# US 11,306,133 B2 · Modified monocytes/macrophage expressing chimeric antigen receptors and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,306,133 B2 - Document ID: US11306133B2 - Status: Granted - Kind: B2 - Application number: 16/858,183 - Filed: 2020-04-24 - Published: 2020-08-06 - Granted: 2022-04-19 - Earliest claimed: 2015-07-28 - Assignees: The Trustees of the University of Pennsylvania - Applicants: The Trustees of the University of Pennsylvania - Inventors: Saar Gill; Michael Klichinsky; Carl H. June - Web page: https://patentgrep.com/patent/US11306133B2 ## CPC - C07K 14/70517: {CD8} - A61K 40/17: Monocytes; Macrophages - A61K 40/31: Chimeric antigen receptors [CAR] - A61K 40/4205: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4} - A61K 40/4211: {CD19 or B4} - A61K 40/4255: {Mesothelin [MSLN]} - A61P 37/02: Immunomodulators - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - C07K 14/70535: {Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)} - C07K 14/7056: {Lectin superfamily, e.g. CD23, CD72} - C07K 16/2803: {against the immunoglobulin superfamily} - C07K 16/30: from tumour cells - C07K 16/32: against translation products of oncogenes - C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} - C12N 5/0645: {Macrophages, e.g. Kuepfer cells in the liver; Monocytes} - A61K 35/14: Blood; Artificial blood (perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42) - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 2039/505: {comprising antibodies} - A61K 2039/892: {Reproductive system [uterus, ovaries, cervix, testes]} - A61P 35/00: Antineoplastic agents - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2319/00: Fusion polypeptide - C07K 2319/02: containing a signal sequence - C07K 2319/03: containing a transmembrane segment - C07K 2319/74: containing a fusion for binding to a cell surface receptor - C12N 2510/00: Genetically modified cells - 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) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present invention includes methods and compositions for treating cancer, whether a solid tumor or a hematologic malignancy. By expressing a chimeric antigen receptor in a monocyte, macrophage or dendritic cell, the modified cell is recruited to the tumor microenvironment where it acts as a potent immune effector by infiltrating the tumor and killing the target cells. One aspect includes a modified cell and pharmaceutical compositions comprising the modified cell for adoptive cell therapy and treating a disease or condition associated with immunosuppression. ## Claims ### Claim 1 A modified cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an anti-HER2 antigen binding domain, an anti-PSMA binding domain, or an anti-mesothelin antigen binding domain, a transmembrane domain, and an intracellular domain of a stimulatory and/or co-stimulatory molecule, wherein the modified cell is a macrophage or a monocyte, and wherein the cell comprises an Ad5F35 adenoviral component. ### Claim 2 (depends on 1) The modified cell of claim 1, wherein the CAR further comprises a hinge domain. ### Claim 3 (depends on 2) The modified cell of claim 2, wherein the hinge domain comprises a CD8 hinge domain or an Ig hinge domain. ### Claim 4 (depends on 1) The modified cell of claim 1, wherein the transmembrane domain comprises a CD8 transmembrane domain, a CD64 transmembrane domain, a CD16 transmembrane domain, a TLR1 transmembrane domain, a TLR2 transmembrane domain, a TLR4 transmembrane domain, a TLR5 transmembrane domain, or a TLR6 transmembrane domain. ### Claim 5 (depends on 1) The modified cell of claim 1, wherein the intracellular domain comprises dual signaling domains. ### Claim 6 (depends on 1) The modified cell of claim 1, wherein the intracellular domain comprises a CD3 zeta intracellular domain, an FcεRI common γ subunit intracellular domain, a Dectin-1 intracellular domain, a CD16 intracellular domain, a TLR1 intracellular domain, a TLR2 intracellular domain, a TLR4 intracellular domain, a TLR5 intracellular domain, or a TLR6 intracellular domain. ### Claim 7 (depends on 1) The modified cell of claim 1, wherein the antigen binding domain is selected from a group consisting of monoclonal antibody, a polyclonal antibody, a synthetic antibody, human antibody, humanized antibody, single domain antibody, single chain variable fragment, and antigen-binding fragments thereof. ### Claim 8 (depends on 1) The modified cell of claim 1, wherein the modified cell expresses one or more M1 markers selected from the group consisting of HLA DR, CD86, CD80, and PDL1. ### Claim 9 (depends on 1) The modified cell of claim 1, wherein the modified cell is a human cell. ### Claim 10 (depends on 1) The modified cell of claim 1, further comprising one or more spacer domains linking the transmembrane domain to the antigen binding domain and/or the intracellular domain. ### Claim 11 (depends on 1) The modified cell of claim 1, further comprising an agent, wherein the agent is 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 or the like, a lipid, a hormone, a microsome, a derivative or a variation thereof, and any combination thereof. ### Claim 12 A modified cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an anti-HER2 antigen binding domain, an anti-PSMA binding domain, or an anti-mesothelin antigen binding domain, a transmembrane domain, and an intracellular domain of a stimulatory and/or co-stimulatory molecule, wherein the modified cell is a macrophage or a monocyte, and wherein the modified cell further comprises one or more adenoviral components. ### Claim 13 (depends on 1) A pharmaceutical composition comprising the modified cell of claim 1 and a pharmaceutically acceptable carrier.