3 gamma, CD3 delta, CD3 epsilon, CD86, common FcR gamma, FcR beta (Fe Epsilon R1b), CD79a, CD79b, Fcgamma RIIa, DAP10, DAP12, T cell receptor (TCR), CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte functionassociated antigen-I (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, CDS, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), CD127, CD160, CD19, CD4, CD8alpha, CD8beta, IL2R beta, IL2R gamma, IL7R alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, NKp44, NKp30, NKp46, NKG2D, and any combinations thereof. ### Claim 15 (depends on 1) The cell of claim 1, wherein the intracellular domain is or comprises CD3zeta. ### Claim 16 (depends on 1) The cell of claim 1, wherein the cell exhibits one or more activities selected from the group consisting of phagocytosis, targeted cellular cytotoxicity, antigen presentation, and cytokine secretion. ### Claim 17 (depends on 1) The cell of claim 1, further comprising at least one agent selected from the group consisting of a nucleic acid, an antibiotic, an anti-inflammatory agent, an antibody or antibody fragments thereof, a growth factor, a cytokine, an enzyme, a protein, a peptide, a fusion protein, a synthetic molecule, an organic molecule, a carbohydrate, a lipid, a hormone, a microsome, and any combinations thereof. ### Claim 18 (depends on 1) The cell of claim 1, wherein an activity of the cell is enhanced by inhibition of CD47 and/or SIRPa activity. ### Claim 19 (depends on 1) A pharmaceutical composition comprising the cell of claim 1, and a pharmaceutically acceptable carrier. ### Claim 20 (depends on 19) The pharmaceutical composition of claim 19, further comprising at least one agent selected from the group consisting of a nucleic acid, an antibiotic, an anti-inflammatory agent, an antibody or antibody fragments thereof, a growth factor, a cytokine, an enzyme, a protein, a peptide, a fusion protein, a synthetic molecule, an organic molecule, a carbohydrate, a lipid, a hormone, a microsome, and any combinations thereof. ### Claim 21 (canceled) ### Claim 22 (depends on 19) A method of treating amyloidosis or an amyloid-associated disorder in a subject in need thereof, or stimulating an immune response to a target cell or tissue in a subject suffering from amyloidosis or an amyloid-associated disorder, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 19. ### Claim 23 (canceled) ### Claim 24 A method of modifying a cell, the method comprising introducing into a monocyte, macrophage and/or dendritic cell a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular domain comprising an antigen binding domain, a transmembrane domain and an intracellular domain, wherein the antigen binding domain binds to an antigen of an amyloid protein. ### Claim 25 (depends on 24) The method of claim 24, wherein introducing the CAR into the cell comprises introducing a nucleic acid sequence encoding the CAR into the cell. ### Claim at position 24 26-36. (canceled) ### Claim 37 (depends on 24) A composition comprising a cell made by the method of claim 24.