WO2013123061A1 - Bispecific chimeric antigen receptors and therapeutic uses thereof - Google Patents

Bispecific chimeric antigen receptors and therapeutic uses thereof Download PDF

Info

Publication number
WO2013123061A1
WO2013123061A1 PCT/US2013/025953 US2013025953W WO2013123061A1 WO 2013123061 A1 WO2013123061 A1 WO 2013123061A1 US 2013025953 W US2013025953 W US 2013025953W WO 2013123061 A1 WO2013123061 A1 WO 2013123061A1
Authority
WO
WIPO (PCT)
Prior art keywords
receptor
chimeric antigen
cells
bispecific chimeric
antigen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2013/025953
Other languages
English (en)
French (fr)
Inventor
Michael Jensen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Seattle Childrens Hospital
Original Assignee
Seattle Childrens Hospital
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to JP2014556818A priority Critical patent/JP6850528B2/ja
Priority to AU2013221672A priority patent/AU2013221672B2/en
Priority to ES13748596T priority patent/ES2774160T3/es
Priority to US14/376,610 priority patent/US9447194B2/en
Priority to EP13748596.7A priority patent/EP2814846B1/en
Priority to EP19173955.6A priority patent/EP3594245A1/en
Priority to CA2861491A priority patent/CA2861491C/en
Priority to HK15105688.9A priority patent/HK1205144B/en
Application filed by Seattle Childrens Hospital filed Critical Seattle Childrens Hospital
Publication of WO2013123061A1 publication Critical patent/WO2013123061A1/en
Anticipated expiration legal-status Critical
Priority to US15/233,140 priority patent/US10189903B2/en
Priority to AU2017264982A priority patent/AU2017264982B2/en
Priority to US16/240,652 priority patent/US10829556B2/en
Priority to AU2020203137A priority patent/AU2020203137B2/en
Priority to US17/037,381 priority patent/US11639387B2/en
Priority to US18/162,447 priority patent/US12091459B2/en
Priority to AU2023248177A priority patent/AU2023248177A1/en
Priority to US18/806,325 priority patent/US12466885B2/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/179—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/4203—Receptors for growth factors
    • A61K40/4204—Epidermal growth factor receptors [EGFR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/421—Immunoglobulin superfamily
    • A61K40/4211—CD19 or B4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/4221—CD20
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70517—CD8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70521—CD28, CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/27—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by targeting or presenting multiple antigens
    • A61K2239/29—Multispecific CARs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2510/00—Genetically modified cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15021—Viruses as such, e.g. new isolates, mutants or their genomic sequences
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention relates to chimeric antigen receptors and to genetically engineered cells using the same.
  • the invention provides a bispecific chimeric antigen receptor, comprising (a) at least two antigen-specific targeting regions, (b) an extracellular spacer domain, (c) a transmembrane domain, (d) at least one co-stimulatory domain and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control.
  • scFv antigen-specific single chain Fv
  • the invention further provides a combination of a bispecific chimeric antigen receptor and a therapeutic control, wherein the bispecific chimeric antigen receptor comprises (a) at least two antigen-specific targeting regions, (b) an extracellular spacer domain, (c) a transmembrane domain, (d) at least one co-stimulatory domain and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen.
  • scFv single chain Fv
  • the invention further provides a bispecific chimeric antigen receptor, comprising (a) at least two antigen-specific targeting regions, (b) an extracellular spacer domain, (c) a transmembrane domain, (d) at least one co-stimulatory domain and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with truncated epidermal growth factor receptor (EGFRt).
  • EGFRt epidermal growth factor receptor
  • the invention further provides a bispecific chimeric antigen receptor, comprising (a) at least two antigen-specific targeting regions, (b) a CD8ahinge extracellular spacer domain, (c) a CD8a transmembrane domain, (d) a 4-1BB co- stimulatory domain and (vi) a CD3 zeta intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, wherein the bispecific chimeric antigen receptor is co-expressed with EGFRt and wherein the bispecific chimeric antigen receptor and EGFRt are linked via a T2A linker.
  • a bispecific chimeric antigen receptor comprising (a) at least two antigen-specific targeting regions, (b) a CD8ahinge extracellular spacer domain, (c) a CD8a transmembrane domain, (d) a 4-1BB co- stimulatory domain and (vi
  • compositions comprising the above- described bispecific chimeric antigen receptors, a combination of the bispecific chimeric antigen receptors and therapeutic controls, polypeptides encoding the bispecific chimeric antigen receptors, vectors, viruses and genetically engineered cells comprising the bispecific chimeric antigen receptors, vectors, viruses and genetically engineered cells comprising a combination of the bispecific chimeric antigen receptors and therapeutic controls, or combinations thereof, and a pharmaceutically acceptable carrier.
  • Figure 1 depicts a schematic representation of a chimeric antigen receptor of the invention, in accordance with an embodiment of the present invention.
  • ASTR is an antigen-specific targeting region
  • L is a linker
  • ESD is an extracellular spacer domain
  • TM is a transmembrane domain
  • CSD is a co-stimulatory domain
  • ISD is an intracellular signaling domain
  • Figure 2 depicts (a) the components of an anti-CD 19xCD20 CAR, and (b) a complete cDNA packaged into an epHIV-7 lentivirus vector transfer plasmid, in accordance with an embodiment of the present invention.
  • Figure 3 depicts, in accordance with an embodiment of the present invention, the nucleic acid sequence of a bispecific CAR CD19scFv-Gly4Serllinker-CD20scFv-IgG4Hinge- CD28tm-41BB-CD3zeta-T2A-EGFRt_epHIV7.
  • Figure 4 depicts, in accordance with an embodiment of the present invention, the nucleic acid and amino acid sequences of a bispecific CAR CD19scFv-Gly4Serl linker- CD20scFv-IgG4Hinge-CD28tm-41BB-CD3zeta-T2A-EGFRt_epHIV7.
  • Figure 5 depicts, in accordance with an embodiment of the present invention, a CD 19scFv-Gly4Ser 1 linker-CD20scFv-IgG4hinge-CD28tm-CD28gg-CD3Zeta transgene construct.
  • FIG. 6 depicts, in accordance with an embodiment of the present invention, development of a CyCR platform to support exogenous yc independent growth
  • the IL-7Ra constitutive cytokine receptor (CyCR7) consists of the human IL-7 cytokine tethered to the full length human IL-7Ra chain via a (G 4 S) 2 linker.
  • the IL-2RP constitutive cytokine receptor (CyCR2) is identical to CyCR7 except that the IL-7Ra intracellular signaling domain is replaced with the human IL-2/IL-15RP cytoplasmic domain
  • Figure 7 depicts, in accordance with an embodiment of the present invention, the nucleic acid and amino acid sequences of an embodiment of the invention, namely a backbone CAR comprising the hinge region of IgG4, the transmembrane domain of CD28, the costimulatory domain of 4- IBB and the cytoplasmic domain of CD3zeta.
  • Figure 8 depicts, in accordance with an embodiment of the present invention, the nucleic acid sequence of an embodiment of the invention, namely GMCSFRss-CD19scFv- Gly4Serlinker-CD20scFv-huIgGHinge/CH2/CH3-CD28tm/CD28cyto-41BB-CD3zeta.
  • GMCSFRss is the signal sequence from GMCSFR.
  • Figure 9 depicts, in accordance with an embodiment of the present invention, the nucleic acid and amino acid sequences of an embodiment of the invention, namely GMCSFRss- CD 19scFv-Gly4Serlinker-CD20scFv-huIgGHinge/CH2/CH3-CD28tm/CD28cyto-41 BB- CD3zeta.
  • GMCSFRss is the signal sequence from GMCSFR.
  • Figure 10 depicts, in accordance with an embodiment of the present invention, the nucleic acid sequence of an embodiment of the invention, namely the GMCSFRss-CD19scFv- Gly4Serlinker-CD20scFv-CD8aHinge-CD8atm-41BB-CD3zeta-T2A-EGFRt.
  • GMCSFRss is the signal sequence from GMCSFR.
  • Figure 11 depicts, in accordance with an embodiment of the present invention, the nucleic acid and amino acid sequences of an embodiment of the invention, namely GMCSFRss- CD19scFv-Gly4Serlinker-CD20scFv-CD8aHinge-CD8atm-41BB-CD3zeta-T2A- EGFRt.
  • GMCSFRss is the signal sequence from GMCSFR.
  • Figure 12 depicts, in accordance with an embodiment of the present invention, the nucleic acid sequence of an embodiment of an invention namely T2A-EGFRt.
  • Figure 13 depicts, in accordance with an embodiment of the present invention, the nucleic acid and amino acid sequences of an embodiment of the invention, namely T2A-EGFRt.
  • Chimeric antigen receptors are engineered receptors which graft an immune specificity onto a genetically engineered cell.
  • CAR chimeric antigen receptor
  • Antigen-specific targeting region refers to the region of the CAR which targets specific antigens.
  • the CARs of the invention comprise at least two targeting regions which target at least two different antigens.
  • CARs comprise three or more targeting regions which target at least three or more different antigens.
  • the targeting regions on the CAR are extracellular.
  • the antigen-specific targeting regions comprise an antibody or a functional equivalent thereof or a fragment thereof or a derivative thereof and each of the targeting regions target a different antigen.
  • the targeting regions may comprise full length heavy chain, Fab fragments, single chain Fv (scFv) fragments, divalent single chain antibodies or diabodies, each of which are specific to the target antigen.
  • linked cytokines which leads to recognition of cells bearing the cytokine receptor
  • affibodies affibodies, ligand binding domains from naturally occurring receptors, soluble protein/peptide ligand for a receptor (for example on a tumor cell), peptides, and vaccines to prompt an immune response, which may each be used in various embodiments of the invention.
  • ligand binding domains from naturally occurring receptors for example on a tumor cell
  • soluble protein/peptide ligand for a receptor for example on a tumor cell
  • vaccines to prompt an immune response
  • almost any molecule that binds a given antigen with high affinity can be used as an antigen-specific targeting region, as will be appreciated by those of skill in the art.
  • CAR Chimeric antigen receptor
  • CARs engineered receptors, which graft an antigen specificity onto cells (for example T cells such as naive T cells, central memory T cells, effector memory T cells or combination thereof). CARs are also known as artificial T-cell receptors, chimeric T-cell receptors or chimeric immunoreceptors.
  • the CARs of the invention comprise at least two antigen-specific targeting regions, an extracellular domain, a transmembrane domain, one or more co- stimulatory domains, and an intracellular signaling domain.
  • the two or more antigen- specific targeting regions target at least two different antigens and may be arranged in tandem and separated by linker sequences. In an embodiment, the extracellular spacer domain is optional.
  • the CAR is a bispecific CAR. A bispecific CAR is specific to two different antigens.
  • Co-stimulatory domain refers to the portion of the CAR which enhances the proliferation, survival and/or development of memory cells.
  • the CARs of the invention may comprise one or more co-stimulatory domains.
  • Each co-stimulatory domain comprises the costimulatory domain of any one or more of, for example, members of the TNFR superfamily, CD28, CD137 (4-lBB), CD134 (OX40), DaplO, CD27, CD2, CD5, ICAM-1, LFA-1(CD1 la/CD18), Lck, TNFR-I, TNFR-II, Fas, CD30, CD40 or combinations thereof.
  • Extracellular spacer domain refers to the hydrophilic region which is between the antigen-specific targeting region and the transmembrane domain.
  • the CARs of the invention comprise an extracellular spacer domain.
  • the CARs of the invention do not comprise an extracellular spacer domain.
  • the extracellular spacer domains include but are not limited to Fc fragments of antibodies or fragments or derivatives thereof, hinge regions of antibodies or fragments or derivatives thereof, CH2 regions of antibodies, CH3 regions of antibodies, artificial spacer sequences or combinations thereof.
  • extracellular spacer domains include but are not limited to CD8a hinge, and artificial spacers made of polypeptides which may be as small as, for example, Gly3 or CHI and CH3 domains of IgGs (such as human IgG4).
  • the extracellular spacer domain is any one or more of (i) a hinge, CH2 and CH3 regions of IgG4, (ii) a hinge region of IgG4, (iii) a hinge and CH2 of IgG4, (iv) a hinge region of CD8a, (v) a hinge, CH2 and CH3 regions of IgGl , (vi) a hinge region of IgGl or (vi) a hinge and CH2 region of IgGl .
  • Other extracellular spacer domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • Intracellular signaling domain refers to the portion of the CAR which transduces the effector function signal and directs the cell to perform its specialized function.
  • domains that transduce the effector function signal include but are not limited to the ⁇ chain of the T-cell receptor complex or any of its homologs (e.g., ⁇ chain, FcsRly and ⁇ chains, MB 1 (Iga) chain, B29 (Ig ) chain, etc.), human CD3 zeta chain, CD3 polypeptides ( ⁇ , ⁇ and ⁇ ), syk family tyrosine kinases (Syk, ZAP 70, etc.), src family tyrosine kinases (Lck, Fyn, Lyn, etc.) and other molecules involved in T-cell transduction, such as CD2, CD5 and CD28.
  • Other intracellular signaling domains will be apparent to those of skill in the art and may be used in connection with alternate embodiment
  • Linker refers to an oligo- or polypeptide region from about 1 to 100 amino acids in length, which links together any of the domains/regions of the CAR of the invention.
  • Linkers may be composed of flexible residues like glycine and serine so that the adjacent protein domains are free to move relative to one another. Longer linkers may be used when it is desirable to ensure that two adjacent domains do not sterically interfere with one another.
  • Linkers may be cleavable or non-cleavable. Examples of cleavable linkers include 2A linkers (for example T2A), 2A-like linkers or functional equivalents thereof and combinations thereof.
  • the linkers include the picornaviral 2A-like linker, CHYSEL sequences of porcine teschovirus (P2A), Thosea asigna virus (T2A) or combinations, variants and functional equivalents thereof.
  • the linker sequences may comprise Asp-Val/Ile-Glu-X-Asn-Pro-Gly l ' 2A ⁇ Pro l ' 2B ⁇ motif, which results in cleavage between the 2A glycine and the 2B proline.
  • Other linkers will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • Transmembrane domain refers to the region of the CAR which crosses the plasma membrane.
  • the transmembrane domain of the CAR of the invention is the transmembrane region of a transmembrane protein (for example Type I transmembrane proteins), an artificial hydrophobic sequence or a combination thereof.
  • Other transmembrane domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • Antigen loss escape variants refer to cells which exhibit reduced or loss of expression of the target antigen, which antigens are targeted by the CARs of the invention.
  • B-cell associated diseases include B-cell immunodeficiencies, autoimmune diseases and/or excessive/uncontrolled cell proliferation associated with B- cells (including lymphomas and/or leukemias).
  • bispecific CARs of the invention may be used for therapeutic approaches include but are not limited to systemic lupus erythematosus (SLE), diabetes, rheumatoid arthritis (RA), reactive arthritis, multiple sclerosis (MS), pemphigus vulgaris, celiac disease, Crohn's disease, inflammatory bowel disease, ulcerative colitis, autoimmune thyroid disease, X- linked agammaglobulinaemis, pre-B acute lymphoblastic leukemia, systemic lupus erythematosus, common variable immunodeficiency, chronic lymphocytic leukemia, diseases associated with selective IgA deficiency and/or IgG subclass deficiency, B lineage lymphomas (Hodgkin's lymphoma and/or non-Hodgkin's lymphoma), immunodeficiency with thymoma, transient hypogammaglobulinemia and/or hyper IgM syndrome, as well as
  • “Beneficial results” may include, but are in no way limited to, lessening or alleviating the severity of the disease condition, preventing the disease condition from worsening, curing the disease condition, preventing the disease condition from developing, lowering the chances of a patient developing the disease condition and prolonging a patient's life or life expectancy.
  • Cancer and “cancerous” refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth.
  • Examples of cancer include, but are not limited to B-cell lymphomas (Hodgkin's lymphomas and/or non-Hodgkins lymphomas), brain tumor, breast cancer, colon cancer, lung cancer, hepatocellular cancer, gastric cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, cancer of the urinary tract, thyroid cancer, renal cancer, carcinoma, melanoma, head and neck cancer, brain cancer, and prostate cancer, including but not limited to androgen-dependent prostate cancer and androgen-independent prostate cancer.
  • B-cell lymphomas Hodgkin's lymphomas and/or non-Hodgkins lymphomas
  • gastric cancer pancreatic cancer
  • cervical cancer ovarian cancer
  • liver cancer bladder cancer
  • cancer of the urinary tract thyroid cancer
  • renal cancer carcinoma, melanoma
  • head and neck cancer brain cancer
  • prostate cancer including but not limited
  • Co-express refers to simultaneous expression of two or more genes.
  • Genes may be nucleic acids encoding, for example, a single protein or a chimeric protein as a single polypeptide chain.
  • the CARs of the invention may be co- expressed with a therapeutic control (for example truncated epidermal growth factor (EGFRt)), wherein the CAR is encoded by a first polynucleotide chain and the therapeutic control is encoded by a second polynucleotide chain.
  • EGFRt truncated epidermal growth factor
  • the first and second polynucleotide chains are linked by a nucleic acid sequence that encodes a cleavable linker.
  • the polynucleotides encoding the CAR and the therapeutic control system may be linked by IRES sequences. Alternately, the CAR and the therapeutic control are encoded by two different polynucleotides that are not linked via a linker but are instead encoded by, for example, two different vectors. Further, the CARs of the invention may be co-expressed with a therapeutic control and CCR, a therapeutic control and DHFR (for example mutant DHFR) or a therapeutic control and CCR and DHFR (for example mutant DHFR).
  • the CAR, therapeutic control and CCR may be co-expressed and encoded by first, second and third polynucleotide sequences, respectively, wherein the first, second and third polynucleotide sequences are linked via IRES sequences or sequences encoding cleavable linkers. Alternately, these sequences are not linked via linkers but instead are encoded via, for example, separate vectors.
  • the CAR, therapeutic control and DHFR (for example mutant DHFR) may be co-expressed and encoded by first, second and fourth polynucleotide sequences, respectively, wherein the first, second and fourth polynucleotide sequences are linked via IRES sequences or via sequences encoding cleavable linkers.
  • these sequences are not linked via linkers but instead encoded via, for example, separate vectors.
  • the CAR, therapeutic control, CCR and DHFR may be co-expressed and encoded by first, second, third and fourth polynucleotide sequences, respectively, wherein the first, second, third and fourth polynucleotide sequences are linked via IRES sequences or sequences encoding cleavable linkers.
  • these sequences are not linked via linkers but instead are encoded via, for example, separate vectors. If the aforementioned sequences are encoded by separate vectors, these vectors may be simultaneously or sequentially transfected.
  • Conditions include physiological states in which diseased cells may be targeted with the CARs of the invention, expressing, for example, antibodies against specific antigens on the diseased cells.
  • antigens which may be targeted include but are not limited to antigens expressed on B-cells (such as CD 19 and CD20), antigens expressed on carcinomas, sarcomas, lymphomas, leukemia, germ cell tumors, blastomas, antigens expressed on various immune cells, and antigens expressed on cells associated with various hematologic diseases, autoimmune diseases, and/or inflammatory diseases.
  • Disease targeted by genetically modified cells encompasses the targeting of any cell involved in any manner in any disease by the genetically modified cells of the invention, irrespective of whether the genetically modified cells target diseased cells or healthy cells to effectuate a therapeutically beneficial result.
  • the genetically modified cells include but are not limited to genetically modified T-cells, NK cells, hematopoietic stem cells, pluripotent embryonic stem cells or embryonic stem cells.
  • the genetically modified cells express the CARs of the invention, which CARs may target any of the antigens expressed on the surface of target cells.
  • antigens which may be targeted include but are not limited to antigens expressed on B-cells; antigens expressed on carcinomas, sarcomas, lymphomas, leukemia, germ cell tumors, and blastomas; antigens expressed on various immune cells; and antigens expressed on cells associated with various hematologic diseases, autoimmune diseases, and/or inflammatory diseases.
  • antigens expressed on B-cells include but are not limited to antigens expressed on B-cells; antigens expressed on carcinomas, sarcomas, lymphomas, leukemia, germ cell tumors, and blastomas; antigens expressed on various immune cells; and antigens expressed on cells associated with various hematologic diseases, autoimmune diseases, and/or inflammatory diseases.
  • Other antigens that may be targeted will be apparent to those of skill in the art and may be targeted by the CARs of the invention in connection with alternate embodiments thereof.
  • Effector function refers to the specialized function of a differentiated cell. Effector function of a T-cell, for example, may be cytolytic activity or helper activity including the secretion of cytokines.
  • Genetically modified cells refer to cells that express the CAR of the invention.
  • Immunocell refers to the cells of the mammalian immune system including but not limited to antigen presenting cells, B-cells, basophils, cytotoxic T-cells, dendritic cells, eosinophils, granulocytes, helper T-cells, leukocytes, lymphocytes, macrophages, mast cells, memory cells, monocytes, natural killer cells, neutrophils, phagocytes, plasma cells and T-cells.
  • antigen presenting cells B-cells, basophils, cytotoxic T-cells, dendritic cells, eosinophils, granulocytes, helper T-cells, leukocytes, lymphocytes, macrophages, mast cells, memory cells, monocytes, natural killer cells, neutrophils, phagocytes, plasma cells and T-cells.
  • Immuno response refers to immunities including but not limited to innate immunity, humoral immunity, cellular immunity, immunity, inflammatory response, acquired (adaptive) immunity, autoimmunity and/or overactive immunity.
  • “Mammal” as used herein refers to any member of the class Mammalia, including, without limitation, humans and nonhuman primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs, and the like.
  • the term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be included within the scope of this term.
  • Polynucleotide as used herein includes but is not limited to DNA, RNA, cDNA (complementary DNA), m NA (messenger RNA), rRNA (ribosomal RNA), shRNA (small hairpin RNA), snRNA (small nuclear RNA), snoRNA (short nucleolar RNA), miRNA (microRNA), genomic DNA, synthetic DNA, synthetic RNA, and/or tRNA.
  • naked DNA refers to DNA encoding a CAR cloned in a suitable expression vector in proper orientation for expression.
  • Viral vectors which may be used include but are not limited SIN lentiviral vectors, retroviral vectors, foamy virus vectors, adeno-associated virus (AAV) vectors, hybrid vectors and/or plasmid transposons (for example sleeping beauty transposon system) or integrase based vector systems.
  • AAV adeno-associated virus
  • Other vectors that may be used in connection with alternate embodiments of the invention will be apparent to those of skill in the art.
  • Single chain variable fragment “single-chain antibody variable fragments” or “scFv” antibodies as used herein refer to forms of antibodies comprising the variable regions of only the heavy and light chains, connected by a linker peptide.
  • Target cell refers to cells which are involved in a disease and can be targeted by the genetically modified cells of the invention (including but not limited to genetically modified T-cells, NK cells, hematopoietic stem cells, pluripotent stem cells, and embryonic stem cells). Other target cells will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • T-cell and "T-lymphocyte” are interchangeable and used synonymously herein. Examples include but are not limited to naive T cells, central memory T cells, effector memory T cells or combinations thereof.
  • Therapeutic agents refers to agents that are used to, for example, treat, inhibit, prevent, mitigate the effects of, reduce the severity of, reduce the likelihood of developing, slow the progression of and/or cure, a disease.
  • Diseases targeted by the therapeutic agents include but are not limited to carcinomas, sarcomas, lymphomas, leukemia, germ cell tumors, blastomas, antigens expressed on various immune cells, and antigens expressed on cells associated with various hematologic diseases, autoimmune diseases, and/or inflammatory diseases.
  • Therapeutic controls as used herein refers to agents that regulate cell proliferation, facilitate cell selection (for example selecting cells which express the chimeric antigen receptors of the invention), facilitate cell tracking or a combination thereof.
  • regulating cell proliferation comprises up-regulating cell proliferation to promote cell propagation. In another embodiment, regulating cell proliferation comprises down-regulating cell proliferation so as to reduce or inhibit cell propagation. In some embodiments, the agents that serve as therapeutic controls may promote enrichment of cells which express the bispecific chimeric antigen receptors which may result in a therapeutic advantage.
  • Transduction refers to the introduction of a foreign nucleic acid into a cell using a viral vector.
  • Transfection refers to the introduction of a foreign nucleic acid into a cell using recombinant DNA technology.
  • transformation means the introduction of a "foreign” (i.e. extrinsic or extracellular) gene, DNA or RNA sequence to a host cell, so that the host cell will express the introduced gene or sequence to produce a desired substance, such as a protein or enzyme coded by the introduced gene or sequence.
  • the introduced gene or sequence may also be called a "cloned” or “foreign” gene or sequence, may include regulatory or control sequences, such as start, stop, promoter, signal, secretion, or other sequences used by a cell's genetic machinery.
  • the gene or sequence may include nonfunctional sequences or sequences with no known function.
  • a host cell that receives and expresses introduced DNA or RNA has been "transformed” and is a “transformant” or a "clone.”
  • the DNA or RNA introduced to a host cell can come from any source, including cells of the same genus or species as the host cell, or cells of a different genus or species
  • Treatment and “treating,” as used herein refer to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition, prevent the pathologic condition, pursue or obtain beneficial results, or lower the chances of the individual developing the condition even if the treatment is ultimately unsuccessful.
  • Those in need of treatment include those already with the condition as well as those prone to have the condition or those in whom the condition is to be prevented.
  • Tumor refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues.
  • Vector refers to the vehicle by which a polynucleotide sequence (e.g. a foreign gene) can be introduced into a host cell, so as to transform the host and promote expression (e.g. transcription and translation) of the introduced sequence.
  • Vectors include plasmids, phages, viruses, etc.
  • the chimeric antigen receptors may overcome conventional therapeutic failures due to, for example, outgrowth of antigen loss escape variants that can arise in the course of various therapies when a single antigen is targeted.
  • the invention is directed to, among other things, nucleic acid sequences and amino acid sequences encoding CARs, vectors comprising CARs, viruses comprising CARs, genetically modified cells comprising the CARs (redirected cells) and methods of making and using them.
  • the CARs are bispecific CARs.
  • the CARs target and bind three or more different antigens.
  • the present invention relates to CARs (for example bispecific CARs), nucleic acid sequences encoding the CARs (for example bispecific CARs), the vectors comprising the nucleic acids encoding the CARs (for example bispecific CARs), viruses comprising the nucleic acid sequences encoding the CARs (for example bispecific CARs), host cells (such as genetically modified cells) expressing the CARs (for example bispecific CARs), combinations of CARs (for example bispecific CARs) and therapeutic controls and methods of making and using the CARs (for example bispecific CARs) as therapeutic agents.
  • the CARs of the invention target at least two different antigens.
  • the CARs are co-expressed with a therapeutic control; for instance, truncated epidermal growth factor receptor (EGFRt), chimeric cytokine receptors (CCR) and/or dihydroxyfolate receptor (DHFR) (e.g., mutant DHFR).
  • EGFRt epidermal growth factor receptor
  • CCR chimeric cytokine receptors
  • DHFR dihydroxyfolate receptor
  • the polynucleotides encoding the CAR and the therapeutic control(s) may be linked via IRES sequences or via polynucleotide sequences encoding cleavable linkers.
  • the CARs of the invention are constructed so that they may be expressed in cells, which in turn proliferate in response to the presence of at least one molecule that interacts with at least one antigen-specific targeting region, for instance, an antigen.
  • therapeutic controls for use with the CARs of the invention comprise any one or more of truncated epidermal growth factor receptor (EGFRt), thymidine kinase, cytosine deaminase, nitroreductase, xanthine-guanine phosphoribosyl transferase, human caspase 8, human caspase 9, purine nucleoside phosphorylase, linamarase/linamarin/glucose oxidase, deoxyribonucleoside kinase, horseradish peroxidase (HRP)/indole-3-acetic (IAA), Gamma-glutamylcysteine synthetase, CD20/alphaCD20, CD34/thymidine kinase chimera, dox-depedent caspase-2, mutant thymidine kinase (HSV-TKSR39) or AP1903/Fas system.
  • EGFRt
  • the CARs of the invention are linked to EGFRt via a cleavable linker or IRES sequences.
  • a bispecific CAR is linked to EGFRt via a cleavable linker or IRES sequences.
  • the CARs described herein may be synthesized as single polypeptide chains and may comprise at least two antigen-specific targeting regions, an extracellular spacer domain, a transmembrane domain, one or more co-stimulatory domains and an intracellular signaling domain.
  • the antigen-specific targeting regions are at the N- terminus, arranged in tandem and are separated by a linker peptide.
  • the antigen-specific targeting region is linked to an extracellular spacer domain which is linked to the transmembrane domain.
  • the transmembrane domain is linked to the co-stimulatory domain.
  • the co -stimulatory domain is linked to the intracellular signaling domain which is at the C-terminus.
  • the multiple co- stimulatory domains may be arranged in tandem with the transmembrane domain at its N- terminus and the intracellular signaling domain at its C-terminus.
  • Polynucleotides encoding these polypeptides may further comprise an N-terminal signal sequence which directs the CAR to the cell surface as a type I transmembrane protein.
  • the antigen- specific targeting region may be extracellular-facing and the intracellular signaling domain may be cytoplasmic.
  • Figure 1 shows a schematic of a chimeric antigen receptor of the invention.
  • an extracellular spacer domain in the CAR is optional.
  • the antigen-specific targeting regions are at the N-terminus, arranged in tandem, and separated by a linker peptide.
  • the antigen-specific targeting region may be linked to the transmembrane domain.
  • the transmembrane domain may be linked to the co- stimulatory domain.
  • the co-stimulatory domain may be linked to the intracellular signaling domain, which is at the C-terminus. If more than one co-stimulatory domain is used, the multiple co-stimulatory domains may be arranged in tandem with the transmembrane domain at its N-terminus and the intracellular signaling domain at its C- terminus.
  • Polynucleotides encoding these polypeptides may further comprise an N- terminal signal sequence which directs the CAR to the cell surface as a type I transmembrane protein.
  • the antigen-specific targeting region may be extracellular-facing and the intracellular signaling domain may be cytoplasmic.
  • the CARs of the invention may target several (such as two or more, three or more) different antigens.
  • the CAR is a bispecific CAR and targets two different antigens.
  • the antigen-specific targeting regions of the CAR may be arranged in tandem and may be separated by linker peptides.
  • the antigens targeted by the CAR may be antigens on single diseased cell (such as a cancerous B-cell) or antigens that are expressed on separate cells that each contribute to the disease.
  • the antigens targeted by the CAR are antigens which are either directly or indirectly involved in the disease.
  • a bispecific CAR at least two different antigen-specific antibodies or fragments thereof or derivatives thereof may be cloned into the antigen-specific targeting region.
  • the antibodies may be specific for any, but at least two, distinct antigens of choice.
  • the antibody specific to the antigen may be the Fab fragment of the antibody or the single chain variable fragment (scFv) of the antibody.
  • Figure 2 shows an embodiment of the invention depicting a CAR specific to CD 19 and CD20.
  • scFvs specific to multiple, but at least two different antigens may be cloned upstream (i.e., to N-terminus) of the IgG 4 -CD28-zeta domains so long as the target-antigens are expressed on cells that are targetable by the genetically modified cells described below.
  • Such techniques are explained fully in the literature. (Sambrook et al, "Molecular Cloning: A Laboratory Manual” (1989), Current Protocols in Molecular Biology. Volumes I-III [Ausubel, R. M., ed. (1994)], Cell Biology: A Laboratory Handbook.
  • each antigen-specific targeting region comprises the full-length IgG heavy chain (specific for the target antigen) having the VH, CHI, hinge, and the CH2 and CH3 (Fc) Ig domains, if the VH domain alone is sufficient to confer antigen-specificity ("single-domain antibodies").
  • the full length IgG heavy chain may be linked to the co- stimulatory domain and the intracellular signaling domain via the appropriate transmesmbrane domain. If both, the VH and the VL domains, are necessary to generate a fully active antigen-specific targeting region, the VH-containing CAR and the full-length lambda light chain (IgL) are both introduced into the cells to generate an active antigen- specific targeting region.
  • an extracelluar spacer domain may be linked between the antigen- specific binding domain and the transmembrane domain.
  • the cells include but are not limited to T-lymphocytes (T-cells), natural killer cells, hematopoietic stem cells and/or pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny.
  • T-cells T-lymphocytes
  • each antigen-specific targeting region of the CAR comprises at least two single chain antibody variable fragments (scFv), each specific for a different target antigen.
  • scFvs in which the C-terminus of one variable domain (V H or V L ) is tethered to the N-terminus of the other (V L or V H , respectively) via a polypeptide linker, have been developed without significantly disrupting antigen binding or specificity of the binding.
  • the linker connects the N-terminus of the V H with the C-terminus of V L or the C-terminus of V H with the N-terminus of V L .
  • These scFvs lack the constant regions (Fc) present in the heavy and light chains of the native antibody.
  • the scFvs, specific for at least two different antigens, are arranged in tandem and linked to the co-stimulatory domain and the intracellular signaling domain via a transmembrane domain.
  • an extracelluar spacer domain may be linked between the antigen-specific binding region and the transmembrane domain.
  • each scFv fragment may be fused to all or a portion of the constant domains of the heavy chain.
  • the resulting antigen-specific targeting region specific for at least two different antigens, is joined to the co-stimulatory domain and the intracellular signaling domain via a transmembrane domain.
  • an extracelluar spacer domain may be linked between the antigen-specific binding domain and the transmembrane domain.
  • each antigen-specific targeting region of the CAR comprises a divalent (or bivalent) single-chain variable fragment (di-scFvs, bi-scFvs).
  • CARs comprising at least two antigen-specific targeting regions would express two scFvs specific for each of the two antigens.
  • the resulting antigen-specific targeting region specific for at least two different antigens, is joined to the co-stimulatory domain and the intracellular signaling domain via a transmembrane domain.
  • an extracelluar spacer domain may be linked between the antigen-specific binding domain and the transmembrane domain.
  • each antigen-specific targeting region of the CAR comprises a diabody.
  • the scFvs are created with linker peptides that are too short for the two variable regions to fold together, driving the scFvs to dimerize.
  • Still shorter linkers one or two amino acids lead to the formation of trimers, the so-called triabodies or tribodies. Tetrabodies may also be used.
  • two or more individual antigen-specific targeting regions are connected to each other, either covalently or noncovalently, on a single protein molecule.
  • An oligo- or polypeptide linker, an Fc hinge or membrane hinge region may be used to connect these domains to each other.
  • the CARs of the present invention may comprise two or more of the different antigen-specific targeting regions connected together in different combinations.
  • two or more antigen- specific targeting regions containing immunoglobulin sequences e.g. scFvs and/or single-domain antibodies
  • the antigen-specific targeting region of the CAR targets antigens specific for cancer, inflammatory disease, neuronal- disorders, diabetes, cardiovascular disease, infectious diseases or a combination thereof.
  • antigens which may be targeted by the CARs (for example bispecific CARs) of the invention include but are not limited to antigens expressed on B-cells, antigens expressed on carcinomas, sarcomas, lymphomas, leukemia, germ cell tumors, blastomas, antigens expressed on various immune cells, and antigens expressed on cells associated with various hematologic diseases, autoimmune diseases, and/or inflammatory diseases.
  • the CARs of the invention which are specific for at least two different target antigens, may be capable of redirecting the effector function of the expressing-cells to either of both of the target antigens.
  • This feature of the construct may overcome the issue of antigen loss escape variants when targeting, for example, genetically unstable B-cell lineage malignancies using single antigen-specificity.
  • Antigens specific for cancer which may be targeted by the CARs (for example bispecific CARs) of the invention include but are not limited to any one or more of 4- IBB, 5T4, adenocarcinoma antigen, alpha-fetoprotein, BAFF, B-lymphoma cell, C242 antigen, CA- 125, carbonic anhydrase 9 (CA-IX), C-MET, CCR4, CD 152, CD 19, CD20, CD200, CD22, CD221, CD23 (IgE receptor), CD28, CD30 (TNFRSF8), CD33, CD4, CD40, CD44 v6, CD51, CD52, CD56, CD74, CD80, CEA, CNT0888, CTLA-4, DR5, EGFR, EpCAM, CD3, FAP, fibronectin extra domain-B, folate receptor 1, GD2, GD3 ganglioside, glycoprotein 75, GPNMB, HER2/neu, HGF, human scatter factor receptor kinase, IGF-1 receptor
  • CARs which target the above antigens include but are not limited to bispecific CARs, bispecific CARs co-expressed with EGFRt, bispecific CARs co-expressed with EGFRt and CCR, bispecific CARs co- expressed with EGFRt and DHFR (for example mutant DHFR) or bispecific CARs co- expressed with EGFRt and CDR and DHFR (for example mutant DHFR).
  • the bispecific chimeric antigen receptors target and bind at least two different antigens.
  • pairings of at least two antigens bound by the bispecific CARs of the invention include but are not limited to CD 19 and CD20, CD 19 and CD22, CD20 and LI -CAM, LI -CAM and GD2, EGFR and LI -CAM, EGFR and C- MET, EGFR and HER2, C-MET and HER2 and EGFR and ROR1.
  • Other pairings of antigens specific for cancer will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • the bispecific chimeric antigen receptor targets CD 19 and CD20.
  • CARs which target the above antigens include but are not limited to bispecific CARs, bispecific CARs co-expressed with EGFRt, bispecific CARs co-expressed with EGFRt and CCR, bispecific CARs co-expressed with EGFRt and DHFR (for example mutant DHFR) or bispecific CARs co-expressed with EGFRt and CDR and DHFR (for example mutant DHFR).
  • Antigens specific for inflammatory diseases which may be targeted by the CARs of the invention include but are not limited to any one or more of AOC3 (VAP-1), CAM-3001, CCL11 (eotaxin-1), CD125, CD147 (basigin), CD154 (CD40L), CD2, CD20, CD23 (IgE receptor), CD25 (a chain of IL-2 receptor), CD3, CD4, CD5, IFN-a, IFN- ⁇ , IgE, IgE Fc region, IL-1, IL-12, IL-23, IL-13, IL-17, IL-17A, IL-22, IL-4, IL-5, IL-5, IL-6, IL-6 receptor, integrin a4, integrin ⁇ 4 ⁇ 7, Lama glama, LFA-1 (CD1 la), MEDI-528, myostatin, OX-40, rhuMAb ⁇ 7, scleroscin, SOST, TGF beta 1, TNF-a or VEGF-A.
  • antigens specific for inflammatory diseases will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • CARs which target the above antigens include but are not limited to bispecific CARs, bispecific CARs co-expressed with EGFRt, bispecific CARs co-expressed with EGFRt and CCR, bispecific CARs co-expressed with EGFRt and DHFR (for example mutant DHFR) or bispecific CARs co-expressed with EGFRt and CDR and DHFR (for example mutant DHFR).
  • Antigens specific for neuronal disorders which may be targeted by the CARs of the invention include but are not limited to any one or more of beta amyloid or MABT5102A.
  • antigens specific for neuronal disorders will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • CARs which target the above antigens include but are not limited to bispecific CARs, bispecific CARs co-expressed with EGFRt, bispecific CARs co-expressed with EGFRt and CCR, bispecific CARs co-expressed with EGFRt and DHFR (for example mutant DHFR) or bispecific CARs co-expressed with EGFRt and CDR and DHFR (for example mutant DHFR).
  • Antigens specific for diabetes which may be targeted by the CARs of the invention include but are not limited to any one or more of L- ⁇ or CD3.
  • CARs which target the above antigens include but are not limited to bispecific CARs, bispecific CARs co-expressed with EGFRt, bispecific CARs co-expressed with EGFRt and CCR, bispecific CARs co-expressed with EGFRt and DHFR (for example mutant DHFR) or bispecific CARs co-expressed with EGFRt and CDR and DHFR (for example mutant DHFR).
  • Antigens specific for cardiovascular diseases which may be targeted by the CARs of the invention include but are not limited to any one or more of C5, cardiac myosin, CD41 (integrin alpha-lib), fibrin II, beta chain, ITGB2 (CD 18) and sphingosine-1 -phosphate.
  • Other antigens specific for cardiovascular diseases will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • CARs which target the above antigens include but are not limited to bispecific CARs, bispecific CARs co-expressed with EGFRt, bispecific CARs co- expressed with EGFRt and CCR, bispecific CARs co-expressed with EGFRt and DHFR (for example mutant DHFR) or bispecific CARs co-expressed with EGFRt and CDR and DHFR (for example mutant DHFR).
  • Antigens specific for infectious diseases which may be targeted by the CARs of the invention include but are not limited to any one or more of anthrax toxin, CCR5, CD4, clumping factor A, cytomegalovirus, cytomegalovirus glycoprotein B, endotoxin, Escherichia coli, hepatitis B surface antigen, hepatitis B virus, HIV-1 , Hsp90, Influenza A hemagglutinin, lipoteichoic acid, Pseudomonas aeruginosa, rabies virus glycoprotein, respiratory syncytial virus and TNF-a.
  • CARs which target the above antigens include but are not limited to bispecific CARs, bispecific CARs co-expressed with EGFRt, bispecific CARs co-expressed with EGFRt and CCR, bispecific CARs co- expressed with EGFRt and DHFR (for example mutant DHFR) or bispecific CARs co- expressed with EGFRt and CDR and DHFR (for example mutant DHFR).
  • target antigens include but are not limited to surface proteins found on cancer cells in a specific or amplified fashion (e.g. the IL-14 receptor, CD 19, CD20 and CD40 for B-cell lymphoma, the Lewis Y and CEA antigens for a variety of carcinomas, the Tag72 antigen for breast and colorectal cancer, EGF-R for lung cancer, folate binding protein and the HER-2 protein which is often amplified in human breast and ovarian carcinomas), or viral proteins (e.g.
  • gpl20 and gp41 envelope proteins of HIV envelope proteins from the Hepatitis B and C viruses, the glycoprotein B and other envelope glycoproteins of human cytomegalovirus, the envelope proteins from oncoviruses such as Kaposi's sarcoma-associated Herpes virus).
  • Other potential targets of the CARs of the invention include CD4, where the ligand is the HIV gpl20 envelope glycoprotein, and other viral receptors, for example ICAM, which is the receptor for the human rhinovirus, and the related receptor molecule for poliovirus.
  • Additional targets of the CARs of the invention include antigens involved in B-cell associated diseases.
  • Yet further targets of the CARs of the invention will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention. Co-stimulatory domains of chimeric antigen receptors
  • the CARs of the invention may also comprise a co-stimulatory domain. This domain may enhance cell proliferation, cell survival and development of memory cells.
  • the CARs of the invention may comprise one or more co-stimulatory domains.
  • Each co- stimulatory domain comprises the co-stimulatory domain of any one or more of, for example, members of the TNFR super family, CD28, CD137 (4-1BB), CD134 (OX40), DaplO, CD27, CD2, CD5, ICAM-1, LFA-1, Lck, TNFR-1, TNFR-II, Fas, CD30, CD40 or combinations thereof.
  • Co-stimulatory domains from other proteins may also be used with the CARs of the invention.
  • co-stimulatory domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention. If a CAR comprises more than one co-stimulatory domain, these domains may be arranged in tandem, optionally separated by a linker.
  • Extracellular spacer domain of chimeric antigen receptor Extracellular spacer domain of chimeric antigen receptor
  • the CARs of the invention may further comprise an extracellular spacer domain.
  • this domain facilitates proper protein folding.
  • the extracellular spacer domain comprises a hydrophilic region which is attached to the antigen-specific targeting region and the transmembrane domain.
  • Extracellular spacer domains may include, but are not limited to, Fc fragments of antibodies or fragments or derivatives thereof, hinge regions of antibodies or fragments or derivatives thereof, CH2 regions of antibodies, CH3 regions antibodies, artificial spacer sequences or combinations thereof.
  • Examples of extracellular spacer domains include but are not limited to CD 8a hinge, artificial spacers made of polypeptides such as Gly3, or CHI, CH3 domains of IgG's (such as human IgG4).
  • the extracellular spacer domain may be (i) a hinge, CH2 and CH3 regions of IgG4, (ii) a hinge region of IgG4, (iii) a hinge and CH2 of IgG4, (iv) a hinge region of CD8a, (v) a hinge, CH2 and CH3 regions of IgGl, (vi) a hinge region of IgGl or (vi) a hinge and CH2 of IgGl or a combination thereof. Additional extracellular spacer domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • the CARs of the invention may also comprise a transmembrane domain.
  • the transmembrane domain may comprise the transmembrane sequence from any protein which has a transmembrane domain, including any of the type I, type II or type III transmembrane proteins.
  • the transmembrane domain of the CAR of the invention may also comprise an artificial hydrophobic sequence.
  • the transmembrane domains of the CARs of the invention may be selected so as not to dimerize. Additional transmembrane domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • the CARs of the invention may also comprise an intracellular signaling domain.
  • This domain may be cytoplasmic and may transduce the effector function signal and direct the cell to perform its specialized function.
  • intracellular signaling domains include, but are not limited to, ⁇ chain of the T-cell receptor or any of its homologs ⁇ e.g., ⁇ chain, FcsRly and ⁇ chains, MB1 (Iga) chain, B29 (Ig ) chain, etc.), CD3 polypeptides ( ⁇ , ⁇ and ⁇ ), syk family tyrosine kinases (Syk, ZAP 70, etc.), src family tyrosine kinases (Lck, Fyn, Lyn, etc.) and other molecules involved in T-cell transduction, such as CD2, CD5 and CD28.
  • the intracellular signaling domain may be human CD3 zeta chain, FcyRIII, FcsRI, cytoplasmic tails of Fc receptors, immunoreceptor tyrosine-based activation motif (ITAM) bearing cytoplasmic receptors or combinations thereof. Additional intracellular signaling domains will be apparent to those of skill in the art and may be used in connection with alternate embodiments of the invention.
  • ITAM immunoreceptor tyrosine-based activation motif
  • two or more components of the CARs of the invention are separated by one or more linkers.
  • the first targeting region on the CAR may be separated from the second targeting region on the CAR via a linker.
  • the CAR may be linked to therapeutic controls via a linker.
  • Linkers are oligo- or polypeptides region from about 1 to 100 amino acids in length, that link together any of the domains/regions of the CAR of the invention.
  • the linkers may be for example, 5-12 amino acids in length, 5-15 amino acids in length or 5 to 20 amino acids in length.
  • Linkers may be composed of flexible residues like glycine and serine so that the adjacent protein domains are free to move relative to one another. Longer linkers, for example those longer than 100 amino acids, may be used in connection with alternate embodiments of the invention, and may be selected to, for example, ensure that two adjacent domains do not sterically interfere with one another. Examples of linkers which may be used in the instant invention include but are not limited to 2A linkers (for example T2A), 2A-like linkers or functional equivalents thereof.
  • Therapeutic controls regulate cell proliferation, facilitate cell selection (for example selecting cells which express the chimeric antigen receptors of the invention) or a combination thereof.
  • regulating cell proliferation comprises up- regulating cell proliferation to promote cell propagation.
  • regulating cell proliferation comprises down-regulating cell proliferation so as to reduce or inhibit cell propagation.
  • the agents that serve as therapeutic controls may promote enrichment of cells which express the bispecific chimeric antigen receptors which may result in a therapeutic advantage.
  • agents which serve as therapeutic controls may biochemically interact with additional compositions so as to regulate the functioning of the therapeutic controls.
  • EGFRt (a therapeutic control) may biochemically interact with cetuximab so as to regulate the function of EGFRt in selection, tracking, cell ablation or a combination thereof.
  • therapeutic controls include but are not limited to any one or more of truncated epidermal growth factor receptor (EGFRt), thymidine kinase, cytosine deaminase, nitroreductase, xanthine-guanine phosphoribosyl transferase, human caspase 8, human caspase 9, purine nucleoside phosphorylase, linamarase/linamarin/glucose oxidase, deoxyribonucleoside kinase, horseradish peroxidase (HRP)/indole-3-acetic (IAA), Gamma-glutamylcysteine synthetase, CD20/alphaCD20, CD34/thymidine kinase chimera, dox-depedent caspase-2, mutant thymidine kinase (HSV-TKSR39), AP1903/Fas system, a chimeric cytokine receptor (EG
  • agents which regulate the functioning of the therapeutic controls include but are not limited to any one or more of Herceptin, methotrexate, cetuximab, thymidine analogs (for example ganciclovir), (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 5- flurocytosine (5-FC), 5-(azaridin-l-yl)-2, 4-dinitrobenzamide (CB1954), 6-thioguanine, a synthetic dimerizing drug (for example API 903), fludarabine phosphate, linamarin (lin), nucleoside analogs (for exmaple BVDU, difluorodeoxycytidine (dFdC), ⁇ - ⁇ -D- arabinofuranosylthymine (ara-T)), indole-3 -acetic (IAA), l-buthionine-S,R-sulfoximine (BSO), rituximab (RTX), doxycycline,
  • the CARs of the invention may be synthesized as single polypeptide chains.
  • the polynucleotide sequence encoding the CAR may be, for example, in the following configuration in the N-terminal to C-terminal direction: N-terminal signal sequence - antigen-specific targeting region 1 - linker - antigen-specific targeting region 2 - extracellular spacer domain - transmembrane domain - co-stimulatory domain - intracellular signaling domain.
  • such a CAR may comprise two or more co-stimulatory domains.
  • the polynucleotide sequence encoding the CAR may be in the following configuration in the N-terminal to C-terminal direction: N-terminal signal sequence - antigen-specific targeting region 1 - linker - antigen-specific targeting region 2 - transmembrane domain - co-stimulatory domain - intracellular signaling domain.
  • such a CAR may comprise two or more co-stimulatory domains.
  • the polynucleotide sequence encoding the CAR may be in the following configuration in the N-terminal to C-terminal direction: N-terminal signal sequence - antigen-specific targeting region 1 - linker - antigen-specific targeting region 2 - linker - (antigen-specific targeting region) n - transmembrane domain - co-stimulatory domain - intracellular signaling domain.
  • Such a CAR may further comprise an extracellular spacer domain.
  • Each antigen-specific targeting region may be separated by a linker.
  • such a CAR may comprise two or more co-stimulatory domains.
  • an exemplary backbone for a may CAR comprise, in the N-terminus to C-terminus orientation, IgG4hinge-CD28tm-41BB-CD3zeta, wherein the extracellular spacer domain is the IgG4 hinge region, the transmembrane domain is the transmembrane region from CD28, the co- stimulatory domain is from 4- IBB and the intracellular signaling domain is from the CD3 zeta chain ( Figure 7). At least two or more antigen- specific targeting regions may be inserted N-terminal to the IgG4 hinge.
  • the invention provides nucleic acid sequences of an exemplary embodiment of the invention where the CAR is specific to CD 19 and CD20.
  • the sequence encoding a bispecific anti-CD 19xCD20 CAR is set forth in Figure 3, 8 or 10.
  • the sequence encoding a bispecific anti-CD 19xCD20 CAR is set forth in Figure 4, 9 or 11.
  • the bispecific CAR comprises scFvs specific for CD 19 and CD20 with each scFv separated by a linker, joined to an extracellular spacer domain, which is joined to the co-stimulatory and intracellular signaling domains via a transmembrane domain.
  • the exemplary CAR depicts a set of scFv sequences
  • any scFv specific for CD 19 and CD20 may be used.
  • the bispecific CAR specific for CD 19 and CD20 is CD19scFv- Gly4Serlinker-CD20scFv-IgG4-Hinge-CD28tm-41BB(cyto)-zeta(cyto) and is encoded by the sequences set forth in Figures 3 and 4.
  • This bispecific CAR comprises single chain Fv fragments specific for CD 19 and CD20 linked by a Gly4Ser linker, an IgG4 hinge extracellular spacer domain, a CD28 transmembrane domain, a 4 IBB costimulatory domain and the cytoplasmic domain from CD3 zeta chain.
  • the bispecific CAR specific for CD 19 and CD20 comprises CD19scFv-Gly4serlinker-CD20scFv-hulgG4-hingeCH2CH3-CD28tm/cyto-41BB-zeta ( Figures 9-10).
  • This bispecific CAR comprises single chain Fv fragments specific for CD 19 and CD20 linked by a Gly4Ser linker, a human IgG4 hinge, CH2 and CH3 extracellular spacer domain, a CD28 transmembrane domain, a 4- IBB costimulatory domain and the cytoplasmic domain from CD3 zeta chain.
  • the bispecific CAR specific for CD 19 and CD20 is CD 19- Gly4serlinker-CD20scFv-CD8ahinge-CD8aTM-41BBcostim-zetacyto ( Figures 11-12).
  • This bispecific CAR comprises single chain Fv fragments specific for CD 19 and CD20 linked by a Gly4Ser linker, a CD8alpha hinge extracellular spacer domain, a CD8alpha transmembrane domain, a 4 IBB costimulatory domain and the cytoplasmic domain from CD3 zeta chain.
  • Human epidermal growth factor receptor (huEGFR)(EGFR; ErbB-1, FIERI in humans) is a receptor tyrosine kinase of the ErbB family of growth factor receptors that is not expressed by cells of the hematopoietic and lymphopoietic systems.
  • Ligand (EGF, TGF- a) binding occurs within N-terminal extracellular domains I and II of EGFR resulting from transition of receptor tyrosine kinase inactive monomers to active homodimers.
  • Extracellular domain III of EGFR contains the binding sites of antibodies (for example cetuximab (Erbitux), an IgGl chimeric antibody).
  • human EGFR may be rendered incapable of binding ligands (EGF, TGF-a) by removal of domains I and II, and devoid of signaling activity by deletion of its cytoplasmic tail, while retaining an intact antibody binding site (for example cetuximab binding site), for example in extracellular domain III, IV or a combination thereof (Wang et al., A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells Blood 118(5)1255-1263).
  • a truncated EGFRt polypeptide described herein has at least three uses for genetic engineering of cell-based therapies: ex vivo cell purification, in vivo cell tracking, and cell ablation.
  • EGFRt for use as a therapeutic control with the CARs of the invention, binds any one or more of EGFR-specific siRNA, a small molecule that targets EGFR, an anti-EGFR-antibody or a combination thereof.
  • EGFRt comprises the sequence set forth in Figures 12 or 13 or sequences that are about 70%, about 75%, about 80%, about 85%, about 90% or about 95% homologous to the sequences set forth in Figures 12 or 13.
  • huEGFRt may be co-expressed with the CARs of the invention so as to purify cells expressing the CARs (for example ex vivo cell purification), track cells (for example in vitro or in vivo cell tracking) expressing the CARs or regulate cells (for example in vivo or in vitro or ex vivo) expressing the CARs by triggering cell ablation as required.
  • the CARs are bispecific CARs.
  • CCR Chimeric cytokine receptor
  • the invention provides T cells with an intrinsic yc cytokine signaling mechanism.
  • the utility of forced constitutive chimeric cytokine receptors IL-2/IL-15RP (CyCR2) and IL-7Ra (CyCR7) receptor signals were compared.
  • the chimeric cytokine receptors have the ability to improve the survival, persistence, and in vivo engraftment of cytotoxic T cells (CTLs).
  • CTLs cytotoxic T cells
  • the CARs of the invention may be co- expressed with CCR.
  • a bispecific CAR may be co-expressed with EGFRt and CCR.
  • a bispecific CAR may be co-expressed with CCR.
  • chimeric cytokine receptor include but are not limited to IL-7 cytokine-linker- IL7Ra, IL- 7 cytokine-linker-extracellular domain of IL-7Ra-transmembrane domain of IL-7Ra- cytoplasmic domain of IL-2RP, IL-7 cytokine-linker-IL2Rp.
  • a CCR comprising IL-7 cytokine-linker- IL7Ra comprises an N-terminal signal sequence joined to the N-terminus of the IL-7 cytokine which is linked via a linker to extracellular, transmembrane and cytoplasmic domains of IL-7Ra (the alpha chain of the IL-7 receptor).
  • a CCR comprising IL-7 cytokine-linker-extracellular domain of IL-7Ra -transmembrane domain of IL-7Ra-cytoplasmic domain of IL-2RP comprises an N-terminal signal sequence joined to the N-terminus of the IL-7 cytokine which is linked via a linker to the extracellular domain and transmembrane domain of IL-7Ra and to the cytoplasmic domain of IL-2R (the beta chain of the IL-2 receptor).
  • a CCR comprising IL-7 cytokine-linker-IL2R comprises N-terminal signal sequence joined to the N-terminus of the IL-7 cytokine which is linked via a linker to extracellular, transmembrane and cytoplasmic domains of IL-2R .
  • DHFR Dihydroxy folate Receptor
  • CD19CAR CD19-specific chimeric antigen receptor
  • the CARs of the invention may be co- expressed with DHFR (for example mutant DHFR).
  • the bispecific CAR may be co-expressed with EGFRt, CCR and DHFR (including mutant DHFR). Alternately, the bispecific CAR may be co-expressed with EGFRt and DHFR (including mutant DHFR).
  • selection markers that may be used with the CARs of the invention include but are not limited to methylated-DNA-protein-cysteine methyltransferase (MDMT), inosine monophosphate dehydrogenase II (IMDHP2) or a combination thereof. MDMT makes cells resistant to chemotherapy and therefore may be used if synergy between chemotherapy and T cell therapy is desired.
  • MDMT methylated-DNA-protein-cysteine methyltransferase
  • IMDHP2 inosine monophosphate dehydrogenase II
  • Vectors encoding the CARs of the invention are also provided herein.
  • Vectors encoding CARs also encode EGFRt.
  • vectors encoding CARs and EGFRt also encode CCR or DHFR (for example mutant DHFR).
  • vectors encoding CARs and EGFRt also encode CCD and DHFR (for example mutant DHFR).
  • the vectors may encode a bispecific CAR and EGFRt, a bispecific CAR and EGFRt and CCR, a bispecific CAR and EGFRt and DHFR (for example mutant DHFR) or a bispecific CAR and EGFRt and CCR and DHFR (for example mutant DHFR).
  • Vectors which may be used to express the CARs of the invention include but are not limited to lentivirus vectors, gamma retrovirus vectors, foamy virus vectors, AAV vectors, adeno virus vectors, engineered hybrid viruses, naked DNA (including but not limited to transposon mediated vectors, such as Sleeping Beauty, Piggybak, and Integrases such as Phi31.
  • the bisepcific CAR specific to CD 19 and CD20 disclosed herein is expressed via a lentiviral vector as illustrated in Figure 5.
  • the invention also provides genetically engineered cells which comprise and stably express the CAR of the invention.
  • the CAR expressed by the genetically engineered cell may comprise at least two antigen-specific targeting regions, an extracellular domain, a transmembrane domain, one or more co -stimulatory domains and an intracellular signaling domain.
  • the polynucleotide sequence encoding the CAR may also comprise an N-terminal signal sequence.
  • the CAR is a bispecific CAR.
  • Each of the at least two antigen-specific targeting regions, extracellular spacer domain, transmembrane domain, one or more co -stimulatory domains and an intracellular signaling domain are described above.
  • the antigen-specific targeting domains may be capable of specifically binding, in an MHC unrestricted manner, an antigen which is not normally bound by a T-cell receptor in that manner.
  • the genetically engineered cells that express the CARs (for example bispecific CARs) of the invention co-express EGFRt.
  • the genetically engineered cells that express the CARs (for example bispecific CARs) co- express EGFRt and CCR.
  • the genetically engineered cells that express the CARs (for example bispecific CARs) co-express EGFRt and DHFR (for example mutant DHFR).
  • the genetically engineered cells that express the CARs (for example bispecific CARs) co-express EGFRt, CCR and DHFR (for example mutant DHFR).
  • the genetically engineered cells express a CAR having at least two antigen-specific targeting regions which are specific for at least two different target antigens.
  • the antigen-specific targeting regions comprise target-specific antibodies or functional equivalents or fragments or derivatives thereof.
  • the antigen-specific antibody may be the Fab fragment of the antibody or the single chain variable fragment (scFv) of the antibody.
  • Genetically engineered cells which may comprise and express the CARs of the invention include, but are not limited to, T-lymphocytes (T-cells), na ' ive T cells (T N ), memory T cells (for example, central memory T cells (TC M ), effector memory cells (T EM )), natural killer cells, hematopoietic stem cells and/or pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny.
  • the genetically engineered cells are autologous cells.
  • individual T-cells of the invention may be CD4+/CD8-, CD4-/CD8+, CD4-/CD8- or CD4+/CD8+.
  • the T- cells may be a mixed population of CD4+/CD8- and CD4-/CD8+ cells or a population of a single clone.
  • CD4+ T-cells of the invention may produce IL-2, IFNy, TNFa and other T-cell effector cytokines when co-cultured in vitro with cells expressing the target antigens (for example CD20+ and/or CD 19+ tumor cells).
  • CD8 + T-cells of the invention may lyse antigen-specific target cells when co-cultured in vitro with the target cells.
  • T cells may be any one or more of CD45RA + CD62L + naive cells, CD45RO CD62I7 central memory cells, CD62L " effector memory cells or a combination thereof (Berger et al., Adoptive transfer of virus-specific and tumor-specific T cell immunity. Curr Opin Immunol 2009 21(2)224-232).
  • Genetically modified cells may be produced by stably transfecting cells with DNA encoding the CAR of the invention.
  • DNA encoding the CAR of the invention may also encode EGFRt, CCR and/or DHFR (for example mutant DHFR).
  • a first polynucleotide encodes the CAR (for example bispecific CAR) and is linked via IRES sequences or a polynucleotide that encodes a cleavable linker, to a second polynucleotide that encodes EGFRt.
  • the first polynucleotide encodes the CAR (for example bispecific CAR) and is linked via IRES sequences or a polynucleotide that encodes a cleavable linker, to a second polynucleotide that encodes EGFRt and the first or second polynucleotides are linked to a third polynucleotide that encodes CCR or DHFR (for example mutant DHFR), also via IRES sequences or a polynucleotide that encodes a cleavable linker.
  • CAR for example bispecific CAR
  • a third polynucleotide that encodes CCR or DHFR for example mutant DHFR
  • the first polynucleotide encodes the CAR (for example bispecific CAR) and is linked via IRES sequences or a polynucleotide that encodes a cleavable linker, to a second polynucleotide that encodes EGFRt and the first and second polynucleotides are linked to a third polynucleotide that encodes CCR and a fourth polynucleotide that encodes DHFR (for example mutant DHFR) via IRES sequences or a polynucleotide that encodes a cleavable linker.
  • Viral vectors are commonly used to carry heterologous genes into cells ⁇ e.g., T-cells).
  • viral vectors which may be used to generate genetically modified cells include but are not limited to SIN lentiviral vectors, retroviral vectors, foamy virus vectors, adeno-associated virus (AAV) vectors and/or plasmid transposons ⁇ e.g., sleeping beauty transposon system).
  • SIN lentiviral vectors retroviral vectors
  • foamy virus vectors foamy virus vectors
  • AAV adeno-associated virus
  • plasmid transposons ⁇ e.g., sleeping beauty transposon system.
  • a method of stably transfecting and re-directing cells is by electroporation using naked DNA.
  • naked DNA By using naked DNA, the time required to produce redirected cells may be significantly reduced.
  • Additional methods to genetically engineer cells using naked DNA encoding the CAR of the invention include but are not limited to chemical transformation methods (e.g., using calcium phosphate, dendrimers, liposomes and/or cationic polymers), non-chemical transformation methods (e.g., electroporation, optical transformation, gene electrotransfer and/or hydrodynamic delivery) and/or particle-based methods (e.g., impalefection, using a gene gun and/or magnetofection).
  • the transfected cells demonstrating presence of a single integrated un-rearranged vector and expression of the CAR may be expanded ex vivo.
  • the cells selected for ex vivo expansion are CD8 + and demonstrates the capacity to specifically recognize and lyse antigen-specific target cells.
  • Viral transduction methods may also be used to generate redirected cells which express the CAR of the invention.
  • Cell types that may be used to generate genetically modified cells expressing the bispecific CAR of the invention include but are not limited to T- lymphocytes (T-cells), natural killer cells, hematopoietic stem cells and/or pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny.
  • the cells comprising the CAR of the invention will expand in number in response to the binding of one or more antigens to the antigen-specific targeting regions of the CAR.
  • the invention also provides a method of making and expanding cells expressing a CAR. The method comprises transfecting or transducing the cells with the vector expressing the CAR and stimulating the cells with cells expressing the target antigens, recombinant target antigens, or an antibody to the receptor to cause the cells to proliferate, so as to make and expand T-cells.
  • the cells may be any one or more of T-lymphocytes (T-cells), natural killer (NK) cells, hematopoietic stem cells (HSCs) or pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny.
  • T-cells T-lymphocytes
  • NK natural killer
  • HSCs hematopoietic stem cells
  • pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny.
  • the genetically engineered cells of the invention express a bispecific CAR which is specific for CD 19 and CD20 antigens.
  • a genetically engineered T-cell expresses the bispecific CARs CD19scFv-Gly4ser-linker- CD20scFv-hulgG4-hinge-CD28-41BB(cyto)-zeta(cyto) or CD19scFv-Gly4ser-linker- CD20scFv-hulgG4-hingeCH2CH3-CD28tm/cyto-zeta or CD 19-Gly4serlinker- CD20scFv-CD8alphahinge-CD8alphaTM-41BBcostim-zetacyto.
  • the invention provides a method of making and expanding T-cells expressing a CD19-specific and CD20-specific CAR.
  • the method comprises using a lentivirus to transduce CD3xCD28 bead-stimulated purified central memory T- cells (such as T-cells from peripheral blood) with the vector expressing the CD 19 and CD20 bispecific CAR, growing the T-cells in the presence of rhuIL-2 and/or IL-15 and restimulating the T-cells with CD19 + and CD20 + cells, recombinant CD 19 and CD20, or an antibody to the receptor to cause the T-cells to proliferate, so as to make and expand CD19-specific and CD20-specific T-cells.
  • the CARs of the invention may be used to overcome therapeutic failures arising from antigen loss escape variants, to reduce resistance to existing therapies and/or to treat diseases associated with the antigens targeted by the CARs.
  • the invention also provides methods for treating a disease associated with the antigen targeted by the CAR of the invention in a subject in need thereof.
  • the method comprises providing a composition comprising the CAR of the invention and administering an effective amount of the composition so as to treat the disease associated with the antigen in the subject.
  • the invention also provides methods for overcoming therapeutic failures arising from antigen loss escape variants in disease states ⁇ e.g., B-cell diseases) in subjects in need thereof.
  • the method comprises providing a composition comprising the CAR of the invention and administering an effective amount of the composition so as to treat the disease associated with the antigen in the subject.
  • the composition comprises a polynucleotide encoding the CAR, a protein comprising the CAR or genetically modified cells comprising the CAR.
  • the genetically modified cells of the composition are T-lymphocytes (T-cells), na ' ive T cells (T N ), memory T cells (for example, central memory T cells (TC M ), effector memory cells (T EM )), natural killer (NK) cells, hematopoietic stem cells (HSCs) or pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny, which express the CAR of the invention.
  • T-cells T-lymphocytes
  • T N memory T cells
  • TC M central memory T cells
  • T EM effector memory cells
  • NK natural killer cells
  • HSCs hematopoietic stem cells
  • pluripotent embryonic/induced stem cells capable of giving rise to therapeutically relevant progeny, which express the CAR of the invention.
  • the present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a therapeutically effective amount of the CAR (for example, bispecific CAR) of the invention.
  • the CAR of the invention in the composition may be any one or more of a polynucleotide encoding the CAR, a protein comprising the CAR or genetically modified cells comprising the CAR.
  • the composition may further comprise polynucleotides encoding EGFRt, CCR and/or DHFR (for example mutant DHFR), proteins co-expressed with the CAR including EGFRt, CCR and/or DHFR or genetically modified cells that express the CAR and co- express EGFRt, CCR and/or DHFR.
  • “Pharmaceutically acceptable excipient” means an excipient that is useful in preparing a pharmaceutical composition that is generally safe, non-toxic, and desirable, and includes excipients that are acceptable for veterinary use as well as for human pharmaceutical use. Such excipients may be solid, liquid, semisolid, or, in the case of an aerosol composition, gaseous.
  • compositions according to the invention may be formulated for delivery via any route of administration.
  • Route of administration may refer to any administration pathway known in the art, including but not limited to aerosol, nasal, oral, intravenous, intramuscular, intraperitoneal, inhalation, transmucosal, transdermal, parenteral, implantable pump, continuous infusion, topical application, capsules and/or injections.
  • compositions according to the invention can also contain any pharmaceutically acceptable carrier.
  • “Pharmaceutically acceptable carrier” as used herein refers to a pharmaceutically acceptable material, composition, or vehicle that is involved in carrying or transporting a compound of interest from one tissue, organ, or portion of the body to another tissue, organ, or portion of the body.
  • the carrier may be a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, or a combination thereof.
  • Each component of the carrier must be “pharmaceutically acceptable” in that it must be compatible with the other ingredients of the formulation. It must also be suitable for use in contact with any tissues or organs with which it may come in contact, meaning that it must not carry a risk of toxicity, irritation, allergic response, immunogenicity, or any other complication that excessively outweighs its therapeutic benefits.
  • compositions according to the invention can also be encapsulated, tableted or prepared in an emulsion or syrup for oral administration.
  • Pharmaceutically acceptable solid or liquid carriers may be added to enhance or stabilize the composition, or to facilitate preparation of the composition.
  • Liquid carriers include syrup, peanut oil, olive oil, glycerin, saline, alcohols and water.
  • Solid carriers include starch, lactose, calcium sulfate, dihydrate, terra alba, magnesium stearate or stearic acid, talc, pectin, acacia, agar or gelatin.
  • the carrier may also include a sustained release material such as glyceryl monostearate or glyceryl distearate, alone or with a wax.
  • the pharmaceutical preparations are made following the conventional techniques of pharmacy involving milling, mixing, granulation, and compressing, when necessary, for tablet forms; or milling, mixing and filling for hard gelatin capsule forms.
  • a liquid carrier When a liquid carrier is used, the preparation will be in the form of syrup, elixir, emulsion or an aqueous or non-aqueous suspension.
  • Such a liquid formulation may be administered directly p.o. or filled into a soft gelatin capsule.
  • the pharmaceutical compositions according to the invention may be delivered in a therapeutically effective amount.
  • the precise therapeutically effective amount is that amount of the composition that will yield the most effective results in terms of efficacy of treatment in a given subject. This amount will vary depending upon a variety of factors, including but not limited to the characteristics of the therapeutic compound (including activity, pharmacokinetics, pharmacodynamics, and bioavailability), the physiological condition of the subject (including age, sex, disease type and stage, general physical condition, responsiveness to a given dosage, and type of medication), the nature of the pharmaceutically acceptable carrier or carriers in the formulation, and the route of administration.
  • Example 1 is provided to better illustrate the claimed invention and are not to be interpreted as limiting the scope of the invention. To the extent that specific materials are mentioned, it is merely for purposes of illustration and is not intended to limit the invention. One skilled in the art may develop equivalent means or reactants without the exercise of inventive capacity and without departing from the scope of the invention.
  • Example 1 is provided to better illustrate the claimed invention and are not to be interpreted as limiting the scope of the invention. To the extent that specific materials are mentioned, it is merely for purposes of illustration and is not intended to limit the invention. One skilled in the art may develop equivalent means or reactants without the exercise of inventive capacity and without departing from the scope of the invention.
  • Example 1 is provided to better illustrate the claimed invention and are not to be interpreted as limiting the scope of the invention. To the extent that specific materials are mentioned, it is merely for purposes of illustration and is not intended to limit the invention. One skilled in the art may develop equivalent means or reactants without the exercise of inventive capacity and without departing from the scope of the invention.
  • Example 1 is provided to
  • Figure 1 is a schematic representation of the bispecific chimeric antigen receptor of the invention.
  • Figure 2 depicts the components of bispecific anti-CD 19xanti-CD20 bispecific CAR.
  • Figure 2 also depicts a schematic of the complete cDNA packaged into epHIV-7 lentivirus vector transfer plasmid.
  • Figures 3 and 4 show the nucleic and amino acid sequences of an exemplary bispecific CAR, namely GMCSFss-CD19scFv-Gly4Serllinker-CD20scFv-IgG4Hinge- CD28tm-41BBzeta-T2A-EGFRt_epHIV7.
  • Example 2 Example 2
  • Figure 5 is a schematic showing the vector construct of an exemplary CAR of the invention, namely, the CD19scFv-CD20scFv-IgG4-CD28tm-CD28costim-CD3zeta transgene construct.
  • the CD19scFv-CD20scFv-IgG4-CD28tmCD28costim-CD3zeta transgene was assembled using the one-step isothermal DNA assembly method previously described by Gibson et. al. (Enzymatic assembly of DNA molecules upto several hindred kilobases. Nature Methods. 2009;6:343-345).
  • V L and V H domains of the CD 19 scFv construct was sequenced from a CD19CAR-CD28-Zeta transgene previously described. Schmitz N, Dreger P, Glass B, Sureda A. Allogeneic transplantation in lymphoma: current status. Haematologica. 2007;92(11): 1533-1548) through polymerase chain reaction (PCR).
  • V H and V L domains of the CD20 scFv were assembled by spliced-overlap polymerase chain reaction using a CD20R-CD28-Zeta transgene previously described (Michael Jensen et al., CD20 is a molecular target for scFvFc:zeta receptor redirected T-cells: implications for cellular immunotherapy of CD20 + malignancy. Biology of Blood and Marrow Transplant. 1998;4:75-83).
  • the V H and the V L domains of CD 19 scFv and CD20 scFv were linked with an 18-residue linker peptide as previously described.
  • the IgG4-CD28tm-CD28costim domain was sequenced using the CD19R-CD28-CD3zeta transgene by PCR.
  • the CD3zeta-T2A-EGFRt_epHIV7 lentiviral destination vector was prepared by Nhel and RsrII restriction digestion of the CD19R-CD28 portion from a CD19R-CD28-Zeta-T2A-EGFRt_ epHIV7 plasmid previously described (Seitaro Terakura et al., Generation of CD19-CAR modified CD8+ T-cells derived from virus-specific central memory T-cells. Blood. Oct. 26, 2011).
  • the final CD19scFv-CD20scFv-IgG4-CD28tm-CD28costim-CD3zeta construct was assembled by the one-step isothermal Gibson DNA assembly method using the restriction digested Zeta-epHIV7 destination vector and the CD19scFv, CD20scFv, and IgG4- CD28tm-CD28costim- DNA fragments with primers for each containing a 30 bp overlap at the 5' terminus.
  • flap Contains polypurine track sequence and central
  • CMV promoter CMV promoter to generate viral genome RNA
  • Example 3 HEK 293T-cells were transfected with anti-CD 19xCD20CAR-T2A-EGFRt epHIV-7 transfer plasmid or with anti-CD20xCD 19CAR-T2A-EGFRt epHIV-7 transfer plasmid. Transfected cells were stained with biotinylated anti-Fc antibodies and streptavidin PE (SA-PE) and then were subjected to flow cytometric analysis for detection of expression of the above two CARs. Both the anti-CD 19xCD20 CAR and the anti-CD20xCD19 CAR were expressed on transfected HEK 293T cells.
  • SA-PE biotinylated anti-Fc antibodies and streptavidin PE
  • epHIV7 lentivirus vector also encoded EGFRt together with monospecific anti-CD 19 CAR, monospecific anti-CD20 CAR or bispecific anti-CD 19xCD20.
  • epHIV7 lentivirus vector also encoded EGFRt together with monospecific anti-CD 19 CAR, monospecific anti-CD20 CAR or bispecific anti-CD 19xCD20.
  • Transfected cells were stained with biotinlylated anti-EGFR antibodies and SA-PE and then were subjected to flow cytometric analysis for detection of EGFRt expression and co-expression of monospecific or bispecific CARs.
  • monospecific anti-CD 19 CAR 51% expressed EGFRt
  • monospecific anti-CD20 CAR 38.5% expressed EGFRt
  • bispecific anti-CD 19xCD20 CAR 63.8% expressed EGFRt.
  • T cell receptor (TCR) complex in transfected cells was also detected in the same transfected cells using FITC-conjugated anti-TCRa and anti-TCRp antibodies staining and flow cytometric analysis.
  • Example 5 H9 cells were genetically modified to express CD 19, or CD20, or both CD 19 and CD20.
  • Cells were stained with anti-CD 19 and anti-CD20 antibodies and then were subject to flow cytometric analysis to detect the expression of CD 19 and CD20.
  • Cytometric analysis confirmed the desired expression profile of CD19 + CD20 " , CD19 " CD20 + , and CD19 + CD20 + H9 cells, namely, genetically engineered H9 cells expressed CD 19, or CD20, or both CD 19 and CD20 thereby simulating cancer target cells, which contain antigen-negative antigen loss escape variants.
  • these cell lines were subsequently used as target cells to stimulate CAR-expressing T-cell lines, which act as effector cells to kill target cells.
  • SUP-B15 and DHL-6 cell lines were analyzed using anti-CD 19 APC and anti-CD20 PE staining and flow cytometric analysis.
  • SUP-B15 cell line expressed high level of CD 19 with low level of CD20 (thus CD19 + CD20 " ), and DHL- 16 cell line expressed high level of CD20 with low level of CD 19 (thus CD19 ⁇ CD20 + ).
  • Effector cells are primary human T-cells lentivirally transduced to express monospecific anti-CD 19 CAR, monospecific anti-CD20 CAR or bispecific anti- CD 19xCD20 CAR.
  • the bispecific anti-CD 19xCD20 CAR effector T-cells effectively lysed all CD19 + CD20 " , CD19 " CD20 + , and CD19 + CD20 + target cells, which include CD19 + CD20 " H9 cells, CD19 " CD20 + H9 cells, CD19 + CD20 + H9 cells and SUP-B15 cells.
  • monospecific CAR expressing T-cell lines fail to lyse antigen-negative antigen loss escape variants, which escaped from the monospecific CAR effector cells.
  • the anti-CD 19 CAR effector T-cells failed to lyse CD19 " CD20 + targets and the anti- CD20 CAR effector T-cells failed to lyse CD19 + CD20 " targets.
  • Example 7 Bispecific CAR-expressing CD4 enriched T-cells were activated for cytokine secretion (Interferon gamma (IFN-g, IFN- ⁇ )) upon stimulation by CD19 + CD20 " , CD19 " CD20 + , and CD19 + CD20 + target cells, which include CD19 + CD20 " H9 cells, CD19 " CD20 + H9 cells, CD19 CD20 + H9 cells and SUP-B15 cells.
  • IFN- ⁇ content was measured by cytokine bead array of culture supernatants of T-cells and target cells after 24-hours of co-culture.
  • bispecific CAR-expressing CD4 enriched T-cells secreted at least 2500 pg/ml INF-g upon stimulation by every type of target cells.
  • monospecific CAR expressing T-cell lines were not activated for cytokine INF-g secretion upon stimulation by antigen-negative antigen loss escape variants, which escaped from the monospecific CAR effector cells.
  • CD 19 CAR T-cells failed to secrete IGN- ⁇ upon co-culture with CD19 ⁇ CD20 + target cells and CD20 CAR T-cells failed to secrete IGN- ⁇ upon co-culture with CD19 + CD20 " target cells.
  • CD4 enriched CD19R CD8 enriched CD19R
  • CD4 enriched CD20R CD8 enriched CD20R
  • EGFRt truncated epidermal growth factor receptor
  • T2A sequence truncated epidermal growth factor receptor
  • EGFRt may be linked to and co-expressed with other chimeric antigen receptors, for example, bispecific chimeric antigen receptors .
  • huEGFRt truncated EGFR
  • domain I and II of EGFRt have been deleted while domains III and IV have been retained.
  • the CD19CAR-T2A-EGFRt-epHIV7 lentiviral construct contains: (1) the chimeric antigen receptor (CAR) sequence consisting of the V H and V L gene segments of the CD19-specific FMC63 monoclonal antibody (mAb), an IgG4 hinge-Cm-Cm, the transmembrane, and cytoplasmic signaling domains of the co-stimulatory molecule CD28, and the cytoplasmic domain of the CD3 ⁇ chain (Kowolik CK. et al., CD28 costimuation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res.
  • CAR chimeric antigen receptor sequence consisting of the V H and V L gene segments of the CD19-specific FMC63 monoclonal antibody (mAb), an IgG4 hinge-Cm-Cm, the transmembrane, and cytoplasmic signaling domains of the co-
  • biotinylated cetuximab was used for either immunomagnetic selection or FACS sorting of huEGFRt + cells. Applicants used biotinylated cetuximab in conjunction with commercially available antibiotin microbeads for the immunomagnetic selection of human T cells transduced with a self-inactivating lentivirus that directs the co-expression of CD 19CAR and huEGFRt.
  • PBMCs or purified central memory (CD45RO CD62L + TC M ) or effector memory (CD45RO + CD62L + T EM ) T-cell subsets were stimulated with anti-CD3/anti-CD28 beads and then transduced by lentiviral vector to generate a panel of primary human T-cell lines, of which 2.6%-40% expressed huEGFRt and CAR.
  • the unselected cells were labeled with biotinylated cetuximab and anti-biotin microbeads; and then were separated to consistently obtain a selected cell population, of which 90% express huEGFRt and CAR.
  • Unselected T cells and selected fraction were stained with biotinylated-cetuximab and either PE-conjugated streptavidin or PE-conjugated anti-biotin Ab, and then were subject to flow cytometric analysis.
  • Selection of CD19CAR + EGFRt + cells was performed either 3 days after transduction of OKT3 blasts (enriched from 38% to 98%), or after 1 rapid expansion cycle of transduced effector memory CD62LCD45RO -derived cells (enriched from 20% to 96%>), after 3 rapid expansion cycles of transduced CMVpp65 -specific TCM-derived cells (enriched from 12% to 91%), or after 2 rapid expansion cycles of transduced CD8 + TCM-derived cells (enriched from 3% to 97%).
  • CD19CAR-T2A-EGFRt-IMPDH2dm constructs contained in lentiviral vectors include codon optimized sequence portions of the CD19-specific, CD28 co-stimulatory CAR (CD19CAR), followed by the self-cleavable T2A, and selection markers huEGFRt and IMPDH2dm (a double mutant of the inosine monophosphate dehydrogenase 2 gene that allows for cell survival upon addition of mycophenolate 27), along with the Elongation Factor 1 promoter sequences (EF-lp), the GM-CSF receptor alpha chain signal sequences (GMCSFRss), and the 3 nucleotide stop codon.
  • EF-lp Elongation Factor 1 promoter sequences
  • GMCSFRss GM-CSF receptor alpha chain signal sequences
  • huEGFRt can serve as a cell surface marker unique to transduced human T cells and enable subsequent cetuximab-based immunomagnetic purification of stable huEGFRt-expressing cell populations which also express CARs.
  • Applicants performed immunohistochemical analysis of paraffin- embedded femurs from engrafted mice and detected huEGFRt + cells in the bone marrow. These data support the utility of huEGFRt to serve as a tracking marker for quantifying the frequency and tissue distribution of adoptively transferred T cells.
  • Cetuximab binding to huEGFRt sensitizes human T cells to ADCC
  • a valuable feature of a cell surface selection/tracking marker would be its capacity to serve as a target for in vivo cell ablation.
  • Applicants evaluated the extent to which Cetuximab bound to huEGFRt on T cells activates ADCC of huEGFRt + T cells in vitro, and whether Cetuximab administration could attenuate the engraftment of adoptively transferred huEGFRt T cells in NOO/scid mice.
  • Applicants next derived huEGFRt + CTLL-2 murine T cells that were additionally modified to secrete autocrine IL-2 and express the firefly luciferase biophotonic reporter, and adoptively transferred these ffLuc huEGFRt + CTLL-2 cells via intravenous injection to NOD/scz ' ⁇ i mice, which subsequently received Cetuximab or Rituxan.
  • the in vivo engraftment of transferred CTLL-2 was significantly inhibited (97%, P ⁇ .05) in mice that received Erbitux (1 mg intraperitoneally daily).
  • the Cetuximab-mediated elimination of the ffLuc huEGFRt + CTLL-2 cells occurred between 4 and 6 days.
  • This example describes T cells with an intrinsic yc cytokine signaling mechanism, and shows that chimeric cytokine receptors (CCR) IL-2/IL-15RP (CyCR2) and IL-7Ra (CyCR7) have the ability to improve the survival, persistence, and in vivo engraftment of cytotoxic T cells (CTLs).
  • CTLs cytotoxic T cells
  • Truncated CD 19 antigen (CD19t) was linked to CyCR via a T2A linker to show the expression of CyCR on the cell surface.
  • the chimeric cytokine receptors described herein may be linked to the chimeric antigen receptors of the invention, such as bispecific CARs described herein.
  • CyCR chimeric yc cytokine receptors
  • CyCR that provides an IL-2/IL-15RP signal was engineered by tethering the IL-7 cytokine to the extracellular and transmembrane domain of IL-7Ra fused to the cytoplasmic domain of IL-2/IL-15RP (CyCR2). These single chain chimeric receptors are expected to require endogenous yc chain for signaling.
  • CyCR and CD19t are expressed as a single transcript and cleaved post-translationally at the C- terminus of the T2A self-cleaving peptide to yield two separate type 1 membrane proteins CyCR(T2A) and CD19t. Based on expression of two proteins from a single transcript, the ratio of CyCR(T2A) to CD19t expression is 1 : 1, therefore, cell surface CD19t is an indication of CyCR cell surface expression. Lentiviral transduction and expression of these constructs could then be measured by surface CD19t expression, such as that seen in both Jurkat and NK-92 cell lines.
  • CyCR7t truncated IL-7Ra
  • CyCR7t truncated IL-7Ra
  • CyCR7t dimerization with the endogenous yc chain is necessary for signal transduction.
  • the lack of amino acids 1-126 of the extracellular domain of IL-7Ra renders the CyCR7t nonfunctional. Truncated CyCR7 expression does not functionally signal or support cytokine independent cell growth.
  • CyCR2 and CyCR7 could support the growth of CD8 + human primary T cells in the absence of exogenous cytokine
  • Human primary T cells expressing CyCR7t were unable to expand in the absence of exogenous cytokine .
  • Both CyCR2 and CyCR7 were able to support the survival and proliferation of the CD8 + T cells through maintenance of viability, in a manner similar to that of parental cells cultured in 5U/ml and 0.5 U/ml IL-2, respectively.
  • CyCR2 + versus CyCR7 + CTL correlates with increased expression (i.e., MFI of 26 for CyCR7 versus 52 for CyCR2) of Ki67, a nuclear antigen protein present in Gl, S, G2, and M phase of the cell cycle.
  • MFI MFI of 26 for CyCR7 versus 52 for CyCR2
  • Bcl-2 an key antiapoptotic protein induced in response to IL-2 and IL-7 signaling
  • expression was observed for CyCR7 + versus CyCR2 + CTL, supporting the ability of CyCR7 to maintain the survival of the human primary T cells.
  • CyCR2 provides a proliferative advantage while CyCR7 maintains survival for effector CD8 + CTLs.
  • CyCR expressing CD8 T cells exhibit cytokine independent engraftment in vivo
  • CyCR2 + CTLs had impressive significant ( O.007) exogenous cytokine independent engraftment compared to CyCR7 + CTLs and the parental cells.
  • both CyCR7 + CTLs ⁇ 0.03) and CyCR2 + CTLs ( O.0005) had significant exogenous cytokine independent engraftment compared to the parental cells.
  • CyCR2 + CTLs had higher engraftment compared to CyCR7 + CTLs. This indicates that both CyCR7 + CTLs and CyCR2 + CTLs are capable of supporting exogenous cytokine independent engraftment but the total percentage of cells was different.
  • the blood supported higher percent engraftment of CyCR2 + CTLs compared to bone marrow.
  • the bone marrow supported the engraftment of CyCR7 + CTLs over a longer period of time. Importantly, the engraftment was not infinite as the cells were no longer present in the blood and bone marrow at day 48 in either group.
  • Cell intrinsic c cytokine signals can replace the need for exogenous cytokine administration for the support of adoptively transferred CTLs.
  • Providing cell intrinsic cytokine receptors can overcome the major limitation of adoptive immunotherapy; the long-term persistence of adoptively transferred CTL. This may eliminate the need for administration of exogenous cytokine, which may reduce toxicities and bystander effects on endogenous cell types.
  • CD 19 chimeric antigen receptor linked to EGFRt and DHFR can be regulated by methotrexate.
  • the dihydroxyfolate receptor described herein may be linked to the bispecific chimeric antigen receptors of the invention.
  • MTX exerts its antiproliferative effect through competitive inhibition of DHFR, a key enzyme essential for de novo synthesis of thymidylate nucleotides.
  • Applicants designed a lentiviral vector co-expressing hDHFR in conjunction with a CD19-specific chimeric antigen receptor (CD19CAR) and a truncated human EGFR polypeptide as a tracking marker (huEGFRt) each separated by a ribosomal skip T2A sequence.
  • CD19CAR CD19-specific chimeric antigen receptor
  • huEGFRt truncated human EGFR polypeptide as a tracking marker
  • CTLL2 T cells were first transduced with this CD 19C AR-huEGFRt-hDHFR FS lentiviral vector and evaluated for their resistance to MTX. Ten days after lenti-transduction, 7-8 % of the cells were positive for CD19CAR and huEGFRt expression.
  • transduced CTLL2 cells that had been cultured in 0.1 ⁇ MTX for 8 days were re-plated at a wider range of MTX concentrations (up to 0.75 ⁇ ). These transduced and pre-MTX selected cells were able to expand 90-100 fold at MTX concentrations up to 0.25 ⁇ , which is equivalent to non-transduced control CTLL2 expansion in the absence of MTX.
  • transduced primary human T cells with the same CD19CAR-huEGFRt- hDHFR FS lentiviral vector.
  • Purified CD62L + CD45RO + T cells were used as a starting population based on their potential for persistence after adoptive transfer.
  • Ten days after transduction these T cells were cultured in varying concentrations of MTX and assessed for cell number and viability over time. After 10 days, transduced and non-transduced T cells expanded equally (80-fold) in the absence of MTX.
  • transduced T cells maintained a viability of 63%, while non-transduced primary human T cells exhibited strong inhibition of both viability and fold-expansion starting at concentrations as low as 0.025 ⁇ MTX.
  • MTX-mediated enrichment of transgene- expressing cells e.g., 0.025 ⁇ MTX enriched about 54% CD19CAR + and 79% EGFRt + ; 0.05 ⁇ MTX enriched about 76% CD19CAR + and 89% EGFRt + )

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Toxicology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Virology (AREA)
  • Developmental Biology & Embryology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/US2013/025953 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and therapeutic uses thereof Ceased WO2013123061A1 (en)

Priority Applications (16)

Application Number Priority Date Filing Date Title
JP2014556818A JP6850528B2 (ja) 2012-02-13 2013-02-13 二重特異性キメラ抗原受容体およびその治療的使用
AU2013221672A AU2013221672B2 (en) 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and therapeutic uses thereof
ES13748596T ES2774160T3 (es) 2012-02-13 2013-02-13 Receptores de antígenos quiméricos biespecíficos y usos terapéuticos de los mismos
US14/376,610 US9447194B2 (en) 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and encoding polynucleotides thereof
EP13748596.7A EP2814846B1 (en) 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and therapeutic uses thereof
EP19173955.6A EP3594245A1 (en) 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and therapeutic uses thereof
CA2861491A CA2861491C (en) 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and therapeutic uses thereof
HK15105688.9A HK1205144B (en) 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and therapeutic uses thereof
US15/233,140 US10189903B2 (en) 2012-02-13 2016-08-10 Bispecific chimeric antigen receptors and methods of use thereof to treat cancer
AU2017264982A AU2017264982B2 (en) 2012-02-13 2017-11-20 Bispecific chimeric antigen receptors and therapeutic uses thereof
US16/240,652 US10829556B2 (en) 2012-02-13 2019-01-04 Polynucleotides encoding bispecific chimeric antigen receptors
AU2020203137A AU2020203137B2 (en) 2012-02-13 2020-05-13 Bispecific chimeric antigen receptors and therapeutic uses thereof
US17/037,381 US11639387B2 (en) 2012-02-13 2020-09-29 Bispecific chimeric antigen receptors, encoding polynucleotides thereof and methods of use thereof to treat disease
US18/162,447 US12091459B2 (en) 2012-02-13 2023-01-31 Bispecific chimeric antigen receptors, encoding polynucleotides and use of receptors thereof to treat cancer
AU2023248177A AU2023248177A1 (en) 2012-02-13 2023-10-13 Bispecific chimeric antigen receptors and therapeutic uses thereof
US18/806,325 US12466885B2 (en) 2012-02-13 2024-08-15 Bispecific chimeric antigen receptors and encoding polynucleotides, vectors and cells thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261598216P 2012-02-13 2012-02-13
US61/598,216 2012-02-13

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US14/376,610 A-371-Of-International US9447194B2 (en) 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and encoding polynucleotides thereof
US15/233,140 Continuation US10189903B2 (en) 2012-02-13 2016-08-10 Bispecific chimeric antigen receptors and methods of use thereof to treat cancer

Publications (1)

Publication Number Publication Date
WO2013123061A1 true WO2013123061A1 (en) 2013-08-22

Family

ID=48984661

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2013/025953 Ceased WO2013123061A1 (en) 2012-02-13 2013-02-13 Bispecific chimeric antigen receptors and therapeutic uses thereof

Country Status (7)

Country Link
US (6) US9447194B2 (https=)
EP (2) EP3594245A1 (https=)
JP (4) JP6850528B2 (https=)
AU (4) AU2013221672B2 (https=)
CA (1) CA2861491C (https=)
ES (1) ES2774160T3 (https=)
WO (1) WO2013123061A1 (https=)

Cited By (417)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130280220A1 (en) * 2012-04-20 2013-10-24 Nabil Ahmed Chimeric antigen receptor for bispecific activation and targeting of t lymphocytes
US20140274801A1 (en) * 2013-03-14 2014-09-18 Elwha Llc Compositions, methods, and computer systems related to making and administering modified t cells
WO2015057852A1 (en) * 2013-10-15 2015-04-23 The California Institute For Biomedical Research Chimeric antigen receptor t cell switches and uses thereof
WO2015066551A3 (en) * 2013-10-31 2015-06-25 Fred Hutchinson Cancer Research Center Modified hematopoietic stem/progenitor and non-t effector cells, and uses thereof
WO2015095895A1 (en) * 2013-12-20 2015-06-25 Fred Hutchinson Cancer Research Center Tagged chimeric effector molecules and receptors thereof
WO2015105522A1 (en) * 2014-01-13 2015-07-16 Forman Stephen J Chimeric antigen receptors (cars) having mutations in the fc spacer region and methods for their use
WO2015092024A3 (en) * 2013-12-20 2015-08-13 Cellectis Method of engineering multi-input signal sensitive t cell for immunotherapy
WO2015142675A2 (en) 2014-03-15 2015-09-24 Novartis Ag Treatment of cancer using chimeric antigen receptor
CN104974261A (zh) * 2014-04-01 2015-10-14 上海中信国健药业股份有限公司 重组抗her2/ps双特异性抗体、其制备方法和应用
WO2015157391A1 (en) * 2014-04-10 2015-10-15 Seattle Children's Hospital (dba Seattle Children's Research Institute) Method and compositions for cellular immunotherapy
WO2015179801A1 (en) * 2014-05-23 2015-11-26 University Of Florida Research Foundation, Inc. Car based immunotherapy
WO2016014530A1 (en) 2014-07-21 2016-01-28 Novartis Ag Combinations of low, immune enhancing. doses of mtor inhibitors and cars
WO2016016343A1 (en) * 2014-07-31 2016-02-04 Cellectis Ror1 specific multi-chain chimeric antigen receptor
WO2016033570A1 (en) 2014-08-28 2016-03-03 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for cd19
CN105384825A (zh) * 2015-08-11 2016-03-09 南京传奇生物科技有限公司 一种基于单域抗体的双特异性嵌合抗原受体及其应用
WO2016034666A1 (en) * 2014-09-04 2016-03-10 Cellectis Trophoblast glycoprotein (5t4, tpbg) specific chimeric antigen receptors for cancer immunotherapy
WO2016044605A1 (en) 2014-09-17 2016-03-24 Beatty, Gregory Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy
WO2016025454A3 (en) * 2014-08-12 2016-04-07 Anthrogenesis Corporation Car-t lymphocytes engineered to home to lymph node b cell zone, skin, or gastrointestinal tract
WO2016056228A1 (ja) * 2014-10-09 2016-04-14 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
EP2817318A4 (en) * 2012-02-22 2016-04-27 Univ Pennsylvania COMPOSITIONS AND METHOD FOR GENERATING A PERSISTENT POPULATION OF T CELLS FOR CANCER TREATMENT
WO2016064929A1 (en) 2014-10-20 2016-04-28 Juno Therapeutics, Inc. Methods and compositions for dosing in adoptive cell therapy
WO2016070061A1 (en) * 2014-10-31 2016-05-06 The Trustees Of The University Of Pennsylvania Methods and compositions for modified t cells
WO2016073602A2 (en) 2014-11-05 2016-05-12 Juno Therapeutics, Inc. Methods for transduction and cell processing
WO2016090034A2 (en) 2014-12-03 2016-06-09 Novartis Ag Methods for b cell preconditioning in car therapy
WO2016090369A1 (en) * 2014-12-05 2016-06-09 City Of Hope Cs1 targeted chimeric antigen receptor-modified t cells
WO2016090190A1 (en) 2014-12-03 2016-06-09 Juno Therapeutics, Inc. Methods and compositions for adoptive cell therapy
WO2016100232A1 (en) * 2014-12-15 2016-06-23 The Regents Of The University Of California Bispecific or-gate chimeric antigen receptor responsive to cd19 and cd20
WO2016102965A1 (en) * 2014-12-24 2016-06-30 Ucl Business Plc Cell
WO2016109668A1 (en) * 2014-12-31 2016-07-07 Anthrogenesis Corporation Methods of treating hematological disorders, solid tumors, or infectious diseases using natural killer cells
US9394368B2 (en) 2013-02-20 2016-07-19 Novartis Ag Treatment of cancer using humanized anti-EGFRvIII chimeric antigen receptor
WO2016115177A1 (en) 2015-01-12 2016-07-21 Juno Therapeutics, Inc. Modified hepatitis post-transcriptional regulatory elements
WO2016115559A1 (en) 2015-01-16 2016-07-21 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for ror1
WO2016126608A1 (en) 2015-02-02 2016-08-11 Novartis Ag Car-expressing cells against multiple tumor antigens and uses thereof
WO2016141357A1 (en) * 2015-03-05 2016-09-09 Fred Hutchinson Cancer Research Center Immunomodulatory fusion proteins and uses thereof
US9447194B2 (en) 2012-02-13 2016-09-20 Seattle Children's Hospital Bispecific chimeric antigen receptors and encoding polynucleotides thereof
CN105985444A (zh) * 2015-02-05 2016-10-05 博生吉医药科技(苏州)有限公司 一种嵌合抗原受体、以及快速构建嵌合抗原受体的方法及应用
WO2016166568A1 (en) 2015-04-16 2016-10-20 Juno Therapeutics Gmbh Methods, kits and apparatus for expanding a population of cells
US20160311910A1 (en) * 2013-12-06 2016-10-27 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services Thymic stromal lymphopoietin receptor-specific chimeric antigen receptors and methods using same
WO2016172583A1 (en) 2015-04-23 2016-10-27 Novartis Ag Treatment of cancer using chimeric antigen receptor and protein kinase a blocker
WO2016172606A1 (en) 2015-04-23 2016-10-27 Baylor College Of Medicine Cd5 chimeric antigen receptor for adoptive t cell therapy
WO2016174405A1 (en) * 2015-04-27 2016-11-03 Ucl Business Plc Nucleic acid construct for expressing more than one chimeric antigen receptor
WO2016164731A3 (en) * 2015-04-08 2016-11-10 Novartis Ag Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car) - expressing cell
US9499855B2 (en) 2013-03-14 2016-11-22 Elwha Llc Compositions, methods, and computer systems related to making and administering modified T cells
WO2016185035A1 (en) * 2015-05-20 2016-11-24 Cellectis Anti-gd3 specific chimeric antigen receptors for cancer immunotherapy
WO2016196388A1 (en) 2015-05-29 2016-12-08 Juno Therapeutics, Inc. Composition and methods for regulating inhibitory interactions in genetically engineered cells
WO2016210447A1 (en) * 2015-06-26 2016-12-29 University Of Southern California Masking chimeric antigen receptor t cells for tumor-specific activation
EP3027755A4 (en) * 2013-08-02 2017-01-18 The Regents of The University of California Engineering antiviral t cell immunity through stem cells and chimeric antigen receptors
KR20170013941A (ko) * 2014-06-02 2017-02-07 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 Cd-19를 표적화하는 키메라 항원 수용체
WO2017027392A1 (en) 2015-08-07 2017-02-16 Novartis Ag Treatment of cancer using chimeric cd3 receptor proteins
CN106459990A (zh) * 2014-02-07 2017-02-22 麦克马斯特大学 三功能t细胞抗原偶联物及其制备方法和用途
WO2017029512A1 (en) * 2015-08-20 2017-02-23 Autolus Ltd Chimeric cytokine receptor
US9587237B2 (en) 2013-03-14 2017-03-07 Elwha Llc Compositions, methods, and computer systems related to making and administering modified T cells
US20170067022A1 (en) * 2014-02-21 2017-03-09 Cellectis Method for in situ inhibition of regulatory t cells
WO2017053902A1 (en) 2015-09-25 2017-03-30 Abvitro Llc High throughput process for t cell receptor target identification of natively-paired t cell receptor sequences
WO2017053906A1 (en) 2015-09-24 2017-03-30 Abvitro Llc Hiv antibody compositions and methods of use
WO2017060300A1 (en) * 2015-10-07 2017-04-13 Biontech Cell & Gene Therapies Gmbh Antigen receptors and uses thereof
US9624276B2 (en) 2013-10-15 2017-04-18 The California Institute For Biomedical Research Peptidic chimeric antigen receptor T cell switches and uses thereof
KR20170042325A (ko) * 2014-08-28 2017-04-18 바이오아트라, 엘엘씨 변형된 t 세포에 대한 조건부 활성 키메라 항원 수용체
WO2017068419A2 (en) 2015-10-22 2017-04-27 Juno Therapeutics Gmbh Methods, kits, agents and apparatuses for transduction
WO2017068421A1 (en) 2015-10-22 2017-04-27 Juno Therapeutics Gmbh Methods for culturing cells and kits and apparatus for same
WO2017068425A1 (en) 2015-10-22 2017-04-27 Juno Therapeutics Gmbh Methods for culturing cells and kits and apparatus for same
WO2017075433A1 (en) 2015-10-30 2017-05-04 The Regents Of The University Of California Transforming growth factor-beta-responsive polypeptides and their methods for use
WO2017079705A1 (en) 2015-11-05 2017-05-11 Juno Therapeutics, Inc. Chimeric receptors containing traf-inducing domains and related compositions and methods
WO2017079703A1 (en) 2015-11-05 2017-05-11 Juno Therapeutics, Inc. Vectors and genetically engineered immune cells expressing metabolic pathway modulators and uses in adoptive cell therapy
US9657105B2 (en) 2013-03-15 2017-05-23 City Of Hope CD123-specific chimeric antigen receptor redirected T cells and methods of their use
US20170152316A1 (en) * 2015-11-19 2017-06-01 Revitope Limited Functional antibody fragment complementation for a two-components system for redirected killing of unwanted cells
WO2017091786A1 (en) 2015-11-23 2017-06-01 Novartis Ag Optimized lentiviral transfer vectors and uses thereof
WO2017096327A2 (en) 2015-12-03 2017-06-08 Juno Therapeutics, Inc. Compositions and methods for reducing immune responses against cell therapies
WO2017096329A1 (en) 2015-12-03 2017-06-08 Juno Therapeutics, Inc. Modified chimeric receptors and related compositions and methods
JP2017515460A (ja) * 2014-04-03 2017-06-15 セレクティスＣｅｌｌｅｃｔｉｓ 癌免疫療法のためのｃｄ３３特異的キメラ抗原受容体
JP2017515504A (ja) * 2014-05-14 2017-06-15 カースゲン セラピューティクス リミテッドＣａｒｓｇｅｎ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ キメラ抗原受容体タンパク質をコードする核酸およびキメラ抗原受容体タンパク質を発現するｔリンパ球
WO2017114497A1 (en) 2015-12-30 2017-07-06 Novartis Ag Immune effector cell therapies with enhanced efficacy
US20170246278A1 (en) * 2014-10-17 2017-08-31 Baylor College Of Medicine Bipartite and tripartite signaling immune cells
WO2017149515A1 (en) 2016-03-04 2017-09-08 Novartis Ag Cells expressing multiple chimeric antigen receptor (car) molecules and uses therefore
WO2017161208A1 (en) 2016-03-16 2017-09-21 Juno Therapeutics, Inc. Methods for determining dosing of a therapeutic agent and related treatments
WO2017161212A1 (en) 2016-03-16 2017-09-21 Juno Therapeutics, Inc. Methods for adaptive design of a treatment regimen and related treatments
WO2017165683A1 (en) 2016-03-23 2017-09-28 Novartis Ag Cell secreted minibodies and uses thereof
WO2017165571A1 (en) 2016-03-22 2017-09-28 Seattle Children's Hospital (dba Seattle Children's Research Institute) Early intervention methods to prevent or ameliorate toxicity
US9777061B2 (en) 2014-07-21 2017-10-03 Novartis Ag Treatment of cancer using a CD33 chimeric antigen receptor
WO2017181119A2 (en) 2016-04-15 2017-10-19 Novartis Ag Compositions and methods for selective protein expression
JP2017532019A (ja) * 2014-09-03 2017-11-02 バイオアトラ、エルエルシー 同じ真核細胞産生宿主における条件的活性型生物学的タンパク質の発見及び作製
WO2017186853A1 (en) * 2016-04-27 2017-11-02 Bcrt Holding Bv T cell-based bi-specific immunotherapeutics
WO2017193107A2 (en) 2016-05-06 2017-11-09 Juno Therapeutics, Inc. Genetically engineered cells and methods of making the same
JP2017533707A (ja) * 2014-10-31 2017-11-16 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア Ｔ細胞を刺激および拡大する組成物および方法
WO2017205846A1 (en) 2016-05-27 2017-11-30 Aadigen, Llc Peptides and nanoparticles for intracellular delivery of genome-editing molecules
WO2017214207A2 (en) 2016-06-06 2017-12-14 Juno Therapeutics, Inc. Methods for the treatment of b cell malignancies using adoptive cell therapy
WO2018005559A1 (en) 2016-06-27 2018-01-04 Juno Therapeutics, Inc. Method of identifying peptide epitopes, molecules that bind such epitopes and related uses
WO2018005556A1 (en) 2016-06-27 2018-01-04 Juno Therapeutics, Inc. Mhc-e restricted epitopes, binding molecules and related methods and uses
WO2018023094A1 (en) 2016-07-29 2018-02-01 Juno Therapeutics, Inc. Methods for assessing the presence or absence of replication competent virus
WO2018023093A1 (en) 2016-07-29 2018-02-01 Juno Therapeutics, Inc. Immunomodulatory polypeptides and related compositions and methods
WO2018023100A2 (en) 2016-07-29 2018-02-01 Juno Therapeutics, Inc. Anti-idiotypic antibodies and related methods
WO2018026819A2 (en) 2016-08-01 2018-02-08 Novartis Ag Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule
JP2018504894A (ja) * 2014-12-19 2018-02-22 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド キメラ抗原受容体およびその使用方法
WO2018049420A1 (en) 2016-09-12 2018-03-15 Juno Therapeutics, Inc. Perfusion bioreactor bag assemblies
CN107841506A (zh) * 2016-09-20 2018-03-27 上海恒润达生生物科技有限公司 靶向间皮素的嵌合抗原受体及其用途
CN107849112A (zh) * 2015-06-25 2018-03-27 美商生物细胞基因治疗有限公司 嵌合抗原受体(car)、组合物及其使用方法
WO2018063985A1 (en) 2016-09-28 2018-04-05 Atossa Genetics Inc. Methods of adoptive cell therapy
WO2018064681A1 (en) * 2016-09-30 2018-04-05 Poseida Therapeutics, Inc. Modified stem cell memory t cells, methods of making and methods of using same
WO2018067618A1 (en) 2016-10-03 2018-04-12 Juno Therapeutics, Inc. Hpv-specific binding molecules
WO2018071873A2 (en) 2016-10-13 2018-04-19 Juno Therapeutics, Inc. Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators
WO2018085731A2 (en) 2016-11-03 2018-05-11 Juno Therapeutics, Inc. Combination therapy of a t cell therapy and a btk inhibitor
CN108034669A (zh) * 2017-11-17 2018-05-15 山东兴瑞生物科技有限公司 一种抗vegf基因、及利用其修饰的t细胞、制备方法和应用
US9975960B2 (en) 2014-05-09 2018-05-22 Samsung Electronics Co., Ltd. Anti-HER2 antibody and anti-c-Met/anti-HER2 bispecific antibodies comprising the same
WO2018071913A3 (en) * 2016-10-14 2018-05-24 Dana-Farber Cancer Institute, Inc. Modular tetravalent bispecific antibody platform
WO2018093591A1 (en) 2016-11-03 2018-05-24 Juno Therapeutics, Inc. Combination therapy of a cell based therapy and a microglia inhibitor
WO2018102787A1 (en) 2016-12-03 2018-06-07 Juno Therapeutics, Inc. Methods for determining car-t cells dosing
WO2018102786A1 (en) 2016-12-03 2018-06-07 Juno Therapeutics, Inc. Methods for modulation of car-t cells
WO2018102785A2 (en) 2016-12-03 2018-06-07 Juno Therapeutics, Inc. Methods and compositions for use of therapeutic t cells in combination with kinase inhibitors
WO2018106732A1 (en) 2016-12-05 2018-06-14 Juno Therapeutics, Inc. Production of engineered cells for adoptive cell therapy
CN108174604A (zh) * 2015-08-07 2018-06-15 西雅图儿童医院（Dba西雅图儿童研究所） 用于实体瘤靶向的双特异性car t细胞
WO2018111340A1 (en) 2016-12-16 2018-06-21 Novartis Ag Methods for determining potency and proliferative function of chimeric antigen receptor (car)-t cells
CN108219004A (zh) * 2018-02-08 2018-06-29 吉林省拓华生物科技有限公司 双特异嵌合抗原受体修饰的t细胞、其制备方法及用途
WO2018121604A1 (zh) * 2016-12-29 2018-07-05 天津天锐生物科技有限公司 一种多靶点嵌合抗原受体
CN108251392A (zh) * 2018-03-30 2018-07-06 广东溢多利生物科技股份有限公司 提高比活和热稳定性的葡萄糖氧化酶突变体及其编码基因和应用
CN108264566A (zh) * 2016-12-30 2018-07-10 上海欣百诺生物科技有限公司 一种融合抗cd3抗体结构域和t细胞正共刺激分子配体的双特异性分子及其应用
CN108285486A (zh) * 2018-01-15 2018-07-17 浙江阿思科力生物科技有限公司 以cd20为靶点的特异性抗体、car-nk细胞及其制备和应用
WO2018132518A1 (en) 2017-01-10 2018-07-19 Juno Therapeutics, Inc. Epigenetic analysis of cell therapy and related methods
WO2018134691A2 (en) 2017-01-20 2018-07-26 Juno Therapeutics Gmbh Cell surface conjugates and related cell compositions and methods
WO2018140725A1 (en) 2017-01-26 2018-08-02 Novartis Ag Cd28 compositions and methods for chimeric antigen receptor therapy
WO2018144535A1 (en) 2017-01-31 2018-08-09 Novartis Ag Treatment of cancer using chimeric t cell receptor proteins having multiple specificities
WO2018157171A2 (en) 2017-02-27 2018-08-30 Juno Therapeutics, Inc. Compositions, articles of manufacture and methods related to dosing in cell therapy
WO2018160731A1 (en) 2017-02-28 2018-09-07 Novartis Ag Shp inhibitor compositions and uses for chimeric antigen receptor therapy
WO2018170188A2 (en) 2017-03-14 2018-09-20 Juno Therapeutics, Inc. Methods for cryogenic storage
WO2018178055A1 (en) * 2017-03-29 2018-10-04 F. Hoffmann-La Roche Ag Bispecific antigen binding molecule for a costimulatory tnf receptor
WO2018178377A1 (en) 2017-03-31 2018-10-04 Cellectis Sa Universal anti-cd22 chimeric antigen receptor engineered immune cells
WO2018178076A1 (en) * 2017-03-29 2018-10-04 F. Hoffmann-La Roche Ag Bispecific antigen binding molecule for a costimulatory tnf receptor
WO2018187791A1 (en) 2017-04-07 2018-10-11 Juno Therapeutics, Inc Engineered cells expressing prostate-specific membrane antigen (psma) or a modified form thereof and related methods
WO2018191723A1 (en) 2017-04-14 2018-10-18 Juno Therapeutics, Inc. Methods for assessing cell surface glycosylation
WO2018195175A1 (en) 2017-04-18 2018-10-25 FUJIFILM Cellular Dynamics, Inc. Antigen-specific immune effector cells
WO2018197949A1 (en) 2017-04-27 2018-11-01 Juno Therapeutics Gmbh Oligomeric particle reagents and methods of use thereof
WO2018200562A1 (en) * 2017-04-24 2018-11-01 Memorial Sloan Kettering Cancer Center Anti-cd33 antibody agents
CN108728458A (zh) * 2017-04-21 2018-11-02 上海恒润达生生物科技有限公司 靶向mesothelin的嵌合抗原受体并联合表达IL-15的方法和用途
WO2018204427A1 (en) 2017-05-01 2018-11-08 Juno Therapeutics, Inc. Combination of a cell therapy and an immunomodulatory compound
KR20180127403A (ko) 2016-03-17 2018-11-28 고쿠리츠다이가쿠호우진 야마구치 다이가쿠 면역 기능 제어 인자를 발현하는 면역 담당 세포 및 발현 벡터
WO2018223101A1 (en) 2017-06-02 2018-12-06 Juno Therapeutics, Inc. Articles of manufacture and methods for treatment using adoptive cell therapy
WO2018223098A1 (en) 2017-06-02 2018-12-06 Juno Therapeutics, Inc. Articles of manufacture and methods related to toxicity associated with cell therapy
WO2018229715A1 (en) 2017-06-16 2018-12-20 Novartis Ag Compositions comprising anti-cd32b antibodies and methods of use thereof
WO2018234370A1 (en) 2017-06-20 2018-12-27 Institut Curie Immune cells defective for suv39h1
WO2019006427A1 (en) 2017-06-29 2019-01-03 Juno Therapeutics, Inc. WALL MODEL FOR ASSESSING TOXICITIES ASSOCIATED WITH IMMUNOTHERAPIES
CN109153731A (zh) * 2016-08-10 2019-01-04 南京传奇生物科技有限公司 靶向bcma的嵌合抗原受体及其使用方法
US10174095B2 (en) 2014-07-21 2019-01-08 Novartis Ag Nucleic acid encoding a humanized anti-BCMA chimeric antigen receptor
WO2019014891A1 (zh) * 2017-07-20 2019-01-24 深圳普瑞金生物药业有限公司 一种用于治疗肿瘤的egfr单域抗体cart及其应用
CN109293781A (zh) * 2018-09-12 2019-02-01 中国人民解放军总医院 嵌合抗原受体及其基因和重组表达载体、cd19-cd20双靶向性的t细胞及其应用
WO2019028051A1 (en) * 2017-07-31 2019-02-07 Lentigen Technology, Inc. COMPOSITIONS AND METHODS FOR TREATING CANCER BY ANTI-CD19 / CD20 IMMUNOTHERAPY
WO2019027850A1 (en) 2017-07-29 2019-02-07 Juno Therapeutics, Inc. CELL EXPANSION REAGENTS EXPRESSING RECOMBINANT RECEPTORS
WO2019032929A1 (en) 2017-08-09 2019-02-14 Juno Therapeutics, Inc. METHODS AND COMPOSITIONS FOR PREPARING GENETICALLY MODIFIED CELLS
WO2019032927A1 (en) 2017-08-09 2019-02-14 Juno Therapeutics, Inc. METHODS FOR PRODUCING GENETICALLY MODIFIED CELL COMPOSITIONS AND COMPOSITIONS THEREOF
WO2019046832A1 (en) 2017-09-01 2019-03-07 Juno Therapeutics, Inc. GENE EXPRESSION AND EVALUATION OF RISK OF DEVELOPMENT OF TOXICITY FOLLOWING CELL THERAPY
WO2019051335A1 (en) 2017-09-07 2019-03-14 Juno Therapeutics, Inc. METHODS OF IDENTIFYING CELLULAR CHARACTERISTICS RELATED TO RESPONSES ASSOCIATED WITH CELL THERAPY
WO2019057102A1 (en) 2017-09-20 2019-03-28 Tsinghua University HPK1 TARGETING ARNG AND HPK1 GENE EDITING METHOD
WO2019070856A1 (en) * 2017-10-03 2019-04-11 Precision Biosciences, Inc. MODIFIED EPIDERMAL GROWTH FACTOR RECEPTOR PEPTIDES FOR USE IN GENETICALLY MODIFIED CELLS
WO2019070541A1 (en) 2017-10-03 2019-04-11 Juno Therapeutics, Inc. HPV-SPECIFIC BINDING MOLECULES
EP3328994A4 (en) * 2015-07-31 2019-04-17 Memorial Sloan-Kettering Cancer Center CD56-Faced Antigen-Binding Proteins and Uses Thereof
WO2019073973A1 (ja) 2017-10-10 2019-04-18 国立大学法人山口大学 メモリー機能を有するｔ細胞又はｂ細胞の増強剤、悪性腫瘍再発抑制剤、及びｔ細胞又はｂ細胞にメモリー機能を誘導する誘導剤
WO2019079569A1 (en) 2017-10-18 2019-04-25 Novartis Ag COMPOSITIONS AND METHODS FOR SELECTIVE DEGRADATION OF A PROTEIN
WO2019084288A1 (en) 2017-10-25 2019-05-02 Novartis Ag METHODS FOR DESIGNING CHIMERIC ANTIGENIC RECEPTOR EXPRESSION CELLS
WO2019081983A1 (en) 2017-10-25 2019-05-02 Novartis Ag CD32B TARGETING ANTIBODIES AND METHODS OF USE
WO2019089798A1 (en) 2017-10-31 2019-05-09 Novartis Ag Anti-car compositions and methods
WO2019090003A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Chimeric antigen receptors specific for b-cell maturation antigen (bcma)
WO2019089848A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Methods associated with tumor burden for assessing response to a cell therapy
WO2019090364A1 (en) 2017-11-06 2019-05-09 Juno Therapeutics, Inc. Combination of a cell therapy and a gamma secretase inhibitor
WO2019090004A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Process for producing a t cell composition
WO2019089858A2 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Methods of assessing or monitoring a response to a cell therapy
WO2019089855A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Process for generating therapeutic compositions of engineered cells
WO2019089884A2 (en) 2017-11-01 2019-05-09 Editas Medicine, Inc. Methods, compositions and components for crispr-cas9 editing of tgfbr2 in t cells for immunotherapy
WO2019089982A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Method of assessing activity of recombinant antigen receptors
WO2019089969A2 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for b-cell maturation antigen
WO2019090202A1 (en) 2017-11-06 2019-05-09 Editas Medicine, Inc. Methods, compositions and components for crispr-cas9 editing of cblb in t cells for immunotherapy
WO2019094835A1 (en) 2017-11-10 2019-05-16 Juno Therapeutics, Inc. Closed-system cryogenic vessels
WO2019094482A1 (en) * 2017-11-10 2019-05-16 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting tumor antigens
WO2019109053A1 (en) 2017-12-01 2019-06-06 Juno Therapeutics, Inc. Methods for dosing and for modulation of genetically engineered cells
WO2019113557A1 (en) 2017-12-08 2019-06-13 Juno Therapeutics, Inc. Process for producing a composition of engineered t cells
WO2019113556A1 (en) 2017-12-08 2019-06-13 Juno Therapeutics, Inc. Serum-free media formulation for culturing cells and methods of use thereof
WO2019113559A2 (en) 2017-12-08 2019-06-13 Juno Therapeutics, Inc. Phenotypic markers for cell therapy and related methods
WO2019118937A1 (en) 2017-12-15 2019-06-20 Juno Therapeutics, Inc. Anti-cct5 binding molecules and methods of use thereof
US10329543B2 (en) 2017-10-23 2019-06-25 Poseida Therapeutics, Inc. Modified stem cell memory T cells, methods of making and methods of using same
WO2019129220A1 (en) * 2017-12-28 2019-07-04 Nanjing Legend Biotech Co., Ltd. Multispecific chimeric receptors comprising nkg2d domain and methods of use thereof
KR20190092285A (ko) * 2018-01-29 2019-08-07 (주)에스엠티바이오 췌장 또는 담관계암 치료를 위한 키메라 항원 수용체
WO2019152743A1 (en) 2018-01-31 2019-08-08 Celgene Corporation Combination therapy using adoptive cell therapy and checkpoint inhibitor
WO2019152747A1 (en) 2018-01-31 2019-08-08 Juno Therapeutics, Inc. Methods and reagents for assessing the presence or absence of replication competent virus
WO2019170845A1 (en) 2018-03-09 2019-09-12 Ospedale San Raffaele S.R.L. Il-1 antagonist and toxicity induced by cell therapy
US10415016B2 (en) 2016-09-30 2019-09-17 Poseida Therapeutics, Inc. Modified stem cell memory T cells, methods of making and methods of using same
WO2019195486A1 (en) 2018-04-05 2019-10-10 Juno Therapeutics, Inc. T cell receptors and engineered cells expressing same
WO2019195586A1 (en) 2018-04-06 2019-10-10 The Regents Of The University Of California Methods of treating egfrviii expressing glioblastomas
WO2019195492A1 (en) 2018-04-05 2019-10-10 Juno Therapeutics, Inc. Methods of producing cells expressing a recombinant receptor and related compositions
WO2019195596A1 (en) 2018-04-06 2019-10-10 The Regents Of The University Of California Methods of treating glioblastomas
WO2019210153A1 (en) 2018-04-27 2019-10-31 Novartis Ag Car t cell therapies with enhanced efficacy
CN110402255A (zh) * 2017-04-04 2019-11-01 豪夫迈·罗氏有限公司 新颖的能够特异性结合cd40和fap的双特异性抗原结合分子
WO2019213282A1 (en) 2018-05-01 2019-11-07 Novartis Ag Biomarkers for evaluating car-t cells to predict clinical outcome
WO2019213184A1 (en) 2018-05-03 2019-11-07 Juno Therapeutics, Inc. Combination therapy of a chimeric antigen receptor (car) t cell therapy and a kinase inhibitor
WO2019227003A1 (en) 2018-05-25 2019-11-28 Novartis Ag Combination therapy with chimeric antigen receptor (car) therapies
WO2019237035A1 (en) 2018-06-08 2019-12-12 Intellia Therapeutics, Inc. Compositions and methods for immunooncology
US10525083B2 (en) 2016-10-07 2020-01-07 Novartis Ag Nucleic acid molecules encoding chimeric antigen receptors comprising a CD20 binding domain
WO2020012337A1 (en) 2018-07-10 2020-01-16 Novartis Ag 3-(5-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and their use in the treatment of i karos family zinc finger 2 (ikzf2)-dependent diseases
WO2020011247A1 (en) 2018-07-13 2020-01-16 Nanjing Legend Biotech Co., Ltd. Co-receptor systems for treating infectious diseases
WO2020033927A2 (en) 2018-08-09 2020-02-13 Juno Therapeutics, Inc. Processes for generating engineered cells and compositions thereof
WO2020033916A1 (en) 2018-08-09 2020-02-13 Juno Therapeutics, Inc. Methods for assessing integrated nucleic acids
US10568947B2 (en) 2014-07-21 2020-02-25 Novartis Ag Treatment of cancer using a CLL-1 chimeric antigen receptor
WO2020056047A1 (en) 2018-09-11 2020-03-19 Juno Therapeutics, Inc. Methods for mass spectrometry analysis of engineered cell compositions
CN110997920A (zh) * 2017-06-07 2020-04-10 英特拉克森公司 新型细胞标签的表达
US10640562B2 (en) 2018-07-17 2020-05-05 Mcmaster University T cell-antigen coupler with various construct optimizations
WO2020089343A1 (en) 2018-10-31 2020-05-07 Juno Therapeutics Gmbh Methods for selection and stimulation of cells and apparatus for same
WO2020092848A2 (en) 2018-11-01 2020-05-07 Juno Therapeutics, Inc. Methods for treatment using chimeric antigen receptors specific for b-cell maturation antigen
US10647778B2 (en) 2015-02-09 2020-05-12 University Of Florida Research Foundation, Incorporated Bi-specific chimeric antigen receptor and uses thereof
WO2020097403A1 (en) 2018-11-08 2020-05-14 Juno Therapeutics, Inc. Methods and combinations for treatment and t cell modulation
WO2020097132A1 (en) 2018-11-06 2020-05-14 Juno Therapeutics, Inc. Process for producing genetically engineered t cells
US10654931B2 (en) 2015-08-11 2020-05-19 Osaka University Antibody
WO2020102770A1 (en) 2018-11-16 2020-05-22 Juno Therapeutics, Inc. Methods of dosing engineered t cells for the treatment of b cell malignancies
WO2020106621A1 (en) 2018-11-19 2020-05-28 Board Of Regents, The University Of Texas System A modular, polycistronic vector for car and tcr transduction
WO2020112493A1 (en) 2018-11-29 2020-06-04 Board Of Regents, The University Of Texas System Methods for ex vivo expansion of natural killer cells and use thereof
WO2020113188A2 (en) 2018-11-30 2020-06-04 Juno Therapeutics, Inc. Methods for dosing and treatment of b cell malignancies in adoptive cell therapy
WO2020113029A2 (en) 2018-11-28 2020-06-04 Board Of Regents, The University Of Texas System Multiplex genome editing of immune cells to enhance functionality and resistance to suppressive environment
WO2020113194A2 (en) 2018-11-30 2020-06-04 Juno Therapeutics, Inc. Methods for treatment using adoptive cell therapy
WO2020128972A1 (en) 2018-12-20 2020-06-25 Novartis Ag Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives
JP2020099326A (ja) * 2019-12-27 2020-07-02 カースゲン セラピューティクス リミテッドＣａｒｓｇｅｎ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ キメラ抗原受容体タンパク質をコードする核酸およびキメラ抗原受容体タンパク質を発現するｔリンパ球
WO2020160050A1 (en) 2019-01-29 2020-08-06 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for receptor tyrosine kinase like orphan receptor 1 (ror1)
US10738278B2 (en) 2014-07-15 2020-08-11 Juno Therapeutics, Inc. Engineered cells for adoptive cell therapy
US10736918B2 (en) 2012-08-20 2020-08-11 Fred Hutchinson Cancer Research Center Method and compositions for cellular immunotherapy
US10738116B2 (en) 2015-03-19 2020-08-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Dual specific anti-CD22-anti-CD19 chimeric antigen receptors
EP3694872A1 (en) 2017-10-12 2020-08-19 Board Of Regents, The University Of Texas System T cell receptors for immunotherapy
WO2020165833A1 (en) 2019-02-15 2020-08-20 Novartis Ag 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2020165834A1 (en) 2019-02-15 2020-08-20 Novartis Ag Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
US10752684B2 (en) 2014-07-29 2020-08-25 Cellectis ROR1 (NTRKR1) specific chimeric antigen receptors for cancer immunotherapy
EP3169703B1 (en) 2014-07-16 2020-09-02 Hinrich Abken Chimeric antigen receptor and its use
US20200277400A1 (en) * 2015-05-15 2020-09-03 City Of Hope Chimeric antigen receptor compositions
US10786533B2 (en) 2015-07-15 2020-09-29 Juno Therapeutics, Inc. Engineered cells for adoptive cell therapy
JP2020156482A (ja) * 2014-03-19 2020-10-01 セレクティスＣｅｌｌｅｃｔｉｓ 癌免疫治療のためのｃｄ１２３特異的キメラ抗原受容体
US20200318069A1 (en) * 2014-09-19 2020-10-08 City Of Hope COSTIMULATORY CHIMERIC ANTIGEN RECEPTOR T CELLS TARGETING IL13R-alpha-2
US10800828B2 (en) 2015-03-26 2020-10-13 The Scripps Research Institute Switchable non-scFv chimeric receptors, switches, and methods of use thereof to treat cancer
WO2020219742A1 (en) 2019-04-24 2020-10-29 Novartis Ag Compositions and methods for selective protein degradation
WO2020223571A1 (en) 2019-05-01 2020-11-05 Juno Therapeutics, Inc. Cells expressing a chimeric receptor from a modified cd247 locus, related polynucleotides and methods
WO2020223535A1 (en) 2019-05-01 2020-11-05 Juno Therapeutics, Inc. Cells expressing a recombinant receptor from a modified tgfbr2 locus, related polynucleotides and methods
WO2020228825A1 (en) * 2019-05-16 2020-11-19 Nanjing Legend Biotech Co., Ltd. Engineered immune cells comprsing a recognition molecule
US20200360432A1 (en) * 2017-11-24 2020-11-19 Autolus Limited Polypeptide
WO2020247832A1 (en) 2019-06-07 2020-12-10 Juno Therapeutics, Inc. Automated t cell culture
CN112074534A (zh) * 2017-12-22 2020-12-11 阿尔麦克探索有限公司 双特异性抗原结合分子
WO2020252218A1 (en) 2019-06-12 2020-12-17 Juno Therapeutics, Inc. Combination therapy of a cell-mediated cytotoxic therapy and an inhibitor of a prosurvival bcl2 family protein
WO2021013950A1 (en) 2019-07-23 2021-01-28 Mnemo Therapeutics Immune cells defective for suv39h1
WO2021035194A1 (en) 2019-08-22 2021-02-25 Juno Therapeutics, Inc. Combination therapy of a t cell therapy and an enhancer of zeste homolog 2 (ezh2) inhibitor and related methods
US20210054346A1 (en) * 2015-02-24 2021-02-25 Board Of Regents, The University Of Texas System Selection methods for genetically-modified t cells
WO2021041994A2 (en) 2019-08-30 2021-03-04 Juno Therapeutics, Inc. Machine learning methods for classifying cells
WO2021043804A1 (en) 2019-09-02 2021-03-11 Institut Curie Immunotherapy targeting tumor neoantigenic peptides
WO2021050601A1 (en) 2019-09-09 2021-03-18 Scribe Therapeutics Inc. Compositions and methods for use in immunotherapy
US20210077532A1 (en) * 2018-04-17 2021-03-18 Innovative Cellular Therapeutics CO., LTD. Modified Cell Expansion and Uses Thereof
US10967005B2 (en) 2013-03-15 2021-04-06 Celgene Corporation Modified T lymphocytes comprising a BAFF antibody-inducible caspase and methods of apoptosis
WO2021078910A1 (en) 2019-10-22 2021-04-29 Institut Curie Immunotherapy targeting tumor neoantigenic peptides
WO2021084050A1 (en) 2019-10-30 2021-05-06 Juno Therapeutics Gmbh Cell selection and/or stimulation devices and methods of use
WO2021092498A1 (en) 2019-11-07 2021-05-14 Juno Therapeutics, Inc. Combination of a t cell therapy and (s)-3-[4-(4-morpholin-4 ylmethyl-benzyloxy)-l-oxo-l,3-dihydro-isoindol-2-yl]- piperidine-2,6-dione
US11008294B2 (en) 2017-10-30 2021-05-18 Neuropore Therapies, Inc. Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof
US11014989B2 (en) 2015-01-26 2021-05-25 Cellectis Anti-CLL1 specific single-chain chimeric antigen receptors (scCARs) for cancer immunotherapy
WO2021113770A1 (en) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Methods related to toxicity and response associated with cell therapy for treating b cell malignancies
WO2021113776A1 (en) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to bcma-targeted binding domains and related compositions and methods
WO2021113780A1 (en) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to gprc5d-targeted binding domains and related compositions and methods
WO2021123996A1 (en) 2019-12-20 2021-06-24 Novartis Ag Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases
WO2021146487A2 (en) 2020-01-14 2021-07-22 Synthekine, Inc. Il2 orthologs and methods of use
WO2021151008A1 (en) 2020-01-24 2021-07-29 Juno Therapuetics, Inc. Methods for dosing and treatment of follicular lymphoma and marginal zone lymphoma in adoptive cell therapy
US11077178B2 (en) * 2016-09-21 2021-08-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptor (CAR) that targets chemokine receptor CCR4 and its use
EP3858378A1 (en) * 2013-11-21 2021-08-04 Autolus Limited Cell
WO2021154887A1 (en) 2020-01-28 2021-08-05 Juno Therapeutics, Inc. Methods for t cell transduction
US11091546B2 (en) 2015-04-15 2021-08-17 The Scripps Research Institute Optimized PNE-based chimeric receptor T cell switches and uses thereof
WO2021163391A1 (en) 2020-02-12 2021-08-19 Juno Therapeutics, Inc. Cd19-directed chimeric antigen receptor t cell compositions and methods and uses thereof
WO2021163389A1 (en) 2020-02-12 2021-08-19 Juno Therapeutics, Inc. Bcma-directed chimeric antigen receptor t cell compositions and methods and uses thereof
WO2021167908A1 (en) 2020-02-17 2021-08-26 Board Of Regents, The University Of Texas System Methods for expansion of tumor infiltrating lymphocytes and use thereof
WO2021173995A2 (en) 2020-02-27 2021-09-02 Novartis Ag Methods of making chimeric antigen receptor-expressing cells
US11110123B2 (en) 2018-07-17 2021-09-07 Triumvira Immunologics Usa, Inc. T cell-antigen coupler with various construct optimizations
US11111288B2 (en) 2014-08-28 2021-09-07 Bioatla, Inc. Conditionally active chimeric antigen receptors for modified t-cells
US11130820B2 (en) 2012-12-20 2021-09-28 Celgene Corporation Chimeric antigen receptors
US20210309717A1 (en) * 2020-03-20 2021-10-07 Lyell Immunopharma, Inc. Novel Recombinant Cell Surface Markers
WO2021207689A2 (en) 2020-04-10 2021-10-14 Juno Therapeutics, Inc. Methods and uses related to cell therapy engineered with a chimeric antigen receptor targeting b-cell maturation antigen
EP3737688A4 (en) * 2018-01-10 2021-11-03 The General Hospital Corporation IMMUNE CELLS EXPRESSING A CHEMICAL ANTIGENIC RECEPTOR
US11174306B2 (en) 2016-10-19 2021-11-16 The Scripps Research Institute Chimeric antigen receptor effector cell switches with humanized targeting moieties and/or optimized chimeric antigen receptor interacting domains and uses thereof
WO2021228999A1 (en) 2020-05-12 2021-11-18 Institut Curie Neoantigenic epitopes associated with sf3b1 mutations
WO2021231657A1 (en) 2020-05-13 2021-11-18 Juno Therapeutics, Inc. Methods of identifying features associated with clinical response and uses thereof
WO2021231661A2 (en) 2020-05-13 2021-11-18 Juno Therapeutics, Inc. Process for producing donor-batched cells expressing a recombinant receptor
WO2021237068A2 (en) 2020-05-21 2021-11-25 Board Of Regents, The University Of Texas System T cell receptors with vgll1 specificity and uses thereof
JP2021180686A (ja) * 2014-04-23 2021-11-25 ジュノー セラピューティクス インコーポレイテッド 養子療法用の免疫細胞集団を単離、培養、および遺伝子操作するための方法
US11198737B2 (en) 2017-10-12 2021-12-14 Mcmaster University T cell-antigen coupler with Y177 mutation and methods of uses thereof
WO2021252920A1 (en) 2020-06-11 2021-12-16 Novartis Ag Zbtb32 inhibitors and uses thereof
EA039192B1 (ru) * 2015-03-30 2021-12-16 Селджин Корпорейшн Способ лечения рака и набор для лечения рака
WO2021260186A1 (en) 2020-06-26 2021-12-30 Juno Therapeutics Gmbh Engineered t cells conditionally expressing a recombinant receptor, related polynucleotides and methods
WO2021260528A1 (en) 2020-06-23 2021-12-30 Novartis Ag Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives
WO2022023576A1 (en) 2020-07-30 2022-02-03 Institut Curie Immune cells defective for socs1
WO2022029573A1 (en) 2020-08-03 2022-02-10 Novartis Ag Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2022029660A1 (en) 2020-08-05 2022-02-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to ror1-targeted binding domains and related compositions and methods
US11248058B2 (en) 2015-02-19 2022-02-15 University Of Florida Research Foundation, Inc. Chimeric antigen receptors and uses thereof
US11325948B2 (en) 2016-03-19 2022-05-10 Exuma Biotech Corp. Methods and compositions for genetically modifying lymphocytes to express polypeptides comprising the intracellular domain of MPL
US20220145325A1 (en) * 2019-03-08 2022-05-12 Autolus Limited Compositions and methods comprising engineered chimeric antigen receptor and modulator of car
WO2022104109A1 (en) 2020-11-13 2022-05-19 Catamaran Bio, Inc. Genetically modified natural killer cells and methods of use thereof
EP4011381A1 (en) 2016-06-03 2022-06-15 Memorial Sloan-Kettering Cancer Center Adoptive cell therapies as early treatment options
EP4012415A2 (en) 2015-12-04 2022-06-15 Juno Therapeutics, Inc. Methods and compositions related to toxicity associated with cell therapy
US11365262B2 (en) 2015-08-20 2022-06-21 Autolus Limited Cell
WO2022133030A1 (en) 2020-12-16 2022-06-23 Juno Therapeutics, Inc. Combination therapy of a cell therapy and a bcl2 inhibitor
JP2022093564A (ja) * 2014-04-23 2022-06-23 ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム キメラ抗原受容体（ｃａｒ）並びにその製造及び使用方法
US11384350B2 (en) 2014-12-15 2022-07-12 The Regents Of The University Of California Cytotoxic molecules responsive to intracellular ligands for selective T cell mediated killing
WO2022150731A1 (en) 2021-01-11 2022-07-14 Sana Biotechnology, Inc. Use of cd8-targeted viral vectors
WO2022156786A1 (zh) * 2021-01-22 2022-07-28 南京助天中科科技发展有限公司 一种嵌合抗原受体改造的nk细胞及其制备方法与应用
WO2022166665A1 (zh) * 2021-02-08 2022-08-11 浙江大学 一种以内源性蛋白质分子替代单结构域抗体的嵌合抗原受体
EP3887509A4 (en) * 2018-11-30 2022-08-31 Dana-Farber Cancer Institute, Inc. CHIMERA ANTIGEN RECEPTOR AND METHODS OF USING THE SAME
WO2022187406A1 (en) 2021-03-03 2022-09-09 Juno Therapeutics, Inc. Combination of a t cell therapy and a dgk inhibitor
WO2022189626A2 (en) 2021-03-11 2022-09-15 Mnemo Therapeutics Tumor neoantigenic peptides
WO2022189620A1 (en) 2021-03-11 2022-09-15 Institut Curie Transmembrane neoantigenic peptides
WO2022189639A1 (en) 2021-03-11 2022-09-15 Mnemo Therapeutics Tumor neoantigenic peptides and uses thereof
US11453723B1 (en) 2021-06-25 2022-09-27 Mcmaster University BCMA T cell-antigen couplers and uses thereof
WO2022204071A1 (en) 2021-03-22 2022-09-29 Juno Therapeutics, Inc. Method to assess potency of viral vector particles
WO2022204070A1 (en) 2021-03-22 2022-09-29 Juno Therapeutics, Inc. Methods of determining potency of a therapeutic cell composition
US20220306719A1 (en) * 2019-06-19 2022-09-29 Julius-Maximilians-Universität Würzburg Ultramodular igg3-based spacer domain and multi-function site for implementation in chimeric antigen receptor design
WO2022212400A1 (en) 2021-03-29 2022-10-06 Juno Therapeutics, Inc. Methods for dosing and treatment with a combination of a checkpoint inhibitor therapy and a car t cell therapy
WO2022212384A1 (en) 2021-03-29 2022-10-06 Juno Therapeutics, Inc. Combination of a car t cell therapy and an immunomodulatory compound for treatment of lymphoma
WO2022215011A1 (en) 2021-04-07 2022-10-13 Novartis Ag USES OF ANTI-TGFβ ANTIBODIES AND OTHER THERAPEUTIC AGENTS FOR THE TREATMENT OF PROLIFERATIVE DISEASES
WO2022229853A1 (en) 2021-04-27 2022-11-03 Novartis Ag Viral vector production system
WO2022234009A2 (en) 2021-05-06 2022-11-10 Juno Therapeutics Gmbh Methods for stimulating and transducing t cells
EP3920952A4 (en) * 2019-02-08 2023-01-25 Seattle Children's Hospital (DBA Seattle Children's Research Institute) CHIMERIC CYTOKINE RECEPTORS
WO2023015217A1 (en) 2021-08-04 2023-02-09 Sana Biotechnology, Inc. Use of cd4-targeted viral vectors
WO2023014922A1 (en) 2021-08-04 2023-02-09 The Regents Of The University Of Colorado, A Body Corporate Lat activating chimeric antigen receptor t cells and methods of use thereof
WO2023017544A1 (en) * 2021-08-12 2023-02-16 Cellogen Therapeutics Pvt. Ltd. Chimeric antigen receptors (car) for b cell malignancies
CN108137669B (zh) * 2015-05-18 2023-02-17 优瑞科生物技术公司 抗ror1嵌合抗原受体
WO2023037125A1 (en) 2021-09-10 2023-03-16 Ucl Business Ltd Binding domain
RU2792042C2 (ru) * 2015-10-07 2023-03-16 Бионтэк Селл & Гене Терапиез Гмбх Антигенные рецепторы и их применения
US11634498B2 (en) 2016-04-29 2023-04-25 University Of Florida Research Foundation, Incorporated Chimeric antigen receptors and uses thereof
US11667723B2 (en) 2020-08-17 2023-06-06 Utc Therapeutics (Shanghai) Co., Ltd. Lymphocytes-antigen presenting cells co-stimulators and uses thereof
US11667715B2 (en) 2019-02-15 2023-06-06 University Of Southern California Lym-1 and Lym-2 antibody compositions and improved car constructs
WO2023105000A1 (en) 2021-12-09 2023-06-15 Zygosity Limited Vector
WO2023115039A2 (en) 2021-12-17 2023-06-22 Sana Biotechnology, Inc. Modified paramyxoviridae fusion glycoproteins
WO2023115041A1 (en) 2021-12-17 2023-06-22 Sana Biotechnology, Inc. Modified paramyxoviridae attachment glycoproteins
EP4200340A1 (en) 2020-08-21 2023-06-28 12343096 Canada Inc. Modular assembly receptors and uses thereof
WO2023126458A1 (en) 2021-12-28 2023-07-06 Mnemo Therapeutics Immune cells with inactivated suv39h1 and modified tcr
US11701384B2 (en) 2016-09-02 2023-07-18 The Regents Of The University Of California Methods and compositions involving interleukin-6 receptor alpha-binding single chain variable fragments
WO2023139269A1 (en) 2022-01-21 2023-07-27 Mnemo Therapeutics Modulation of suv39h1 expression by rnas
WO2023147515A1 (en) 2022-01-28 2023-08-03 Juno Therapeutics, Inc. Methods of manufacturing cellular compositions
WO2023150518A1 (en) 2022-02-01 2023-08-10 Sana Biotechnology, Inc. Cd3-targeted lentiviral vectors and uses thereof
US11725210B2 (en) 2017-03-17 2023-08-15 Fred Hutchinson Cancer Center Immunomodulatory fusion proteins and uses thereof
US11725060B2 (en) 2017-07-20 2023-08-15 Aptevo Reserch and Development LLC Antigen binding proteins binding to 5T4 and 4-1BB and related compositions and methods
US11753460B2 (en) 2016-12-13 2023-09-12 Seattle Children's Hospital Methods of exogenous drug activation of chemical-induced signaling complexes expressed in engineered cells in vitro and in vivo
US11759480B2 (en) 2017-02-28 2023-09-19 Endocyte, Inc. Compositions and methods for CAR T cell therapy
WO2023178348A1 (en) 2022-03-18 2023-09-21 The Regents Of The University Of Colorado, A Body Corporate Genetically engineered t-cell co-receptors and methods of use thereof
WO2023180552A1 (en) 2022-03-24 2023-09-28 Institut Curie Immunotherapy targeting tumor transposable element derived neoantigenic peptides in glioblastoma
WO2023193015A1 (en) 2022-04-01 2023-10-05 Sana Biotechnology, Inc. Cytokine receptor agonist and viral vector combination therapies
US11779602B2 (en) 2018-01-22 2023-10-10 Endocyte, Inc. Methods of use for CAR T cells
WO2023196933A1 (en) 2022-04-06 2023-10-12 The Regents Of The University Of Colorado, A Body Corporate Chimeric antigen receptor t cells and methods of use thereof
WO2023196921A1 (en) 2022-04-06 2023-10-12 The Regents Of The University Of Colorado, A Body Corporate Granzyme expressing t cells and methods of use
US11793834B2 (en) 2018-12-12 2023-10-24 Kite Pharma, Inc. Chimeric antigen and T cell receptors and methods of use
WO2023211972A1 (en) 2022-04-28 2023-11-02 Medical University Of South Carolina Chimeric antigen receptor modified regulatory t cells for treating cancer
WO2023213969A1 (en) 2022-05-05 2023-11-09 Juno Therapeutics Gmbh Viral-binding protein and related reagents, articles, and methods of use
WO2023214325A1 (en) 2022-05-05 2023-11-09 Novartis Ag Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors
WO2023220655A1 (en) 2022-05-11 2023-11-16 Celgene Corporation Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy
EP4279085A1 (en) 2022-05-20 2023-11-22 Mnemo Therapeutics Compositions and methods for treating a refractory or relapsed cancer or a chronic infectious disease
US11827889B2 (en) 2012-04-11 2023-11-28 The U.S.A., As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting B-cell maturation antigen
US11827904B2 (en) 2015-04-29 2023-11-28 Fred Hutchinson Cancer Center Modified stem cells and uses thereof
WO2023230581A1 (en) 2022-05-25 2023-11-30 Celgene Corporation Methods of manufacturing t cell therapies
US11845794B2 (en) 2013-05-03 2023-12-19 Ohio State Innovation Foundation CS1-specific chimeric antigen receptor engineered immune effector cells
US11845803B2 (en) 2017-02-17 2023-12-19 Fred Hutchinson Cancer Center Combination therapies for treatment of BCMA-related cancers and autoimmune disorders
WO2023250400A1 (en) 2022-06-22 2023-12-28 Juno Therapeutics, Inc. Treatment methods for second line therapy of cd19-targeted car t cells
WO2024006960A1 (en) 2022-06-29 2024-01-04 Juno Therapeutics, Inc. Lipid nanoparticles for delivery of nucleic acids
EP4302768A2 (en) 2017-06-22 2024-01-10 Board Of Regents, The University Of Texas System Methods for producing regulatory immune cells and uses thereof
US11879011B2 (en) 2016-05-13 2024-01-23 Bioatla, Inc. Anti-ROR2 antibodies, antibody fragments, their immunoconjucates and uses thereof
US11883432B2 (en) 2020-12-18 2024-01-30 Century Therapeutics, Inc. Chimeric antigen receptor system with adaptable receptor specificity
EP4326293A1 (en) 2021-04-22 2024-02-28 Baylor College of Medicine Methods of engineering immune cells having reduced fratricidal activity
WO2024044779A2 (en) 2022-08-26 2024-02-29 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for delta-like ligand 3 (dll3)
US11919937B2 (en) 2018-01-09 2024-03-05 Board Of Regents, The University Of Texas System T cell receptors for immunotherapy
WO2024054944A1 (en) 2022-09-08 2024-03-14 Juno Therapeutics, Inc. Combination of a t cell therapy and continuous or intermittent dgk inhibitor dosing
US11939389B2 (en) 2018-06-13 2024-03-26 Novartis Ag BCMA chimeric antigen receptors and uses thereof
WO2024062138A1 (en) 2022-09-23 2024-03-28 Mnemo Therapeutics Immune cells comprising a modified suv39h1 gene
WO2024081820A1 (en) 2022-10-13 2024-04-18 Sana Biotechnology, Inc. Viral particles targeting hematopoietic stem cells
WO2024089639A1 (en) 2022-10-26 2024-05-02 Novartis Ag Lentiviral formulations
US11975026B2 (en) 2019-11-26 2024-05-07 Novartis Ag CD19 and CD22 chimeric antigen receptors and uses thereof
US11980640B2 (en) 2017-05-15 2024-05-14 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Bicistronic chimeric antigen receptors and their uses
WO2024100604A1 (en) 2022-11-09 2024-05-16 Juno Therapeutics Gmbh Methods for manufacturing engineered immune cells
US11987804B2 (en) 2018-04-27 2024-05-21 Seattle Children's Hospital Rapamycin resistant cells
WO2024124132A1 (en) 2022-12-09 2024-06-13 Juno Therapeutics, Inc. Machine learning methods for predicting cell phenotype using holographic imaging
US12016923B2 (en) 2021-06-01 2024-06-25 Triumvira Immunologics Usa, Inc. Claudin 18.2 T cell-antigen couplers and uses thereof
US12024559B2 (en) 2020-10-23 2024-07-02 Asher Biotherapeutics, Inc. Fusions with CD8 antigen binding molecules for modulating immune cell function
US12043654B2 (en) 2020-06-02 2024-07-23 Innovative Cellular Therapeutics Holdings, Ltd. Anti-GCC antibody and CAR thereof for treating digestive system cancer
WO2024161021A1 (en) 2023-02-03 2024-08-08 Juno Therapeutics Gmbh Methods for non-viral manufacturing of engineered immune cells
US12076343B2 (en) 2020-02-19 2024-09-03 Innovative Cellular Therapeutics Holdings, Ltd. Engineered safety in cell therapy
WO2024182516A1 (en) 2023-02-28 2024-09-06 Juno Therapeutics, Inc. Cell therapy for treating systemic autoimmune diseases
US12102652B2 (en) 2016-08-26 2024-10-01 Baylor College Of Medicine Constitutively active cytokine receptors for cell therapy
US12122820B2 (en) 2015-09-22 2024-10-22 The Trustees Of The University Of Pennsylvania Method of redirecting t cells to treat HIV infection
WO2024220560A1 (en) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Engineered protein g fusogens and related lipid particles and methods thereof
WO2024220598A2 (en) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Lentiviral vectors with two or more genomes
WO2024220588A1 (en) 2023-04-18 2024-10-24 Juno Therapeutics, Inc. Cytotoxicity assay for assessing potency of therapeutic cell compositions
WO2024220574A1 (en) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Universal protein g fusogens and adapter systems thereof and related lipid particles and uses
WO2024226858A1 (en) 2023-04-26 2024-10-31 Juno Therapeutics, Inc. Methods for viral vector manufacturing
US12144827B2 (en) 2021-02-25 2024-11-19 Lyell Immunopharma, Inc. ROR1 targeting chimeric antigen receptor
US12144850B2 (en) 2016-04-08 2024-11-19 Purdue Research Foundation Methods and compositions for car T cell therapy
US12150981B2 (en) 2012-12-20 2024-11-26 Purdue Research Foundation Chimeric antigen receptor-expressing T cells as anti-cancer therapeutics
WO2024243365A2 (en) 2023-05-23 2024-11-28 Juno Therapeutics, Inc. Activation markers of t cells and method for assessing t cell activation
WO2024243441A1 (en) 2023-05-24 2024-11-28 Kumquat Biosciences Inc. Heterocyclic compounds and uses thereof
US12161668B2 (en) 2017-01-10 2024-12-10 The General Hospital Corporation T cells expressing a chimeric antigen receptor
US12240915B2 (en) 2018-08-30 2025-03-04 Innovative Cellular Therapeutics Holdings, Ltd. Chimeric antigen receptor cells for treating solid tumor
US12240870B2 (en) 2018-02-23 2025-03-04 Purdue Research Foundation Sequencing method for CAR T cell therapy
EP4520334A1 (en) 2023-09-07 2025-03-12 Mnemo Therapeutics Methods and compositions for improving immune response
WO2025052001A1 (en) 2023-09-07 2025-03-13 Mnemo Therapeutics Methods and compositions for improving immune response
WO2025054202A1 (en) 2023-09-05 2025-03-13 Sana Biotechnology, Inc. Method of screening a sample comprising a transgene with a unique barcode
US12258574B2 (en) 2016-03-19 2025-03-25 Exuma Biotech Corp. Methods and compositions for transducing lymphocytes and regulating the activity thereof
EP4240831A4 (en) * 2020-11-04 2025-03-26 Fate Therapeutics, Inc. Engineered ipsc and persistent immune effector cells
US12275787B2 (en) 2017-06-21 2025-04-15 Icell Gene Therapeutics Llc Chimeric antigen receptors (CARs), compositions and methods thereof
WO2025082603A1 (en) 2023-10-18 2025-04-24 Institut Curie Engineered immune cells overexpressing cd74 molecule
WO2025096975A1 (en) 2023-11-02 2025-05-08 The Regents Of The University Of Colorado, A Body Corporate Compositions and methods of enhancing immune cell therapies by runx2 modulation
US12311022B2 (en) 2023-03-31 2025-05-27 AbelZeta Inc. Bispecific chimeric antigen receptors targeting CD20 and BCMA
US12350349B2 (en) 2016-08-03 2025-07-08 Washington University Gene editing of CAR-T cells for the treatment of T cell malignancies with chimeric antigen receptors
WO2025147545A1 (en) 2024-01-03 2025-07-10 Juno Therapeutics, Inc. Lipid nanoparticles for delivery of nucleic acids and related methods and uses
WO2025151838A1 (en) 2024-01-12 2025-07-17 Sana Biotechnology, Inc. Safety switches to control in vitro and in vivo proliferation of cell therapy products
WO2025163107A1 (en) 2024-02-01 2025-08-07 Institut Gustave Roussy Immune cells defective for znf217 and uses thereof
WO2025176853A1 (en) 2024-02-22 2025-08-28 Miltenyi Biotec B.V. & Co. KG Cd4- or cd8-targeted retroviral vector particles for generation of cells expressing a bispecific chimeric antigen receptor
WO2025184421A1 (en) 2024-02-28 2025-09-04 Juno Therapeutics, Inc. Chimeric antigen receptors and antibodies specific for delta-like ligand 3 (dll3) and related methods
US12448432B2 (en) 2020-03-17 2025-10-21 AbelZeta Inc. Combined chimeric antigen receptor targeting CD19 and CD20 and application thereof
WO2025231185A1 (en) 2024-05-01 2025-11-06 Legend Biotech Ireland Limited Viral glycoprotein variants and uses thereof
WO2025235851A1 (en) 2024-05-10 2025-11-13 Juno Therapeutics, Inc. Genetically engineered t cells expressing a cd19 chimeric antigen receptor (car) and uses thereof for allogeneic cell therapy
WO2025250011A1 (en) 2024-05-29 2025-12-04 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Treatment for cancer
US12491153B2 (en) 2018-01-03 2025-12-09 Qu Biologics Inc. Innate targeting of adoptive cellular therapies
WO2025259108A1 (en) 2024-06-11 2025-12-18 Prinses Máxima Centrum Voor Kinderoncologie B.V. Brain organoid
WO2026020055A2 (en) 2024-07-18 2026-01-22 Juno Therapeutics, Inc. Methods for assessing exosomes in a cell composition and related uses
WO2026025092A1 (en) 2024-07-26 2026-01-29 Juno Therapeutics, Inc. Synthetic promoters for t cell expression
EP4707385A2 (en) 2019-01-24 2026-03-11 Valorisation-HSJ, Limited Partnership Cell-specific transcriptional regulatory sequences and uses thereof
US12583903B2 (en) 2017-02-08 2026-03-24 AbelZeta Inc. Construction of chimeric antigen receptor targeting CD20 antigen and activity identification of engineered T cells thereof
WO2026062222A1 (en) 2024-09-20 2026-03-26 Institut Curie Novel protein isoforms and uses
US12590321B2 (en) 2016-03-19 2026-03-31 Exuma Biotech Corp. Methods and compositions for genetically modifying and expanding lymphocytes and regulating the activity thereof

Families Citing this family (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107164330A (zh) 2011-04-08 2017-09-15 贝勒医学院 使用嵌合细胞因子受体逆转肿瘤微环境的影响
KR20150029714A (ko) * 2012-07-13 2015-03-18 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 이중특이적 항체의 공-도입에 의한 ｃａｒ 세포의 활성 증강
WO2015120187A1 (en) 2014-02-05 2015-08-13 The University Of Chicago Chimeric antigen receptors recognizing cancer-spevific tn glycopeptide variants
GB201506423D0 (en) 2015-04-15 2015-05-27 Tc Biopharm Ltd Gamma delta T cells and uses thereof
AR102417A1 (es) * 2014-11-05 2017-03-01 Lilly Co Eli Anticuerpos biespecíficos anti-tnf- / anti-il-23
JP7264592B2 (ja) 2015-01-26 2023-04-25 ザ ユニバーシティー オブ シカゴ ＩＬ１３Ｒα２結合剤及び癌治療におけるその使用
WO2016123143A1 (en) 2015-01-26 2016-08-04 The University Of Chicago CAR T-CELLS RECOGNIZING CANCER-SPECIFIC IL 13Rα2
CN107530424A (zh) 2015-02-20 2018-01-02 俄亥俄州国家创新基金会 针对nkg2d和肿瘤相关抗原的二价抗体
JP7237449B2 (ja) * 2015-02-27 2023-03-13 アイセル・ジーン・セラピューティクス・エルエルシー 血液系腫瘍を標的としたキメラ抗体受容体（ＣＡＲｓ）の構成およびその使用方法
KR102133857B1 (ko) * 2015-03-02 2020-07-20 이노베이티브 셀룰러 테라퓨틱스 코퍼레이션 리미티드 Ｐｄ－ｌ１에 의해 유도된 면역관용의 감소
AU2016246457B2 (en) 2015-04-06 2020-10-15 Cytoimmune Therapeutics, Inc. EGFR-directed car therapy for glioblastoma
GB201507368D0 (en) 2015-04-30 2015-06-17 Ucl Business Plc Cell
CN107995913B (zh) 2015-05-18 2022-02-11 T细胞受体治疗公司 使用融合蛋白对tcr重编程的组合物和方法
CA2986755A1 (en) 2015-05-28 2016-12-01 Armo Biosciences, Inc. Pegylated interleukin-10 for use in treating cancer
US11173179B2 (en) 2015-06-25 2021-11-16 Icell Gene Therapeutics Llc Chimeric antigen receptor (CAR) targeting multiple antigens, compositions and methods of use thereof
CN108243607A (zh) 2015-09-09 2018-07-03 西雅图儿童医院（Dba西雅图儿童研究所） 用于免疫疗法的巨噬细胞的遗传工程
ES2980794T3 (es) 2015-09-15 2024-10-03 Acerta Pharma Bv Combinaciones terapéuticas de un inhibidor de CD19 y un inhibidor de BTK
WO2017058752A1 (en) 2015-09-28 2017-04-06 Trustees Of Dartmouth College Chimeric antigen receptor anti-inflammatory cells and methods of use
PE20240096A1 (es) 2015-10-02 2024-01-18 Hoffmann La Roche Anticuerpos biespecificos especificos para un receptor de tnf coestimulador
EP3419618A4 (en) * 2016-02-26 2019-11-06 iCell Gene Therapeutics, LLC CHIMERIC ANTIGEN RECEPTORS (CAR) AGAINST HEMATOLOGIC MALIGNOMES, COMPOSITIONS AND METHODS OF USE THEREOF
IL261713B2 (en) * 2016-03-19 2023-09-01 F1 Oncology Inc Methods and preparations for the transfer of lymphocytes and their regulated expansion
US20190105348A1 (en) * 2016-04-08 2019-04-11 Unum Therapeutics Inc. Chimeric receptors and uses thereof in immune therapy
WO2017181101A1 (en) * 2016-04-15 2017-10-19 The Trustees Of The University Of Pennsylvania Compositions and methods of chimeric alloantigen receptor t cells
CN109312304A (zh) * 2016-04-20 2019-02-05 弗雷德哈钦森癌症研究中心 免疫调节性il2r融合蛋白及其用途
WO2017192536A1 (en) 2016-05-02 2017-11-09 University Of Kansas Eliminating mhc restriction from the t cell receptor as a strategy for immunotherapy
SG11201810640RA (en) 2016-06-08 2018-12-28 Intrexon Corp Cd33 specific chimeric antigen receptors
JP7114490B2 (ja) 2016-06-24 2022-08-08 アイセル・ジーン・セラピューティクス・エルエルシー キメラ抗体受容体（ＣＡＲｓ）の構成およびその使用方法
EP3472318B1 (en) * 2016-07-08 2023-09-06 Exuma Biotech Corp. Methods and compositions for transducing lymphocytes and regulating the activity thereof
EP3494138A1 (en) 2016-08-02 2019-06-12 TCR2 Therapeutics Inc. Compositions and methods for tcr reprogramming using fusion proteins
EP4282969A3 (en) * 2016-09-02 2024-01-31 Lentigen Technology, Inc. Compositions and methods for treating cancer with duocars
JP2020501512A (ja) * 2016-09-23 2020-01-23 ユニバーシティ オブ サザン カリフォルニア キメラ抗原受容体およびその組成物ならびにそれらの使用の方法
EP3519443A4 (en) * 2016-09-30 2020-06-10 Baylor College of Medicine CHIMERIC ANTIGEN RECEPTOR THERAPY WITH REDUCED CYTOTOXICITY FOR VIRAL DISEASE
CA3036745A1 (en) 2016-10-07 2018-04-12 TCR2 Therapeutics Inc. Compositions and methods for t-cell receptors reprogramming using fusion proteins
JP2020500031A (ja) * 2016-10-11 2020-01-09 ミネルバ バイオテクノロジーズ コーポレーション ヒト化抗ｍｕｃ１＊抗体及び開裂酵素の使用
US11851491B2 (en) 2016-11-22 2023-12-26 TCR2 Therapeutics Inc. Compositions and methods for TCR reprogramming using fusion proteins
CN110291200B (zh) 2016-12-12 2024-05-14 西雅图儿童医院（Dba西雅图儿童研究所） 对哺乳动物细胞中转基因表达的药剂配体诱导具有增大的灵敏度的嵌合转录因子变异体
US20180100016A1 (en) * 2016-12-22 2018-04-12 Xiaotong Song Use of car-modified human natural killer cells to treat cancer
AR110424A1 (es) 2016-12-23 2019-03-27 Macrogenics Inc Moléculas de unión a adam9 y métodos de uso de las mismas
WO2018132506A1 (en) 2017-01-10 2018-07-19 The General Hospital Corporation Chimeric antigen receptors based on alternative signal 1 domains
CN110612119B (zh) 2017-02-07 2024-10-29 西雅图儿童医院（Dba西雅图儿童研究所） 磷脂醚(ple)car t细胞肿瘤靶向(ctct)剂
AU2018236450A1 (en) 2017-03-16 2019-10-03 The General Hospital Corporation Chimeric antigen receptors targeting CD37
WO2018195339A1 (en) 2017-04-19 2018-10-25 Board Of Regents, The University Of Texas System Immune cells expressing engineered antigen receptors
WO2018237325A1 (en) * 2017-06-22 2018-12-27 University Of Southern California Combination cancer therapy using chimeric antigen receptor engineered natural killer cells as chemotherapeutic drug carriers
WO2019018402A2 (en) * 2017-07-17 2019-01-24 Janssen Biotech, Inc. ANTIGEN-BINDING REGIONS DIRECTED AGAINST FIBRONECTIN TYPE III DOMAINS AND METHODS OF USING THE SAME
CN109423495A (zh) * 2017-08-24 2019-03-05 上海恒润达生生物科技有限公司 一种双靶向嵌合抗原受体及其用途
US20200268795A1 (en) * 2017-09-22 2020-08-27 The Regents Of The University Of California Interferon-gamma attenuates anti-tumor immune response to checkpoint blockade
EP3714041A1 (en) 2017-11-22 2020-09-30 Iovance Biotherapeutics, Inc. Expansion of peripheral blood lymphocytes (pbls) from peripheral blood
MA51428A (fr) * 2017-12-22 2020-11-04 Bluebird Bio Inc Récepteur d'antigène chimérique multivalent
CA3083779A1 (en) 2017-12-22 2019-06-27 Fate Therapeutics, Inc. Enhanced immune effector cells and use thereof
JP2021508468A (ja) * 2017-12-29 2021-03-11 シティ・オブ・ホープＣｉｔｙ ｏｆ Ｈｏｐｅ メディトープ対応ｔ細胞
US10561686B2 (en) 2018-01-12 2020-02-18 Innovative Cellular Therapeutics CO., LTD. Modified cell expansion and uses thereof
SG11202007426XA (en) 2018-02-06 2020-09-29 Seattle Childrens Hospital Dba Seattle Childrens Res Inst Fluorescein-specific cars exhibiting optimal t cell function against fl-ple labelled tumors
CN111886028A (zh) 2018-02-09 2020-11-03 达特茅斯大学理事会 用于治疗神经退行性疾病和障碍的嵌合抗原受体
JP7273421B2 (ja) 2018-02-21 2023-05-15 ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム ナチュラルキラー細胞の活性化および拡大のための方法ならびにその使用
SG11202008926RA (en) 2018-03-14 2020-10-29 Seattle Childrens Hospital Dba Seattle Childrens Res Inst Il-13 receptor alpha 2 targeted, zetakine directed t cell immunotherapy
JP7575271B2 (ja) 2018-03-29 2024-10-29 フェイト セラピューティクス，インコーポレイテッド 操作された免疫エフェクター細胞およびその使用
CN108715616A (zh) * 2018-04-27 2018-10-30 上海恒润达生生物科技有限公司 靶向人源化间皮素的嵌合抗原受体方法和用途
US20210230289A1 (en) 2018-06-12 2021-07-29 The Regents Of The University Of California Single-chain bispecific chimeric antigen receptors for the treatment of cancer
CN112533629A (zh) 2018-06-19 2021-03-19 阿尔莫生物科技股份有限公司 结合使用il-10药剂与嵌合抗原受体细胞疗法的组合物和方法
CN110615842B (zh) * 2018-06-20 2023-05-09 上海隆耀生物科技有限公司 一种包含共刺激受体的嵌合抗原受体及应用
WO2019246546A1 (en) * 2018-06-22 2019-12-26 The General Hospital Corporation Chimeric antigen receptors targeting cd37 and cd19
WO2020037120A1 (en) * 2018-08-16 2020-02-20 Nantbio, Inc. Il7-il15 txm compositions and methods
WO2020061796A1 (en) * 2018-09-26 2020-04-02 Hrain Biotechnology Co., Ltd. Bcma-and-cd19-targeting chimeric antigen receptor and uses thereof
EP3632460A1 (en) 2018-10-05 2020-04-08 St. Anna Kinderkrebsforschung A group of chimeric antigen receptors (cars)
CA3112310C (en) 2018-10-05 2025-05-06 Universitat Fur Bodenkultur Wien CHIMERIC ANTIGEN RECEPTOR GROUP (CAR)
US12600776B2 (en) 2018-10-19 2026-04-14 Cartexell Inc. Anti-L1CAM antibody or antigen-binding fragment thereof and chimeric antigen receptor comprising same
WO2020092057A1 (en) 2018-10-30 2020-05-07 Yale University Compositions and methods for rapid and modular generation of chimeric antigen receptor t cells
SG11202104524YA (en) 2018-11-01 2021-05-28 Gracell Biotechnologies Shanghai Co Ltd Compositions and methods for t cell engineering
US12466892B2 (en) 2018-11-08 2025-11-11 The Regents Of The University Of California Systems and methods for targeting cancer cells
US10918667B2 (en) 2018-11-20 2021-02-16 Innovative Cellular Therapeutics CO., LTD. Modified cell expressing therapeutic agent and uses thereof
US12590148B2 (en) 2018-11-26 2026-03-31 Nkarta, Inc. Methods for the simultaneous expansion of multiple immune cell types, related compositions and uses of same in cancer immunotherapy
KR102943217B1 (ko) 2018-12-02 2026-03-25 페이트 세러퓨틱스, 인코포레이티드 향상된 iPSC 유래 효과기 세포를 사용한 면역요법
MA54540A (fr) * 2018-12-19 2021-10-27 Regeneron Pharma Anticorps anti-cd28 x anti-cd22 bispécifiques et leurs utilisations
EP3908613A4 (en) * 2019-01-07 2022-10-19 Celluris Participações Ltda. BISPECIFIC IN-TANDEM RECEPTOR CAR AND METHODS FOR MODULATION OF THE TUMOR MICROAREA
CN111544585B (zh) * 2019-02-11 2024-12-27 北京卡替医疗技术有限公司 一种可助推免疫细胞在体内扩增的佐剂
US20230348556A1 (en) * 2019-02-21 2023-11-02 Arbele Limited Artificial immunosurveillance chimeric antigen receptor and cells expressing the same
US20220133795A1 (en) 2019-03-01 2022-05-05 Iovance Biotherapeutics, Inc. Expansion of Tumor Infiltrating Lymphocytes From Liquid Tumors and Therapeutic Uses Thereof
AU2020232691B2 (en) 2019-03-05 2023-06-29 Nkarta, Inc. CD19-directed chimeric antigen receptors and uses thereof in immunotherapy
ES2911273T3 (es) * 2019-03-19 2022-05-18 Miltenyi Biotec Bv & Co Kg Método para proporcionar células personalizadas con receptores de antígeno quimérico (CAR)
CN120172958A (zh) 2019-04-12 2025-06-20 C4医药公司 Ikaros和aiolos的三环降解物
EP3962527A4 (en) 2019-04-30 2023-11-01 Senti Biosciences, Inc. CHIMERIC RECEPTORS AND METHODS OF USE THEREOF
CA3139319A1 (en) * 2019-05-07 2020-11-12 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of polypeptides and chimeric antigen receptors via hinge domains
CA3139346A1 (en) 2019-05-07 2020-11-12 Gracell Biotechnologies (Shanghai) Co., Ltd. Engineered immune cell targeting bcma and use thereof
BR112022000641A2 (pt) 2019-07-17 2022-03-29 Fate Therapeutics Inc Modificação genética de célula efetora imune e uso da mesma
CN112390891B (zh) * 2019-08-14 2022-06-03 苏州方德门达新药开发有限公司 嵌合抗原受体及其构建方法和应用
JP7831937B2 (ja) 2019-09-03 2026-03-17 クリエイト・メディシンズ，インコーポレーテッド ゲノム組込みのための方法および組成物
US20240082403A1 (en) * 2019-10-11 2024-03-14 The Regents Of The University Of California Chimeric Antigen Receptors against Human Cytomegalovirus
AU2021211713A1 (en) 2020-01-23 2022-08-25 The Children's Medical Center Corporation Stroma-free T cell differentiation from human pluripotent stem cells
AU2021217003A1 (en) 2020-02-04 2022-09-15 Seattle Children's Hospital (dba Seattle Children's Research Institute) Anti-dinitrophenol chimeric antigen receptors
EP4081552A4 (en) * 2020-02-17 2024-01-24 University of Virginia Patent Foundation Car t cells targeting the integrin alphav beta3 exhibit robust anti-tumor responses against gliomas and other solid tumor malignancies
WO2021202799A2 (en) 2020-03-31 2021-10-07 Fred Hutchinson Cancer Research Center Chimeric antigen receptors targeting cd33
US20210340524A1 (en) 2020-05-01 2021-11-04 Massachusetts Institute Of Technology Methods for identifying chimeric antigen receptor-targeting ligands and uses thereof
US20230348854A1 (en) * 2020-05-08 2023-11-02 Seattle Children's Hospital D/B/A Seattle Children's Research Institute Chimeric antigen receptors (cars) targeting natural killer cells
US20230203168A1 (en) * 2020-06-02 2023-06-29 H. Lee Moffitt Cancer Center And Research Institute, Inc. Dual EGFR-MUC1 Chimeric Antigen Receptor T Cells
AU2021292695A1 (en) 2020-06-19 2023-02-02 Fate Therapeutics, Inc. Combining iPSC-derived effector cell types for immunotherapy use
JP2023538303A (ja) 2020-08-13 2023-09-07 イェール ユニバーシティー 所望の表現型を有するｃａｒ ｔ細胞の操作および選択のための組成物および方法
CA3193009A1 (en) * 2020-08-26 2022-03-03 The Regents Of The University Of California Methods and compositions for treating glioblastoma
US11661459B2 (en) 2020-12-03 2023-05-30 Century Therapeutics, Inc. Artificial cell death polypeptide for chimeric antigen receptor and uses thereof
AU2021392032A1 (en) 2020-12-03 2023-06-22 Century Therapeutics, Inc. Genetically engineered cells and uses thereof
CA3207861A1 (en) * 2021-02-11 2022-08-18 Carl H. June Ccr4-targeting chimeric antigen receptor cell therapy
CN115109754B (zh) * 2021-03-23 2025-04-01 复星凯瑞(上海)生物科技有限公司 抗EGFR和cMet双特异性嵌合抗原受体及其应用
CN113735978B (zh) * 2021-04-22 2023-06-30 河北森朗生物科技有限公司 靶向cd19的嵌合抗原受体、制备方法及其应用
AU2022272235A1 (en) 2021-05-11 2023-12-21 Create Medicines, Inc. Methods and compositions for genomic integration
CN118056012B (zh) * 2021-08-24 2025-05-30 赛斯尔擎生物技术（上海）有限公司 一种修饰细胞的方法
US20250009879A1 (en) * 2021-11-22 2025-01-09 The Asan Foundation Natural killer cell-specific chimeric antigen receptor and use thereof
US20250135002A1 (en) * 2022-02-04 2025-05-01 Duke University Compositions for and method of effecting tumor cell death
WO2023173137A1 (en) 2022-03-11 2023-09-14 Yale University Compositions and methods for efficient and stable genetic modification of eukaryotic cells
CA3247010A1 (en) 2022-04-08 2023-10-12 Ono Pharmaceutical Co., Ltd. CHIMERIC ANTIGEN RECEPTOR FOR TUMOR TARGETING
EP4504914A4 (en) 2022-04-08 2026-04-29 Fate Therapeutics Inc Cells having solid tumor targeting backbone and use thereof
CN117305248A (zh) * 2022-09-09 2023-12-29 复星凯特生物科技有限公司 抗EGFR和cMet双特异性嵌合抗原受体及其应用
WO2024098024A1 (en) 2022-11-04 2024-05-10 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof
EP4676499A2 (en) * 2023-03-10 2026-01-14 The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone Methods and compositions for cellular immunotherapy- fib4
EP4676945A2 (en) * 2023-03-10 2026-01-14 The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone Methods and compositions for cellular immunotherapy - fib2
WO2024192134A1 (en) * 2023-03-13 2024-09-19 Immpact Bio Usa, Inc. Bispecific cars for the treatment of lupus and autoimmune diseases
WO2024226829A2 (en) 2023-04-26 2024-10-31 Yale University Enpp3-binding molecules, compositions formed therefrom, and methods of use thereof for the treatment of cancer
WO2025059162A1 (en) 2023-09-11 2025-03-20 Dana-Farber Cancer Institute, Inc. Car-engager containing il-2 variants to enhance the functionality of car t cells

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5741899A (en) * 1995-02-02 1998-04-21 Cell Genesys, Inc. Chimeric receptors comprising janus kinase for regulating cellular pro liferation
US20030077249A1 (en) * 1995-12-21 2003-04-24 Christopher Robert Bebbington Cell activation process and reagents therefor
US20050113564A1 (en) * 2003-11-05 2005-05-26 St. Jude Children's Research Hospital Chimeric receptors with 4-1BB stimulatory signaling domain
US20100135974A1 (en) * 2007-01-31 2010-06-03 Yeda Research And Development Co. Ltd. Redirected, genetically-engineered t regulatory cells and their use in suppression of autoimmune and inflammatory disease
US20100189690A1 (en) * 2006-09-27 2010-07-29 Bundesrepublik Deutschland, Letztvertreten Durch D En Prasidenten Des Paul-Ehrich-Instituts Pseudotyping of retroviral vectors, methods for production and use thereof for targeted gene transfer and high throughput screening
US20100323420A1 (en) * 1993-02-12 2010-12-23 Gerald Crabtree Regulated apoptosis
US20110044986A1 (en) * 2007-12-21 2011-02-24 Amgen Inc. Anti-amyloid antibodies and uses thereof
WO2011056894A2 (en) * 2009-11-03 2011-05-12 Jensen Michael C TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (EGFRt) FOR TRANSDUCED T CELL SELECTION
US20110135657A1 (en) * 2009-12-07 2011-06-09 Amgen Inc. Human antigen binding proteins that bind beta-klotho, fgf receptors and complexes thereof
US20110223129A1 (en) * 2001-04-30 2011-09-15 City Of Hope Chimeric immunoreceptor useful in treating human cancers

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6103521A (en) 1995-02-06 2000-08-15 Cell Genesys, Inc. Multispecific chimeric receptors
JP3850528B2 (ja) 1997-09-30 2006-11-29 株式会社リコー シート材給送装置
KR101456728B1 (ko) * 2006-09-08 2014-10-31 메디뮨 엘엘씨 인간화 항-ｃｄ19 항체, 및 이것의 종양학, 이식 및 자가면역 질환의 치료에서의 용도
EP2012122A1 (en) * 2007-07-06 2009-01-07 Medigene AG Mutated parvovirus structural proteins as vaccines
BRPI0910482A2 (pt) * 2008-04-29 2019-09-24 Abbott Lab imunoglobinas de domínio variável duplo e usos das mesmas
US8465743B2 (en) * 2009-10-01 2013-06-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Anti-vascular endothelial growth factor receptor-2 chimeric antigen receptors and use of same for the treatment of cancer
JP6850528B2 (ja) 2012-02-13 2021-03-31 シアトル チルドレンズ ホスピタル ドゥーイング ビジネス アズ シアトル チルドレンズ リサーチ インスティテュート 二重特異性キメラ抗原受容体およびその治療的使用
US20130280220A1 (en) * 2012-04-20 2013-10-24 Nabil Ahmed Chimeric antigen receptor for bispecific activation and targeting of t lymphocytes
JP2019055330A (ja) 2019-01-21 2019-04-11 株式会社三洋物産 遊技機

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100323420A1 (en) * 1993-02-12 2010-12-23 Gerald Crabtree Regulated apoptosis
US5741899A (en) * 1995-02-02 1998-04-21 Cell Genesys, Inc. Chimeric receptors comprising janus kinase for regulating cellular pro liferation
US20030077249A1 (en) * 1995-12-21 2003-04-24 Christopher Robert Bebbington Cell activation process and reagents therefor
US20110223129A1 (en) * 2001-04-30 2011-09-15 City Of Hope Chimeric immunoreceptor useful in treating human cancers
US20050113564A1 (en) * 2003-11-05 2005-05-26 St. Jude Children's Research Hospital Chimeric receptors with 4-1BB stimulatory signaling domain
US20100189690A1 (en) * 2006-09-27 2010-07-29 Bundesrepublik Deutschland, Letztvertreten Durch D En Prasidenten Des Paul-Ehrich-Instituts Pseudotyping of retroviral vectors, methods for production and use thereof for targeted gene transfer and high throughput screening
US20100135974A1 (en) * 2007-01-31 2010-06-03 Yeda Research And Development Co. Ltd. Redirected, genetically-engineered t regulatory cells and their use in suppression of autoimmune and inflammatory disease
US20110044986A1 (en) * 2007-12-21 2011-02-24 Amgen Inc. Anti-amyloid antibodies and uses thereof
WO2011056894A2 (en) * 2009-11-03 2011-05-12 Jensen Michael C TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (EGFRt) FOR TRANSDUCED T CELL SELECTION
US20110135657A1 (en) * 2009-12-07 2011-06-09 Amgen Inc. Human antigen binding proteins that bind beta-klotho, fgf receptors and complexes thereof

Non-Patent Citations (27)

* Cited by examiner, † Cited by third party
Title
"Animal Cell Culture", 1986
"Cell Biology: A Laboratory Handbook", vol. I-III, 1994
"Current Protocols in Immunology", vol. I-III, 1994
"Current Protocols in Molecular Biology", vol. I-III, 1994
"Current Prptocols in Immunology", 1991
"Immobilized Cells And Enzymes", 1986, IRL PRESS
"Nucleic Acid Hybridization", 1985
"Oligonucleotide Synthesis", 1984
"Practical Guide To Molecular Cloning B. Perbal", 1984
"Remington: The Science and Practice of Pharmacy", 2000, WILLIAMS & WILKINS
"Transcription And Translation", 1984
BEDZYK ET AL.: "Immunological and structural characterization of a high affinity anti-fluorescein single-chain antibody", J. BIOL. CHEM., vol. 265, 1990, pages 18615
BERGER ET AL.: "Adoptive transfer of virus-specific and tumor-specific T cell immunity", CURR OPIN IMMUNOL, vol. 21, no. 2, 2009, pages 224 - 232, XP026058400, DOI: doi:10.1016/j.coi.2009.02.010
CHAUDHARY ET AL.: "A recombinant single-chain immunotoxin composed of anti-Tac variable regions and a truncated diphtheria toxin", PROC. NATL. ACAD. SCI., vol. 87, 1990, pages 9491
GIBSON: "Enzymatic assembly of DNA molecules upto several hindred kilobases", NATURE METHODS, vol. 6, 2009, pages 343 - 345
KOWOLIK CK. ET AL.: "CD28 costimuation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells", CANCER RES., vol. 66, no. 22, 2006, pages 10995 - 11004, XP055044266, DOI: doi:10.1158/0008-5472.CAN-06-0160
KUFER, PETER; LUTTERBIISE, RALF; BAEUERLE, PATRICK A.: "A revival of bispecific antibodies", TRENDS IN BIOTECHNOLOGY, vol. 22, no. 5, 2004, pages 238 - 244, XP004504363, DOI: doi:10.1016/j.tibtech.2004.03.006
MARCH: "Advanced Organic Chemistry Reactions, Mechanisms and Structure", 2001, J. WILEY & SONS
MICHAEL JENSEN ET AL.: "CD20 is a molecular target for scFvFc:zeta receptor redirected T-cells: implications for cellular immunotherapy of CD20+ malignancy", BIOLOGY OF BLOOD AND MARROW TRANSPLANT, vol. 4, 1998, pages 75 - 83, XP000910525, DOI: doi:10.1053/bbmt.1998.v4.pm9763110
SAMBROOK ET AL.: "Molecular Cloning: A Laboratory Manual", 1989
SAMBROOK; RUSSEL: "Molecular Cloning: A Laboratory Manual", 2001, COLD SPRING HARBOR LABORATORY PRESS
SCHMITZ N; DREGER P; GLASS B; SUREDA A: "Allogeneic transplantation in lymphoma: current status", HAEMATOLOGICA, vol. 92, no. 11, 2007, pages 1533 - 1548
SEITARO TERAKURA ET AL.: "Generation of CD19-CAR modified CD8+ T-cells derived from virus-specific central memory T-cells", BLOOD, 26 October 2011 (2011-10-26)
SINGLETON ET AL.: "Dictionary of Microbiology and Molecular Biology", 2001, J. WILEY & SONS
SZYMCZAK AL. ET AL.: "Correction of multi-gene deficiency in vivo using a ''self-cleaving'' 2A peptide-based retroviral vector", NAT BIOTECHNOL, vol. 22, no. 5, 2004, pages 589 - 594, XP002369309, DOI: doi:10.1038/nbt957
WANG ET AL.: "A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells", BLOOD, vol. 118, no. 5, pages 1255 - 1263, XP055062819, DOI: doi:10.1182/blood-2011-02-337360
XIONG, CHENG-YI; NATARAJAN, A; SHI, XB; DENARDO, GL; DENARDO, SJ: "Development of tumor targeting anti-MUC-1 multimer: effects of di-scFv unpaired cysteine location on PEGylation and tumor binding", PROTEIN ENGINEERING DESIGN AND SELECTION, vol. 19, no. 8, 2006, pages 359 - 367, XP009147927, DOI: doi:10.1093/protein/gzl020

Cited By (841)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9447194B2 (en) 2012-02-13 2016-09-20 Seattle Children's Hospital Bispecific chimeric antigen receptors and encoding polynucleotides thereof
US10829556B2 (en) 2012-02-13 2020-11-10 Seattle Children's Hospital Polynucleotides encoding bispecific chimeric antigen receptors
US11639387B2 (en) 2012-02-13 2023-05-02 Seattle Children's Hospital Bispecific chimeric antigen receptors, encoding polynucleotides thereof and methods of use thereof to treat disease
US10189903B2 (en) 2012-02-13 2019-01-29 Seattle Children's Hospital Bispecific chimeric antigen receptors and methods of use thereof to treat cancer
US12091459B2 (en) 2012-02-13 2024-09-17 Seattle Children's Hospital Bispecific chimeric antigen receptors, encoding polynucleotides and use of receptors thereof to treat cancer
US12466885B2 (en) 2012-02-13 2025-11-11 Seattle Children's Hospital Bispecific chimeric antigen receptors and encoding polynucleotides, vectors and cells thereof
EP2817318A4 (en) * 2012-02-22 2016-04-27 Univ Pennsylvania COMPOSITIONS AND METHOD FOR GENERATING A PERSISTENT POPULATION OF T CELLS FOR CANCER TREATMENT
US12350334B2 (en) 2012-02-22 2025-07-08 The Trustees Of The University Of Pennsylvania Compositions and methods for generating a persisting population of T cells useful for the treatment of cancer
US10040846B2 (en) 2012-02-22 2018-08-07 The Trustees Of The University Of Pennsylvania Compositions and methods for generating a persisting population of T cells useful for the treatment of cancer
US11299536B2 (en) 2012-02-22 2022-04-12 The Trustees Of The University Of Pennsylvania Compositions and methods for generating a persisting population of T cells useful for the treatment of cancer
US10800840B2 (en) 2012-02-22 2020-10-13 The Trustees Of The University Of Pennsylvania Compositions and methods for generating a persisting population of T cells useful for the treatment of cancer
US11827889B2 (en) 2012-04-11 2023-11-28 The U.S.A., As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting B-cell maturation antigen
US20130280220A1 (en) * 2012-04-20 2013-10-24 Nabil Ahmed Chimeric antigen receptor for bispecific activation and targeting of t lymphocytes
US10780118B2 (en) 2012-08-20 2020-09-22 Fred Hutchinson Cancer Research Center Method and compositions for cellular immunotherapy
US10869889B2 (en) 2012-08-20 2020-12-22 Fred Hutchinson Cancer Research Center Method and compositions for cellular immunotherapy
US10736918B2 (en) 2012-08-20 2020-08-11 Fred Hutchinson Cancer Research Center Method and compositions for cellular immunotherapy
US11130820B2 (en) 2012-12-20 2021-09-28 Celgene Corporation Chimeric antigen receptors
US12150981B2 (en) 2012-12-20 2024-11-26 Purdue Research Foundation Chimeric antigen receptor-expressing T cells as anti-cancer therapeutics
US9394368B2 (en) 2013-02-20 2016-07-19 Novartis Ag Treatment of cancer using humanized anti-EGFRvIII chimeric antigen receptor
US12559562B2 (en) 2013-02-20 2026-02-24 Novartis Ag Treatment of cancer using humanized anti-EGFRvIII chimeric antigen receptor
US11865167B2 (en) 2013-02-20 2024-01-09 Novartis Ag Treatment of cancer using humanized anti-EGFRvIII chimeric antigen receptor
US10308717B2 (en) 2013-02-20 2019-06-04 Novartis Ag Treatment of cancer using humanized anti-EGFRvIII chimeric antigen receptor
US9662354B2 (en) 2013-03-14 2017-05-30 Elwha Llc Compositions, methods, and computer systems related to making and administering modified T cells
US9499855B2 (en) 2013-03-14 2016-11-22 Elwha Llc Compositions, methods, and computer systems related to making and administering modified T cells
US20140274801A1 (en) * 2013-03-14 2014-09-18 Elwha Llc Compositions, methods, and computer systems related to making and administering modified t cells
US9587237B2 (en) 2013-03-14 2017-03-07 Elwha Llc Compositions, methods, and computer systems related to making and administering modified T cells
US10967005B2 (en) 2013-03-15 2021-04-06 Celgene Corporation Modified T lymphocytes comprising a BAFF antibody-inducible caspase and methods of apoptosis
US11918606B2 (en) 2013-03-15 2024-03-05 City Of Hope CD123-specific chimeric antigen receptor redirected t cells and methods of their use
US11806365B2 (en) 2013-03-15 2023-11-07 Celgene Corporation Modified T lymphocytes comprising a CD52 antibody-inducible caspase and methods of apoptosis
US9657105B2 (en) 2013-03-15 2017-05-23 City Of Hope CD123-specific chimeric antigen receptor redirected T cells and methods of their use
US10660916B2 (en) 2013-03-15 2020-05-26 City Of Hope CD123-specific chimeric antigen receptor redirected T cells and methods of their use
US11845794B2 (en) 2013-05-03 2023-12-19 Ohio State Innovation Foundation CS1-specific chimeric antigen receptor engineered immune effector cells
EP3027755A4 (en) * 2013-08-02 2017-01-18 The Regents of The University of California Engineering antiviral t cell immunity through stem cells and chimeric antigen receptors
US9951118B2 (en) 2013-08-02 2018-04-24 The Regents Of The University Of California Engineering antiviral T cell immunity through stem cells and chimeric antigen receptors
US10391155B2 (en) 2013-10-15 2019-08-27 The Scripps Research Institute Peptidic chimeric antigen receptor T cell switches and uses thereof
CN105814083A (zh) * 2013-10-15 2016-07-27 加州生物医学研究所 嵌合抗原受体t细胞开关和其用途
WO2015057852A1 (en) * 2013-10-15 2015-04-23 The California Institute For Biomedical Research Chimeric antigen receptor t cell switches and uses thereof
US9624276B2 (en) 2013-10-15 2017-04-18 The California Institute For Biomedical Research Peptidic chimeric antigen receptor T cell switches and uses thereof
JP7046112B2 (ja) 2013-10-31 2022-04-01 フレッド ハッチンソン キャンサー リサーチ センター 改変された造血幹／前駆細胞及び非エフェクターｔ細胞、そしてそれらの用途
AU2019204429B2 (en) * 2013-10-31 2021-10-07 Fred Hutchinson Cancer Center Modified hematopoietic stem/progenitor and non-T effector cells, and uses thereof
WO2015066551A3 (en) * 2013-10-31 2015-06-25 Fred Hutchinson Cancer Research Center Modified hematopoietic stem/progenitor and non-t effector cells, and uses thereof
JP2017500009A (ja) * 2013-10-31 2017-01-05 フレッド ハッチンソン キャンサー リサーチ センター 改変された造血幹／前駆細胞及び非エフェクターｔ細胞、そしてそれらの用途
EP4083062A1 (en) * 2013-10-31 2022-11-02 Fred Hutchinson Cancer Center Modified hematopoietic stem/progenitor and non-t effector cells, and uses thereof
RU2733652C2 (ru) * 2013-10-31 2020-10-06 Фред Хатчинсон Кэнсер Рисерч Сентер МОДИФИЦИРОВАННЫЕ ГЕМОПОЭТИЧЕСКИЕ СТВОЛОВЫЕ КЛЕТКИ/КЛЕТКИ-ПРЕДШЕСТВЕННИКИ И Не-Т ЭФФЕКТОРНЫЕ КЛЕТКИ, И ИХ ПРИМЕНЕНИЕ
JP2020141671A (ja) * 2013-10-31 2020-09-10 フレッド ハッチンソン キャンサー リサーチ センター 改変された造血幹／前駆細胞及び非エフェクターｔ細胞、そしてそれらの用途
EP3858378A1 (en) * 2013-11-21 2021-08-04 Autolus Limited Cell
US10676528B2 (en) * 2013-12-06 2020-06-09 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Thymic stromal lymphopoietin receptor-specific chimeric antigen receptors and methods using same
US11834509B2 (en) 2013-12-06 2023-12-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Thymic stromal lymphopoietin receptor-specific chimeric antigen receptors and methods using same
US20160311910A1 (en) * 2013-12-06 2016-10-27 The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services Thymic stromal lymphopoietin receptor-specific chimeric antigen receptors and methods using same
US11993652B2 (en) 2013-12-20 2024-05-28 Fred Hutchinson Cancer Center Tagged chimeric effector molecules and receptors thereof
CN105980402A (zh) * 2013-12-20 2016-09-28 弗雷德哈钦森癌症研究中心 带标签的嵌合效应分子及其受体
US10239948B2 (en) 2013-12-20 2019-03-26 Cellectis Method of engineering multi-input signal sensitive T cell for immunotherapy
CN113354744A (zh) * 2013-12-20 2021-09-07 弗雷德哈钦森癌症研究中心 带标签的嵌合效应分子及其受体
US10494434B2 (en) 2013-12-20 2019-12-03 Fred Hutchinson Cancer Research Center Tagged chimeric effector molecules and receptors thereof
WO2015092024A3 (en) * 2013-12-20 2015-08-13 Cellectis Method of engineering multi-input signal sensitive t cell for immunotherapy
EP3808410A1 (en) 2013-12-20 2021-04-21 Cellectis Method of engineering multi-input signal sensitive t cell for immunotherapy
WO2015095895A1 (en) * 2013-12-20 2015-06-25 Fred Hutchinson Cancer Research Center Tagged chimeric effector molecules and receptors thereof
CN105980402B (zh) * 2013-12-20 2021-06-15 弗雷德哈钦森癌症研究中心 带标签的嵌合效应分子及其受体
RU2729463C2 (ru) * 2013-12-20 2020-08-06 Фред Хатчинсон Кансэр Рисёч Сентер Меченые химерные эффекторные молекулы и их рецепторы
US11046766B2 (en) 2013-12-20 2021-06-29 Fred Hutchinson Cancer Research Center Tagged chimeric effector molecules and receptors thereof
WO2015105522A1 (en) * 2014-01-13 2015-07-16 Forman Stephen J Chimeric antigen receptors (cars) having mutations in the fc spacer region and methods for their use
US12522667B2 (en) 2014-01-13 2026-01-13 City Of Hope Chimeric antigen receptors (CARs) having mutations in the fc spacer region and methods for their use
JP2021000095A (ja) * 2014-02-07 2021-01-07 マクマスター ユニバーシティー 三官能性ｔ細胞−抗原カプラ及び方法並びにこれらの使用
US11001621B1 (en) 2014-02-07 2021-05-11 Mcmaster University Trifunctional T cell-antigen coupler and methods and uses thereof
JP7179041B2 (ja) 2014-02-07 2022-11-28 マクマスター ユニバーシティー 三官能性ｔ細胞－抗原カプラ及び方法並びにこれらの使用
US11008376B2 (en) 2014-02-07 2021-05-18 Mcmaster University Trifunctional T cell-antigen coupler and methods and uses thereof
US11421014B2 (en) 2014-02-07 2022-08-23 Mcmaster University Trifunctional T cell-antigen coupler and methods and uses thereof
CN106459990B (zh) * 2014-02-07 2021-06-01 麦克马斯特大学 三功能t细胞抗原偶联物及其制备方法和用途
JP2017512054A (ja) * 2014-02-07 2017-05-18 マクマスター ユニバーシティー 三官能性ｔ細胞−抗原カプラ及び方法並びにこれらの使用
CN106459990A (zh) * 2014-02-07 2017-02-22 麦克马斯特大学 三功能t细胞抗原偶联物及其制备方法和用途
US10435453B2 (en) * 2014-02-07 2019-10-08 Mcmaster University Trifunctional T cell-antigen coupler and methods and uses thereof
US10196608B2 (en) * 2014-02-21 2019-02-05 Cellectis Method for in situ inhibition of regulatory T cells
US20170067022A1 (en) * 2014-02-21 2017-03-09 Cellectis Method for in situ inhibition of regulatory t cells
US20180208896A1 (en) * 2014-02-21 2018-07-26 Cellectis Method for in situ inhibition of regulatory t cells
WO2015142675A2 (en) 2014-03-15 2015-09-24 Novartis Ag Treatment of cancer using chimeric antigen receptor
US11919961B2 (en) 2014-03-19 2024-03-05 Cellectis CD123 specific chimeric antigen receptors for cancer immunotherapy
JP2020156482A (ja) * 2014-03-19 2020-10-01 セレクティスＣｅｌｌｅｃｔｉｓ 癌免疫治療のためのｃｄ１２３特異的キメラ抗原受容体
US10988541B2 (en) 2014-03-19 2021-04-27 Cellectis CD123 specific chimeric antigen receptors for cancer immunotherapy
CN104974261A (zh) * 2014-04-01 2015-10-14 上海中信国健药业股份有限公司 重组抗her2/ps双特异性抗体、其制备方法和应用
CN104974261B (zh) * 2014-04-01 2019-06-14 三生国健药业（上海）股份有限公司 重组抗her2/ps双特异性抗体、其制备方法和应用
EP3126390B1 (en) 2014-04-03 2019-10-16 Cellectis Cd33 specific chimeric antigen receptors for cancer immunotherapy
EP3126390B2 (en) † 2014-04-03 2026-01-07 Cellectis Cd33 specific chimeric antigen receptors for cancer immunotherapy
JP2017515460A (ja) * 2014-04-03 2017-06-15 セレクティスＣｅｌｌｅｃｔｉｓ 癌免疫療法のためのｃｄ３３特異的キメラ抗原受容体
US11414486B2 (en) 2014-04-10 2022-08-16 Seattle Children's Hospital Transgene genetic tags and methods of use
US12448445B2 (en) 2014-04-10 2025-10-21 Seattle Children's Hospital Transgene genetic tags and methods of use
CN106574246A (zh) * 2014-04-10 2017-04-19 西雅图儿童医院（Dba西雅图儿童研究所） 用于细胞免疫治疗的方法和组合物
US12258397B2 (en) 2014-04-10 2025-03-25 Seattle Children's Hospital Production of engineered T-cells by sleeping beauty transposon coupled with methotrexate selection
WO2015157391A1 (en) * 2014-04-10 2015-10-15 Seattle Children's Hospital (dba Seattle Children's Research Institute) Method and compositions for cellular immunotherapy
US11155616B2 (en) 2014-04-10 2021-10-26 Seattle Children's Hospital Drug regulated transgene expression
EP3129480A4 (en) * 2014-04-10 2017-08-16 Seattle Children's Hospital (DBA Seattle Children's Research Institute) Production of engineered t-cells by sleeping beauty transposon coupled with methotrexate selection
US10266592B2 (en) 2014-04-10 2019-04-23 Seattle Children's Hospital Drug regulated transgene expression
US10865242B2 (en) 2014-04-10 2020-12-15 Seattle Children's Hospital Method and compositions for cellular immunotherapy
JP2017513520A (ja) * 2014-04-10 2017-06-01 シアトル チルドレンズ ホスピタル， ディービーエー シアトル チルドレンズ リサーチ インスティテュート メトトレキサートによる選択と組み合わせたＳｌｅｅｐｉｎｇ Ｂｅａｕｔｙトランスポゾンによる遺伝子改変Ｔ細胞の製造
CN106661570B (zh) * 2014-04-10 2020-02-07 西雅图儿童医院（Dba西雅图儿童研究所） 通过与氨甲蝶呤选择偶联的睡美人转座子制备工程化t细胞
US12503507B2 (en) 2014-04-10 2025-12-23 Seattle Children's Hospital Defined composition gene modified T-cell products
US12202897B2 (en) 2014-04-10 2025-01-21 Seattle Children's Hospital Drug regulated transgene expression
AU2015243922B2 (en) * 2014-04-10 2021-08-05 Seattle Children's Hospital (dba Seattle Children's Research Institute) Production of engineered T-cells by sleeping beauty transposon coupled with methotrexate selection
US10611837B2 (en) 2014-04-10 2020-04-07 Seattle Children's Hospital Transgene genetic tags and methods of use
CN106661570A (zh) * 2014-04-10 2017-05-10 西雅图儿童医院（Dba西雅图儿童研究所） 通过与氨甲蝶呤选择偶联的睡美人转座子制备工程化t细胞
RU2751921C2 (ru) * 2014-04-10 2021-07-20 Сиэтл Чилдрен'С Хоспитал (Дба Сиэтл Чилдрен'С Ресёрч Инститьют) Продукты определенного состава, содержащие генетически модифицированные т-клетки
JP7503035B2 (ja) 2014-04-23 2024-06-19 ジュノー セラピューティクス インコーポレイテッド 養子療法用の免疫細胞集団を単離、培養、および遺伝子操作するための方法
JP2021180686A (ja) * 2014-04-23 2021-11-25 ジュノー セラピューティクス インコーポレイテッド 養子療法用の免疫細胞集団を単離、培養、および遺伝子操作するための方法
JP2024071445A (ja) * 2014-04-23 2024-05-24 ジュノー セラピューティクス インコーポレイテッド 養子療法用の免疫細胞集団を単離、培養、および遺伝子操作するための方法
US12296010B2 (en) 2014-04-23 2025-05-13 Juno Therapeutics, Inc. Methods for isolating, culturing, and genetically engineering immune cell populations for adoptive therapy
US12208137B2 (en) 2014-04-23 2025-01-28 Juno Therapeutics, Inc. Methods for isolating, culturing, and genetically engineering immune cell populations for adoptive therapy
JP2022093564A (ja) * 2014-04-23 2022-06-23 ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム キメラ抗原受容体（ｃａｒ）並びにその製造及び使用方法
JP7675243B2 (ja) 2014-04-23 2025-05-12 ジュノー セラピューティクス インコーポレイテッド 養子療法用の免疫細胞集団を単離、培養、および遺伝子操作するための方法
US9975960B2 (en) 2014-05-09 2018-05-22 Samsung Electronics Co., Ltd. Anti-HER2 antibody and anti-c-Met/anti-HER2 bispecific antibodies comprising the same
US10604740B2 (en) 2014-05-14 2020-03-31 Carsgen Therapeutics Limited Nucleic acids encoding chimeric antigen receptor proteins which bind epidermal growth factor receptor and T lymphocyte expressing the protein
JP2017515504A (ja) * 2014-05-14 2017-06-15 カースゲン セラピューティクス リミテッドＣａｒｓｇｅｎ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ キメラ抗原受容体タンパク質をコードする核酸およびキメラ抗原受容体タンパク質を発現するｔリンパ球
US11041021B2 (en) 2014-05-23 2021-06-22 University Of Florida Research Foundation, Incorporated Car based immunotherapy
WO2015179801A1 (en) * 2014-05-23 2015-11-26 University Of Florida Research Foundation, Inc. Car based immunotherapy
CN106535925A (zh) * 2014-05-23 2017-03-22 佛罗里达大学研究基金会有限公司 基于car的免疫治疗
US12371489B2 (en) 2014-05-23 2025-07-29 University Of Florida Research Foundation, Incorporated Car based immunotherapy
JP2021042224A (ja) * 2014-06-02 2021-03-18 アメリカ合衆国 Ｃｄ−１９を標的とするキメラ抗原受容体
JP2017522862A (ja) * 2014-06-02 2017-08-17 アメリカ合衆国 Ｃｄ−１９を標的とするキメラ抗原受容体
JP7799744B2 (ja) 2014-06-02 2026-01-15 アメリカ合衆国 Ｃｄ－１９を標的とするキメラ抗原受容体
JP7485650B2 (ja) 2014-06-02 2024-05-16 アメリカ合衆国 Ｃｄ－１９を標的とするキメラ抗原受容体
JP7004470B2 (ja) 2014-06-02 2022-02-10 アメリカ合衆国 Ｃｄ－１９を標的とするキメラ抗原受容体
AU2015270912B9 (en) * 2014-06-02 2021-01-21 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting CD-19
AU2020267211B2 (en) * 2014-06-02 2024-05-02 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting CD-19
KR20170013941A (ko) * 2014-06-02 2017-02-07 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 Cd-19를 표적화하는 키메라 항원 수용체
JP2022061988A (ja) * 2014-06-02 2022-04-19 アメリカ合衆国 Ｃｄ－１９を標的とするキメラ抗原受容体
AU2015270912B2 (en) * 2014-06-02 2020-09-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting CD-19
KR102668549B1 (ko) * 2014-06-02 2024-05-22 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 Cd19를 표적화하는 키메라 항원 수용체
JP2024105415A (ja) * 2014-06-02 2024-08-06 アメリカ合衆国 Ｃｄ－１９を標的とするキメラ抗原受容体
US11236161B2 (en) 2014-06-02 2022-02-01 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting CD-19
US12473359B2 (en) 2014-06-02 2025-11-18 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting CD-19
US10738278B2 (en) 2014-07-15 2020-08-11 Juno Therapeutics, Inc. Engineered cells for adoptive cell therapy
EP3169703B1 (en) 2014-07-16 2020-09-02 Hinrich Abken Chimeric antigen receptor and its use
US11084880B2 (en) 2014-07-21 2021-08-10 Novartis Ag Anti-BCMA chimeric antigen receptor
US12214037B2 (en) 2014-07-21 2025-02-04 Novartis Ag Treatment of cancer using humanized anti-BCMA chimeric antigen receptor
US10851166B2 (en) 2014-07-21 2020-12-01 Novartis Ag Treatment of cancer using a CD33 chimeric antigen receptor
US10568947B2 (en) 2014-07-21 2020-02-25 Novartis Ag Treatment of cancer using a CLL-1 chimeric antigen receptor
WO2016014530A1 (en) 2014-07-21 2016-01-28 Novartis Ag Combinations of low, immune enhancing. doses of mtor inhibitors and cars
US10174095B2 (en) 2014-07-21 2019-01-08 Novartis Ag Nucleic acid encoding a humanized anti-BCMA chimeric antigen receptor
US12338287B2 (en) 2014-07-21 2025-06-24 Novartis Ag Treatment of cancer using a CD33 chimeric antigen receptor
US9777061B2 (en) 2014-07-21 2017-10-03 Novartis Ag Treatment of cancer using a CD33 chimeric antigen receptor
US10752684B2 (en) 2014-07-29 2020-08-25 Cellectis ROR1 (NTRKR1) specific chimeric antigen receptors for cancer immunotherapy
US10544201B2 (en) 2014-07-31 2020-01-28 Cellectis ROR1 specific multi-chain chimeric antigen receptor
WO2016016343A1 (en) * 2014-07-31 2016-02-04 Cellectis Ror1 specific multi-chain chimeric antigen receptor
WO2016025454A3 (en) * 2014-08-12 2016-04-07 Anthrogenesis Corporation Car-t lymphocytes engineered to home to lymph node b cell zone, skin, or gastrointestinal tract
KR20170042325A (ko) * 2014-08-28 2017-04-18 바이오아트라, 엘엘씨 변형된 t 세포에 대한 조건부 활성 키메라 항원 수용체
JP2017532014A (ja) * 2014-08-28 2017-11-02 バイオアトラ、エルエルシー 修飾ｔ細胞に対する条件的活性型キメラ抗原受容体
US10533055B2 (en) 2014-08-28 2020-01-14 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for CD19
JP7286267B2 (ja) 2014-08-28 2023-06-05 バイオアトラ インコーポレイテッド 修飾ｔ細胞に対する条件的活性型キメラ抗原受容体
US11111288B2 (en) 2014-08-28 2021-09-07 Bioatla, Inc. Conditionally active chimeric antigen receptors for modified t-cells
KR20230172625A (ko) * 2014-08-28 2023-12-22 바이오아트라, 인코퍼레이티드 변형된 t 세포에 대한 조건부 활성 키메라 항원 수용체
WO2016033570A1 (en) 2014-08-28 2016-03-03 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for cd19
US11584927B2 (en) 2014-08-28 2023-02-21 Bioatla, Inc. Conditionally active chimeric antigen receptors for modified T-cells
KR102818922B1 (ko) * 2014-08-28 2025-06-11 바이오아트라, 인코퍼레이티드 변형된 t 세포에 대한 조건부 활성 키메라 항원 수용체
US11827714B2 (en) 2014-08-28 2023-11-28 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for CD19
EP3805267A1 (en) 2014-08-28 2021-04-14 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for cd19
KR102615681B1 (ko) * 2014-08-28 2023-12-18 바이오아트라, 인코퍼레이티드 변형된 t 세포에 대한 조건부 활성 키메라 항원 수용체
JP2017532019A (ja) * 2014-09-03 2017-11-02 バイオアトラ、エルエルシー 同じ真核細胞産生宿主における条件的活性型生物学的タンパク質の発見及び作製
US11987639B2 (en) 2014-09-04 2024-05-21 Cellectis Trophoblast glycoprotein (5T4, TPBG) specific chimeric antigen receptors for cancer immunotherapy
EP3189073B1 (en) 2014-09-04 2019-12-25 Cellectis Trophoblast glycoprotein (5t4, tpbg) specific chimeric antigen receptors for cancer immunotherapy
JP2017527289A (ja) * 2014-09-04 2017-09-21 セレクティスＣｅｌｌｅｃｔｉｓ 癌免疫療法のための栄養膜糖タンパク質（５ｔ４、ｔｐｂｇ）特異的キメラ抗原受容体
US10759868B2 (en) 2014-09-04 2020-09-01 Cellectis Trophoblast glycoprotein (5T4, TPBG) specific chimeric antigen receptors for cancer immunotherapy
WO2016034666A1 (en) * 2014-09-04 2016-03-10 Cellectis Trophoblast glycoprotein (5t4, tpbg) specific chimeric antigen receptors for cancer immunotherapy
JP7222954B2 (ja) 2014-09-04 2023-02-15 セレクティス 癌免疫療法のための栄養膜糖タンパク質（５ｔ４、ｔｐｂｇ）特異的キメラ抗原受容体
EP3699188A1 (en) * 2014-09-04 2020-08-26 Cellectis 5t4 (tpbg) specific chimeric antigen receptors for cancer immunotherapy
AU2015310897B2 (en) * 2014-09-04 2020-03-19 Cellectis Trophoblast glycoprotein (5T4, tpbg) specific chimeric antigen receptors for cancer immunotherapy
JP2021006033A (ja) * 2014-09-04 2021-01-21 セレクティスＣｅｌｌｅｃｔｉｓ 癌免疫療法のための栄養膜糖タンパク質（５ｔ４、ｔｐｂｇ）特異的キメラ抗原受容体
EP3967709A1 (en) 2014-09-17 2022-03-16 Novartis AG Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy
WO2016044605A1 (en) 2014-09-17 2016-03-24 Beatty, Gregory Targeting cytotoxic cells with chimeric receptors for adoptive immunotherapy
US20200318069A1 (en) * 2014-09-19 2020-10-08 City Of Hope COSTIMULATORY CHIMERIC ANTIGEN RECEPTOR T CELLS TARGETING IL13R-alpha-2
JP7527049B2 (ja) 2014-10-09 2024-08-02 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
JP2024150546A (ja) * 2014-10-09 2024-10-23 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
JP2023116674A (ja) * 2014-10-09 2023-08-22 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
RU2670147C1 (ru) * 2014-10-09 2018-10-18 Ямагути Юниверсити Вектор экспрессии car и car-экспрессирующие т-клетки
TWI688651B (zh) * 2014-10-09 2020-03-21 日商諾伊爾免疫生物科技股份有限公司 Ｃａｒ表現載體及ｃａｒ表現ｔ細胞
JP2020108398A (ja) * 2014-10-09 2020-07-16 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
JPWO2016056228A1 (ja) * 2014-10-09 2017-06-01 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
US10316102B2 (en) 2014-10-09 2019-06-11 Yamaguchi University Car expression vector and car-expressing T cells
JP7755890B2 (ja) 2014-10-09 2025-10-17 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
JP7300763B2 (ja) 2014-10-09 2023-06-30 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
CN107109421B (zh) * 2014-10-09 2018-09-25 国立大学法人山口大学 Car表达载体及car表达t细胞
JP7008350B2 (ja) 2014-10-09 2022-02-10 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
US10906984B2 (en) 2014-10-09 2021-02-02 Yamaguchi University CAR expression vector and CAR-expressing T cells
JP2022048153A (ja) * 2014-10-09 2022-03-25 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
JP2017153487A (ja) * 2014-10-09 2017-09-07 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
WO2016056228A1 (ja) * 2014-10-09 2016-04-14 国立大学法人山口大学 Ｃａｒ発現ベクター及びｃａｒ発現ｔ細胞
CN107109421A (zh) * 2014-10-09 2017-08-29 国立大学法人山口大学 Car表达载体及car表达t细胞
US20170246278A1 (en) * 2014-10-17 2017-08-31 Baylor College Of Medicine Bipartite and tripartite signaling immune cells
WO2016064929A1 (en) 2014-10-20 2016-04-28 Juno Therapeutics, Inc. Methods and compositions for dosing in adoptive cell therapy
US10507219B2 (en) 2014-10-20 2019-12-17 Juno Therapeutics, Inc. Methods and compositions for dosing in adoptive cell therapy
EP3932950A1 (en) 2014-10-20 2022-01-05 Juno Therapeutics, Inc. Methods and compositions for dosing in adoptive cell therapy
US11633426B2 (en) 2014-10-20 2023-04-25 Juno Therapeutics, Inc. Methods and compositions for dosing in adoptive cell therapy
US11471487B2 (en) 2014-10-31 2022-10-18 The Trustees Of The University Of Pennsylvania Compositions and methods of stimulating and expanding T cells
AU2015339106B2 (en) * 2014-10-31 2020-07-02 The Trustees Of The University Of Pennsylvania Compositions and methods of stimulating and expanding T cells
JP2017533707A (ja) * 2014-10-31 2017-11-16 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア Ｔ細胞を刺激および拡大する組成物および方法
US20170258835A1 (en) * 2014-10-31 2017-09-14 The Trustees Of The University Of Pennsylvania Methods and compositions for modified t cells
WO2016070061A1 (en) * 2014-10-31 2016-05-06 The Trustees Of The University Of Pennsylvania Methods and compositions for modified t cells
EP4407036A2 (en) 2014-11-05 2024-07-31 Juno Therapeutics, Inc. Methods for transduction and cell processing
US11802295B2 (en) 2014-11-05 2023-10-31 Juno Therapeutics, Inc. Methods for transduction and cell processing
EP3757206A1 (en) 2014-11-05 2020-12-30 Juno Therapeutics, Inc. Methods for transduction and cell processing
WO2016073602A2 (en) 2014-11-05 2016-05-12 Juno Therapeutics, Inc. Methods for transduction and cell processing
US10428351B2 (en) 2014-11-05 2019-10-01 Juno Therapeutics, Inc. Methods for transduction and cell processing
WO2016090034A2 (en) 2014-12-03 2016-06-09 Novartis Ag Methods for b cell preconditioning in car therapy
EP3766895A1 (en) 2014-12-03 2021-01-20 Juno Therapeutics, Inc. Methods and compositions for adoptive cell therapy
US11266739B2 (en) 2014-12-03 2022-03-08 Juno Therapeutics, Inc. Methods and compositions for adoptive cell therapy
WO2016090190A1 (en) 2014-12-03 2016-06-09 Juno Therapeutics, Inc. Methods and compositions for adoptive cell therapy
WO2016090034A3 (en) * 2014-12-03 2016-08-04 Novartis Ag Methods for b cell preconditioning in car therapy
US12497440B2 (en) 2014-12-05 2025-12-16 City Of Hope CS1 targeted chimeric antigen receptor-modified T cells
KR102558502B1 (ko) 2014-12-05 2023-07-20 시티 오브 호프 Ｃｓ1 표적화된 키메라 항원 수용체-변형된 ｔ 세포
JP7252379B2 (ja) 2014-12-05 2023-04-04 シティ・オブ・ホープ Ｃｓ１標的化キメラ抗原受容体修飾ｔ細胞
WO2016090369A1 (en) * 2014-12-05 2016-06-09 City Of Hope Cs1 targeted chimeric antigen receptor-modified t cells
CN107429253A (zh) * 2014-12-05 2017-12-01 希望之城公司 Cs1靶向性嵌合抗原受体修饰的t细胞
CN107429253B (zh) * 2014-12-05 2021-11-05 希望之城公司 Cs1靶向性嵌合抗原受体修饰的t细胞
US11730797B2 (en) 2014-12-05 2023-08-22 City Of Hope CS1 targeted chimeric antigen receptor-modified T cells
CN114085856A (zh) * 2014-12-05 2022-02-25 希望之城公司 Cs1靶向性嵌合抗原受体修饰的t细胞
JP2017537627A (ja) * 2014-12-05 2017-12-21 シティ・オブ・ホープＣｉｔｙ ｏｆ Ｈｏｐｅ Ｃｓ１標的化キメラ抗原レセプター改変ｔ細胞
KR20170090495A (ko) * 2014-12-05 2017-08-07 시티 오브 호프 Ｃｓ1 표적화된 키메라 항원 수용체-변형된 ｔ 세포
JP7098325B2 (ja) 2014-12-05 2022-07-11 シティ・オブ・ホープ Ｃｓ１標的化キメラ抗原レセプター改変ｔ細胞
EP4219530A1 (en) * 2014-12-05 2023-08-02 City of Hope Cs1 targeted chimeric antigen receptor-modified t cells
AU2015357485B2 (en) * 2014-12-05 2020-10-15 City Of Hope CS1 targeted chimeric antigen receptor-modified T cells
US10821161B2 (en) 2014-12-05 2020-11-03 City Of Hope CS1 targeted chimeric antigen receptor-modified T cells
JP2022051744A (ja) * 2014-12-05 2022-04-01 シティ・オブ・ホープ Ｃｓ１標的化キメラ抗原受容体修飾ｔ細胞
AU2021200122B2 (en) * 2014-12-05 2023-02-23 City Of Hope CS1 Targeted Chimeric Antigen Receptor-Modified T Cells
US11160833B2 (en) 2014-12-15 2021-11-02 The Regents Of The University Of California Bispecific OR-gate chimeric antigen receptor responsive to CD19 and CD20
US12053491B2 (en) 2014-12-15 2024-08-06 The Regents Of The University Of California Bispecific OR-gate chimeric antigen receptor responsive to CD19 and CD20
EP4400516A1 (en) * 2014-12-15 2024-07-17 The Regents of the University of California Bispecific or-gate chimeric antigen receptor responsive to cd19 and cd20
US11253546B2 (en) 2014-12-15 2022-02-22 The Regents Of The University Of California Bispecific OR-gate chimeric antigen receptor responsive to CD19 and CD20
US12570968B2 (en) 2014-12-15 2026-03-10 The Regents Of The University Of California Cytotoxic molecules responsive to intracellular ligands for selective T cell mediated killing
US11384350B2 (en) 2014-12-15 2022-07-12 The Regents Of The University Of California Cytotoxic molecules responsive to intracellular ligands for selective T cell mediated killing
US12233090B2 (en) 2014-12-15 2025-02-25 The Regents Of The University Of California Bispecific or-gate chimeric antigen receptor responsive to CD20 and CD19
WO2016100232A1 (en) * 2014-12-15 2016-06-23 The Regents Of The University Of California Bispecific or-gate chimeric antigen receptor responsive to cd19 and cd20
US12226435B2 (en) 2014-12-15 2025-02-18 The Regents Of The University Of California Bispecific OR-gate chimeric antigen receptor responsive to CD20 and CD19
JP2018504894A (ja) * 2014-12-19 2018-02-22 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド キメラ抗原受容体およびその使用方法
JP2024163140A (ja) * 2014-12-19 2024-11-21 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド キメラ抗原受容体およびその使用方法
JP7833003B2 (ja) 2014-12-19 2026-03-18 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド キメラ抗原受容体およびその使用方法
US12195514B2 (en) 2014-12-19 2025-01-14 Dana-Farber Cancer Institute, Inc. Chimeric antigen receptors and methods of use thereof
US11034750B2 (en) 2014-12-24 2021-06-15 Autolus Limited Chimeric antigen receptor (CAR) comprising a CD19-binding domain
JP2020022508A (ja) * 2014-12-24 2020-02-13 ユーシーエル ビジネス リミテッド 細胞
EP3237442B1 (en) 2014-12-24 2019-07-10 UCL Business PLC Cell
KR102085349B1 (ko) * 2014-12-24 2020-03-06 유씨엘 비즈니스 리미티드 세포
US10098926B2 (en) 2014-12-24 2018-10-16 Ucl Business Plc Cell
WO2016102965A1 (en) * 2014-12-24 2016-06-30 Ucl Business Plc Cell
JP2018501794A (ja) * 2014-12-24 2018-01-25 ユーシーエル ビジネス ピーエルシー 細胞
US12398194B2 (en) 2014-12-24 2025-08-26 Autolus Limited Cell lexpressing two chimeric antigen receptors (CARs) at the cell surface
JP2022002546A (ja) * 2014-12-24 2022-01-11 オートラス リミテッド 細胞
KR20170092695A (ko) * 2014-12-24 2017-08-11 유씨엘 비즈니스 피엘씨 세포
US10174099B2 (en) 2014-12-24 2019-01-08 Ucl Business Plc Cell
US10981970B2 (en) 2014-12-24 2021-04-20 Autolus Limited Chimeric antigen receptor (CAR) comprising a CD22-binding domain
CN107002045B (zh) * 2014-12-24 2025-10-21 奥托路斯有限公司 细胞
US11091532B2 (en) 2014-12-24 2021-08-17 Autolus Limited T cell which co-expresses a CD19 chimeric antigen receptor and a CD22 chimeric antigen receptor
CN107002045A (zh) * 2014-12-24 2017-08-01 Ucl商务股份有限公司 细胞
WO2016109668A1 (en) * 2014-12-31 2016-07-07 Anthrogenesis Corporation Methods of treating hematological disorders, solid tumors, or infectious diseases using natural killer cells
WO2016115177A1 (en) 2015-01-12 2016-07-21 Juno Therapeutics, Inc. Modified hepatitis post-transcriptional regulatory elements
US10363269B2 (en) 2015-01-12 2019-07-30 Juno Therapeutics, Inc. Modified hepatitis post-transcriptional regulatory elements
WO2016115559A1 (en) 2015-01-16 2016-07-21 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for ror1
US10889652B2 (en) 2015-01-16 2021-01-12 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for ROR1
US11919970B2 (en) 2015-01-16 2024-03-05 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for ROR1
EP3760644A1 (en) 2015-01-16 2021-01-06 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for ror1
US11014989B2 (en) 2015-01-26 2021-05-25 Cellectis Anti-CLL1 specific single-chain chimeric antigen receptors (scCARs) for cancer immunotherapy
WO2016126608A1 (en) 2015-02-02 2016-08-11 Novartis Ag Car-expressing cells against multiple tumor antigens and uses thereof
CN105985444B (zh) * 2015-02-05 2024-02-13 博生吉安科细胞技术有限公司 一种嵌合抗原受体、以及快速构建嵌合抗原受体的方法及应用
CN105985444A (zh) * 2015-02-05 2016-10-05 博生吉医药科技(苏州)有限公司 一种嵌合抗原受体、以及快速构建嵌合抗原受体的方法及应用
US10647778B2 (en) 2015-02-09 2020-05-12 University Of Florida Research Foundation, Incorporated Bi-specific chimeric antigen receptor and uses thereof
US11248058B2 (en) 2015-02-19 2022-02-15 University Of Florida Research Foundation, Inc. Chimeric antigen receptors and uses thereof
US20210054346A1 (en) * 2015-02-24 2021-02-25 Board Of Regents, The University Of Texas System Selection methods for genetically-modified t cells
WO2016141357A1 (en) * 2015-03-05 2016-09-09 Fred Hutchinson Cancer Research Center Immunomodulatory fusion proteins and uses thereof
US12012443B2 (en) 2015-03-05 2024-06-18 Fred Hutchinson Cancer Center Immunomodulatory fusion proteins and uses thereof
JP2018508219A (ja) * 2015-03-05 2018-03-29 フレッド ハッチンソン キャンサー リサーチ センター 免疫調節性融合タンパク質およびその使用
AU2016226022B2 (en) * 2015-03-05 2020-07-09 Fred Hutchinson Cancer Center Immunomodulatory fusion proteins and uses thereof
AU2020244495B2 (en) * 2015-03-05 2022-12-01 Fred Hutchinson Cancer Center Immunomodulatory fusion proteins and uses thereof
CN107531805A (zh) * 2015-03-05 2018-01-02 弗雷德哈钦森癌症研究中心 免疫调节融合蛋白及其用途
RU2755227C2 (ru) * 2015-03-05 2021-09-14 Фред Хатчинсон Кансэр Рисёч Сентер Иммуномодулирующие слитые белки и пути их применения
EP4406604A3 (en) * 2015-03-05 2024-10-23 Fred Hutchinson Cancer Center Immunomodulatory fusion proteins and uses thereof
JP7026161B2 (ja) 2015-03-05 2022-02-25 フレッド ハッチンソン キャンサー リサーチ センター 免疫調節性融合タンパク質およびその使用
JP2020114264A (ja) * 2015-03-05 2020-07-30 フレッド ハッチンソン キャンサー リサーチ センター 免疫調節性融合タンパク質およびその使用
US10738116B2 (en) 2015-03-19 2020-08-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Dual specific anti-CD22-anti-CD19 chimeric antigen receptors
US10800828B2 (en) 2015-03-26 2020-10-13 The Scripps Research Institute Switchable non-scFv chimeric receptors, switches, and methods of use thereof to treat cancer
EA039192B1 (ru) * 2015-03-30 2021-12-16 Селджин Корпорейшн Способ лечения рака и набор для лечения рака
IL254817B2 (en) * 2015-04-08 2023-12-01 Novartis Ag Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car) - expressing cell
US12344657B2 (en) 2015-04-08 2025-07-01 Novartis Ag CD20 therapies, CD22 therapies, and combination therapies with a CD19 chimeric antigen receptor (CAR)-expressing cell
TWI746437B (zh) * 2015-04-08 2021-11-21 瑞士商諾華公司 Ｃｄ２０療法、ｃｄ２２療法及與表現ｃｄ１９嵌合抗原受體（ｃａｒ）之細胞的組合療法
IL254817B1 (en) * 2015-04-08 2023-08-01 Novartis Ag cd20 treatments, cd22 treatments and combined treatments with a chimeric antigen receptor expressing cell cd19
EP4491715A3 (en) * 2015-04-08 2025-06-18 Novartis AG Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car)- expressing cell
US11149076B2 (en) 2015-04-08 2021-10-19 Novartis Ag CD20 therapies, CD22 therapies, and combination therapies with a CD19 chimeric antigen receptor (CAR)-expressing cell
WO2016164731A3 (en) * 2015-04-08 2016-11-10 Novartis Ag Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car) - expressing cell
CN114958764A (zh) * 2015-04-08 2022-08-30 诺华股份有限公司 Cd20疗法、cd22疗法和与cd19嵌合抗原受体（car）表达细胞的联合疗法
CN108350058A (zh) * 2015-04-08 2018-07-31 诺华股份有限公司 Cd20疗法、cd22疗法和与cd19嵌合抗原受体(car)表达细胞的联合疗法
JP2018518939A (ja) * 2015-04-08 2018-07-19 ノバルティス アーゲー Ｃｄ２０療法、ｃｄ２２療法、およびｃｄ１９キメラ抗原受容体（ｃａｒ）発現細胞との併用療法
CN108350058B (zh) * 2015-04-08 2022-03-18 诺华股份有限公司 Cd20疗法、cd22疗法和与cd19嵌合抗原受体(car)表达细胞的联合疗法
US10253086B2 (en) 2015-04-08 2019-04-09 Novartis Ag CD20 therapies, CD22 therapies, and combination therapies with a CD19 chimeric antigen receptor (CAR)-expressing cell
US11091546B2 (en) 2015-04-15 2021-08-17 The Scripps Research Institute Optimized PNE-based chimeric receptor T cell switches and uses thereof
WO2016166568A1 (en) 2015-04-16 2016-10-20 Juno Therapeutics Gmbh Methods, kits and apparatus for expanding a population of cells
US10786549B2 (en) 2015-04-23 2020-09-29 Baylor College Of Medicine CD5 chimeric antigen receptor for adoptive T cell therapy
EP3286225A4 (en) * 2015-04-23 2018-10-10 Baylor College of Medicine Cd5 chimeric antigen receptor for adoptive t cell therapy
WO2016172583A1 (en) 2015-04-23 2016-10-27 Novartis Ag Treatment of cancer using chimeric antigen receptor and protein kinase a blocker
WO2016172606A1 (en) 2015-04-23 2016-10-27 Baylor College Of Medicine Cd5 chimeric antigen receptor for adoptive t cell therapy
WO2016174405A1 (en) * 2015-04-27 2016-11-03 Ucl Business Plc Nucleic acid construct for expressing more than one chimeric antigen receptor
US11827904B2 (en) 2015-04-29 2023-11-28 Fred Hutchinson Cancer Center Modified stem cells and uses thereof
US20200277400A1 (en) * 2015-05-15 2020-09-03 City Of Hope Chimeric antigen receptor compositions
CN108137669B (zh) * 2015-05-18 2023-02-17 优瑞科生物技术公司 抗ror1嵌合抗原受体
WO2016185035A1 (en) * 2015-05-20 2016-11-24 Cellectis Anti-gd3 specific chimeric antigen receptors for cancer immunotherapy
US10752670B2 (en) 2015-05-20 2020-08-25 Cellectis Anti-GD3 specific chimeric antigen receptors for cancer immunotherapy
WO2016196388A1 (en) 2015-05-29 2016-12-08 Juno Therapeutics, Inc. Composition and methods for regulating inhibitory interactions in genetically engineered cells
CN107849112B (zh) * 2015-06-25 2022-04-01 美商生物细胞基因治疗有限公司 嵌合抗原受体(car)、组合物及其使用方法
CN107849112A (zh) * 2015-06-25 2018-03-27 美商生物细胞基因治疗有限公司 嵌合抗原受体(car)、组合物及其使用方法
WO2016210447A1 (en) * 2015-06-26 2016-12-29 University Of Southern California Masking chimeric antigen receptor t cells for tumor-specific activation
CN107709356A (zh) * 2015-06-26 2018-02-16 南加利福尼亚大学 用于肿瘤特异性活化的掩蔽嵌合抗原受体t细胞
US10822419B2 (en) 2015-06-26 2020-11-03 University Of Southern California Masking chimeric antigen receptor T cells for tumor-specific activation
US10786533B2 (en) 2015-07-15 2020-09-29 Juno Therapeutics, Inc. Engineered cells for adoptive cell therapy
US12018077B2 (en) 2015-07-31 2024-06-25 Memorial Sloan-Kettering Cancer Center Methods of treatments using antigen-binding proteins targeting CD56
US10730941B2 (en) 2015-07-31 2020-08-04 Memorial Sloan-Kettering Cancer Center Antigen-binding proteins targeting CD56 and uses thereof
EP3328994A4 (en) * 2015-07-31 2019-04-17 Memorial Sloan-Kettering Cancer Center CD56-Faced Antigen-Binding Proteins and Uses Thereof
US11458167B2 (en) 2015-08-07 2022-10-04 Seattle Children's Hospital Bispecific CAR T-cells for solid tumor targeting
WO2017027392A1 (en) 2015-08-07 2017-02-16 Novartis Ag Treatment of cancer using chimeric cd3 receptor proteins
CN108174604A (zh) * 2015-08-07 2018-06-15 西雅图儿童医院（Dba西雅图儿童研究所） 用于实体瘤靶向的双特异性car t细胞
EP3331920A4 (en) * 2015-08-07 2019-04-03 Seattle Children's Hospital, dba Seattle Children's Research Institute BIS SPECIFIC CAR T CELLS FOR TARGETING OF SOLID TUMORS
US11123369B2 (en) 2015-08-07 2021-09-21 Seattle Children's Hospital Bispecific CAR T-cells for solid tumor targeting
AU2016306209B2 (en) * 2015-08-07 2023-07-06 Seattle Children's Hospital (dba Seattle Children's Research Institute) Bispecific CAR T-cells for solid tumor targeting
CN113234173B (zh) * 2015-08-11 2022-03-11 南京传奇生物科技有限公司 靶向bcma的嵌合抗原受体及其使用方法
AU2020200151C1 (en) * 2015-08-11 2022-09-08 Legend Biotech Ireland Limited Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
IL257297B (en) * 2015-08-11 2022-08-01 Legend Biotech Ireland Ltd Chimeric Antigen Receptors Based on Single-Site Antibodies and Methods for Using Them
WO2017025038A1 (en) 2015-08-11 2017-02-16 Nanjing Legend Biotech Co., Ltd. Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
EP3334765A4 (en) * 2015-08-11 2019-05-08 Legend Biotech Ireland Limited CHIMERIC ANTIGEN RECEPTORS BASED ON INDIVIDUAL DOMAIN ANTIBODIES AND METHOD FOR USE THEREOF
EP4063397A1 (en) * 2015-08-11 2022-09-28 Legend Biotech Ireland Limited Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
US10934363B2 (en) 2015-08-11 2021-03-02 Legend Biotech Usa Inc. Chimeric antigen receptors based on single domain antibodies and methods of use thereof
CN109311999A (zh) * 2015-08-11 2019-02-05 南京传奇生物科技有限公司 基于单结构域抗体的嵌合抗原受体及其使用方法
EP4424376A3 (en) * 2015-08-11 2024-12-04 Legend Biotech Ireland Limited Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
US10988540B2 (en) 2015-08-11 2021-04-27 Osaka University Antibody
AU2020200151B2 (en) * 2015-08-11 2022-03-17 Legend Biotech Ireland Limited Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
US10654931B2 (en) 2015-08-11 2020-05-19 Osaka University Antibody
CN113234173A (zh) * 2015-08-11 2021-08-10 南京传奇生物科技有限公司 靶向bcma的嵌合抗原受体及其使用方法
CN105384825A (zh) * 2015-08-11 2016-03-09 南京传奇生物科技有限公司 一种基于单域抗体的双特异性嵌合抗原受体及其应用
WO2017029512A1 (en) * 2015-08-20 2017-02-23 Autolus Ltd Chimeric cytokine receptor
EP4338756A3 (en) * 2015-08-20 2024-06-05 Autolus Limited Chimeric cytokine receptor
EP3438123A1 (en) * 2015-08-20 2019-02-06 Autolus Limited Chimeric cytokine receptor
US11365262B2 (en) 2015-08-20 2022-06-21 Autolus Limited Cell
US10800854B2 (en) 2015-08-20 2020-10-13 Autolus Limited Chimeric cytokine receptors and encoding nucleic acids
US10800855B2 (en) 2015-08-20 2020-10-13 Autolus Limited Chimeric cytokine receptors and encoding nucleic acids
US12234295B2 (en) 2015-08-20 2025-02-25 Autolus Limited Chimeric transmembrane protein comprising antibody dimerization domains and a type I cytokine receptor endodomain, encoding nucleic acids thereof and methods of use thereof
US11479614B2 (en) 2015-08-20 2022-10-25 Autolus Limited Methods for treating cancer or modulating T cells or NK cells in a subject with cancer by administering cells comprising chimeric cytokine receptors
US11479613B2 (en) 2015-08-20 2022-10-25 Autolus Limited Methods for treating cancer or modulating T cells or NK cells in a subject by administering cells comprising chimeric transmembrane proteins
US12122820B2 (en) 2015-09-22 2024-10-22 The Trustees Of The University Of Pennsylvania Method of redirecting t cells to treat HIV infection
EP3662930A1 (en) 2015-09-24 2020-06-10 AbVitro LLC Hiv antibody compositions and methods of use
WO2017053906A1 (en) 2015-09-24 2017-03-30 Abvitro Llc Hiv antibody compositions and methods of use
WO2017053902A1 (en) 2015-09-25 2017-03-30 Abvitro Llc High throughput process for t cell receptor target identification of natively-paired t cell receptor sequences
WO2017059900A1 (en) * 2015-10-07 2017-04-13 Biontech Cell & Gene Therapies Gmbh Antigen receptors and uses thereof
KR20180057648A (ko) * 2015-10-07 2018-05-30 비온테크 쎌 & 제네 테라피스 게엠베하 항원 수용체 및 그의 용도
WO2017060300A1 (en) * 2015-10-07 2017-04-13 Biontech Cell & Gene Therapies Gmbh Antigen receptors and uses thereof
KR102084173B1 (ko) 2015-10-07 2020-03-03 비온테크 쎌 & 제네 테라피스 게엠베하 항원 수용체 및 그의 용도
RU2792042C2 (ru) * 2015-10-07 2023-03-16 Бионтэк Селл & Гене Терапиез Гмбх Антигенные рецепторы и их применения
WO2017068425A1 (en) 2015-10-22 2017-04-27 Juno Therapeutics Gmbh Methods for culturing cells and kits and apparatus for same
WO2017068421A1 (en) 2015-10-22 2017-04-27 Juno Therapeutics Gmbh Methods for culturing cells and kits and apparatus for same
US11248238B2 (en) 2015-10-22 2022-02-15 Juno Therapeutics Gmbh Methods, kits, agents and apparatuses for transduction
WO2017068419A2 (en) 2015-10-22 2017-04-27 Juno Therapeutics Gmbh Methods, kits, agents and apparatuses for transduction
US11913024B2 (en) 2015-10-22 2024-02-27 Juno Therapeutics Gmbh Methods for culturing cells and kits and apparatus for same
US12129477B2 (en) 2015-10-22 2024-10-29 Juno Therapeutics Gmbh Methods, kits, agents and apparatuses for transduction
US11466253B2 (en) 2015-10-22 2022-10-11 Juno Therapeutics Gmbh Methods for culturing cells and kits and apparatus for same
US11014980B2 (en) 2015-10-30 2021-05-25 The Regents Of The University Of California Transforming growth factor-beta-responsive polypeptides and their methods for use
CN108884155B (zh) * 2015-10-30 2022-12-06 加利福尼亚大学董事会 转化生长因子-β应答多肽及其使用方法
US12590145B2 (en) 2015-10-30 2026-03-31 The Regents Of The University Of California Bi-specific chimeric antigen receptor
CN115960264A (zh) * 2015-10-30 2023-04-14 加利福尼亚大学董事会 转化生长因子-β应答多肽及其使用方法
WO2017075433A1 (en) 2015-10-30 2017-05-04 The Regents Of The University Of California Transforming growth factor-beta-responsive polypeptides and their methods for use
KR20180092947A (ko) * 2015-10-30 2018-08-20 더 리전츠 오브 더 유니버시티 오브 캘리포니아 형질 전환 성장 인자-베타-반응성 폴리펩티드 및 이의 사용 방법
KR102771979B1 (ko) * 2015-10-30 2025-02-21 더 리전츠 오브 더 유니버시티 오브 캘리포니아 형질 전환 성장 인자-베타-반응성 폴리펩티드 및 이의 사용 방법
EP4169945A1 (en) * 2015-10-30 2023-04-26 The Regents of the University of California Transforming growth factor-beta-responsive polypeptides and their methods for use
CN108884155A (zh) * 2015-10-30 2018-11-23 加利福尼亚大学董事会 转化生长因子-β应答多肽及其使用方法
EP3368571A4 (en) * 2015-10-30 2019-11-06 The Regents of The University of California POLYPEPTIDES APPLICABLE TO TRANSFORMING GROWTH FACTOR BETA AND METHOD OF USE THEREOF
US11020429B2 (en) 2015-11-05 2021-06-01 Juno Therapeutics, Inc. Vectors and genetically engineered immune cells expressing metabolic pathway modulators and uses in adoptive cell therapy
WO2017079705A1 (en) 2015-11-05 2017-05-11 Juno Therapeutics, Inc. Chimeric receptors containing traf-inducing domains and related compositions and methods
WO2017079703A1 (en) 2015-11-05 2017-05-11 Juno Therapeutics, Inc. Vectors and genetically engineered immune cells expressing metabolic pathway modulators and uses in adoptive cell therapy
US10035856B2 (en) * 2015-11-19 2018-07-31 Revitope Limited Functional antibody fragment complementation for a two-components system for redirected killing of unwanted cells
US20170152316A1 (en) * 2015-11-19 2017-06-01 Revitope Limited Functional antibody fragment complementation for a two-components system for redirected killing of unwanted cells
EP4458957A2 (en) 2015-11-23 2024-11-06 Novartis AG Optimized lentiviral transfer vectors and uses thereof
WO2017091786A1 (en) 2015-11-23 2017-06-01 Novartis Ag Optimized lentiviral transfer vectors and uses thereof
EP4458957A3 (en) * 2015-11-23 2025-03-05 Novartis AG Optimized lentiviral transfer vectors and uses thereof
WO2017096327A3 (en) * 2015-12-03 2017-07-13 Juno Therapeutics, Inc. Compositions and methods for reducing immune responses against chimeric antigen receptors
US12139526B2 (en) 2015-12-03 2024-11-12 Juno Therapeutics, Inc. Modified chimeric receptors and related compositions and methods
WO2017096329A1 (en) 2015-12-03 2017-06-08 Juno Therapeutics, Inc. Modified chimeric receptors and related compositions and methods
WO2017096327A2 (en) 2015-12-03 2017-06-08 Juno Therapeutics, Inc. Compositions and methods for reducing immune responses against cell therapies
EP4212166A1 (en) 2015-12-03 2023-07-19 Juno Therapeutics, Inc. Compositions and methods for reducing immune responses against cell therapies
EP4212547A1 (en) 2015-12-03 2023-07-19 Juno Therapeutics, Inc. Modified chimeric receptors and related compositions and methods
EP4012415A2 (en) 2015-12-04 2022-06-15 Juno Therapeutics, Inc. Methods and compositions related to toxicity associated with cell therapy
US11815514B2 (en) 2015-12-04 2023-11-14 Juno Therapeutics, Inc. Methods and compositions related to toxicity associated with cell therapy
WO2017114497A1 (en) 2015-12-30 2017-07-06 Novartis Ag Immune effector cell therapies with enhanced efficacy
EP4219689A2 (en) 2015-12-30 2023-08-02 Novartis AG Immune effector cell therapies with enhanced efficacy
WO2017149515A1 (en) 2016-03-04 2017-09-08 Novartis Ag Cells expressing multiple chimeric antigen receptor (car) molecules and uses therefore
WO2017161208A1 (en) 2016-03-16 2017-09-21 Juno Therapeutics, Inc. Methods for determining dosing of a therapeutic agent and related treatments
WO2017161212A1 (en) 2016-03-16 2017-09-21 Juno Therapeutics, Inc. Methods for adaptive design of a treatment regimen and related treatments
KR20240115908A (ko) 2016-03-17 2024-07-26 고쿠리츠다이가쿠호우진 야마구치 다이가쿠 면역 기능 제어 인자를 발현하는 면역 담당 세포 및 발현 벡터
US11337997B2 (en) 2016-03-17 2022-05-24 Yamaguchi University Immunocompetent cell and expression vector expressing regulatory factors of immune function
KR20200137030A (ko) 2016-03-17 2020-12-08 고쿠리츠다이가쿠호우진 야마구치 다이가쿠 면역 기능 제어 인자를 발현하는 면역 담당 세포 및 발현 벡터
US11931381B2 (en) 2016-03-17 2024-03-19 Yamaguchi University Immunocompetent cell and expression vector expressing regulatory factors of immune function
KR20180127403A (ko) 2016-03-17 2018-11-28 고쿠리츠다이가쿠호우진 야마구치 다이가쿠 면역 기능 제어 인자를 발현하는 면역 담당 세포 및 발현 벡터
EP4692328A2 (en) 2016-03-17 2026-02-11 Yamaguchi University Immunocompetent cell and expression vector expressing regulatory factors of immune function
KR20240116832A (ko) 2016-03-17 2024-07-30 고쿠리츠다이가쿠호우진 야마구치 다이가쿠 면역 기능 제어 인자를 발현하는 면역 담당 세포 및 발현 벡터
KR20230017358A (ko) 2016-03-17 2023-02-03 고쿠리츠다이가쿠호우진 야마구치 다이가쿠 면역 기능 제어 인자를 발현하는 면역 담당 세포 및 발현 벡터
US12325728B2 (en) 2016-03-19 2025-06-10 Exuma Biotech Corp. Methods and compositions for genetically modifying lymphocytes to express polypeptides comprising the intracellular domain of CD79A and CD79B
US12258574B2 (en) 2016-03-19 2025-03-25 Exuma Biotech Corp. Methods and compositions for transducing lymphocytes and regulating the activity thereof
US12590321B2 (en) 2016-03-19 2026-03-31 Exuma Biotech Corp. Methods and compositions for genetically modifying and expanding lymphocytes and regulating the activity thereof
US11325948B2 (en) 2016-03-19 2022-05-10 Exuma Biotech Corp. Methods and compositions for genetically modifying lymphocytes to express polypeptides comprising the intracellular domain of MPL
US11518814B2 (en) 2016-03-22 2022-12-06 Seattle Children's Hospital Early intervention methods to prevent or ameliorate toxicity
EP4015536A1 (en) 2016-03-22 2022-06-22 Seattle Children's Hospital (DBA Seattle Children's Research Institute) Early intervention methods to prevent or ameliorate toxicity
EP4545143A2 (en) 2016-03-22 2025-04-30 Seattle Children's Hospital (DBA Seattle Children's Research Institute) EARLY INTERVENTION METHODS TO PREVENT OR AMELIAZE TOXICITY
US12098208B2 (en) 2016-03-22 2024-09-24 Seattle Children's Hospital Early intervention methods to prevent or ameliorate toxicity
WO2017165571A1 (en) 2016-03-22 2017-09-28 Seattle Children's Hospital (dba Seattle Children's Research Institute) Early intervention methods to prevent or ameliorate toxicity
US11760804B2 (en) 2016-03-22 2023-09-19 Seattle Children's Hospital Early intervention methods to prevent or ameliorate toxicity
WO2017165683A1 (en) 2016-03-23 2017-09-28 Novartis Ag Cell secreted minibodies and uses thereof
US12144850B2 (en) 2016-04-08 2024-11-19 Purdue Research Foundation Methods and compositions for car T cell therapy
WO2017181119A2 (en) 2016-04-15 2017-10-19 Novartis Ag Compositions and methods for selective protein expression
EP4219721A2 (en) 2016-04-15 2023-08-02 Novartis AG Compositions and methods for selective protein expression
WO2017186853A1 (en) * 2016-04-27 2017-11-02 Bcrt Holding Bv T cell-based bi-specific immunotherapeutics
US11634498B2 (en) 2016-04-29 2023-04-25 University Of Florida Research Foundation, Incorporated Chimeric antigen receptors and uses thereof
WO2017193107A2 (en) 2016-05-06 2017-11-09 Juno Therapeutics, Inc. Genetically engineered cells and methods of making the same
US12311032B2 (en) 2016-05-13 2025-05-27 BioAlta, Inc. Anti-Ror2 antibodies, antibody fragments, their immunoconjugates and uses thereof
US11879011B2 (en) 2016-05-13 2024-01-23 Bioatla, Inc. Anti-ROR2 antibodies, antibody fragments, their immunoconjucates and uses thereof
EP3910059A1 (en) 2016-05-27 2021-11-17 Aadigen, Llc Peptides and nanoparticles for intracellular delivery of genome-editing molecules
WO2017205846A1 (en) 2016-05-27 2017-11-30 Aadigen, Llc Peptides and nanoparticles for intracellular delivery of genome-editing molecules
EP4011381A1 (en) 2016-06-03 2022-06-15 Memorial Sloan-Kettering Cancer Center Adoptive cell therapies as early treatment options
WO2017214207A2 (en) 2016-06-06 2017-12-14 Juno Therapeutics, Inc. Methods for the treatment of b cell malignancies using adoptive cell therapy
WO2018005556A1 (en) 2016-06-27 2018-01-04 Juno Therapeutics, Inc. Mhc-e restricted epitopes, binding molecules and related methods and uses
EP3992632A1 (en) 2016-06-27 2022-05-04 Juno Therapeutics, Inc. Mhc-e restricted epitopes, binding molecules and related methods and uses
WO2018005559A1 (en) 2016-06-27 2018-01-04 Juno Therapeutics, Inc. Method of identifying peptide epitopes, molecules that bind such epitopes and related uses
WO2018023093A1 (en) 2016-07-29 2018-02-01 Juno Therapeutics, Inc. Immunomodulatory polypeptides and related compositions and methods
WO2018023100A2 (en) 2016-07-29 2018-02-01 Juno Therapeutics, Inc. Anti-idiotypic antibodies and related methods
US12304935B2 (en) 2016-07-29 2025-05-20 Juno Therapeutics, Inc. Immunomodulatory polypeptides and related compositions and methods
WO2018023094A1 (en) 2016-07-29 2018-02-01 Juno Therapeutics, Inc. Methods for assessing the presence or absence of replication competent virus
US11421287B2 (en) 2016-07-29 2022-08-23 Juno Therapeutics, Inc. Methods for assessing the presence or absence of replication competent virus
WO2018026819A2 (en) 2016-08-01 2018-02-08 Novartis Ag Treatment of cancer using a chimeric antigen receptor in combination with an inhibitor of a pro-m2 macrophage molecule
US12350349B2 (en) 2016-08-03 2025-07-08 Washington University Gene editing of CAR-T cells for the treatment of T cell malignancies with chimeric antigen receptors
US12564648B2 (en) 2016-08-03 2026-03-03 Washington University Gene editing of CAR-T cells for the treatment of T cell malignancies with chimeric antigen receptors
US12351638B2 (en) 2016-08-10 2025-07-08 Legend Biotech Usa Inc. Chimeric antigen receptors targeting BCMA and methods of use thereof
EP3475307A4 (en) * 2016-08-10 2020-08-19 Legend Biotech Ireland Limited BCMA-TARGETING CHEMERICAL ANTIGEN RECEPTORS AND THEIR PROCEDURES FOR USE
CN109153731A (zh) * 2016-08-10 2019-01-04 南京传奇生物科技有限公司 靶向bcma的嵌合抗原受体及其使用方法
EP4282877A3 (en) * 2016-08-10 2024-02-21 Legend Biotech Ireland Limited Chimeric antigen receptors targeting bcma and methods of use thereof
US11186647B2 (en) 2016-08-10 2021-11-30 Legend Biotech Usa Inc. Chimeric antigen receptors targeting BCMA and methods of use thereof
CN109153731B (zh) * 2016-08-10 2021-04-02 南京传奇生物科技有限公司 靶向bcma的嵌合抗原受体及其使用方法
EP4282878A3 (en) * 2016-08-10 2024-03-06 Legend Biotech Ireland Limited Chimeric antigen receptors targeting bcma and methods of use thereof
EP3896091A1 (en) * 2016-08-10 2021-10-20 Legend Biotech Ireland Limited Chimeric antigen receptors targeting bcma and methods of use thereof
US11535677B2 (en) 2016-08-10 2022-12-27 Legend Biotech Usa Inc. Chimeric antigen receptors targeting BCMA and methods of use thereof
US12102652B2 (en) 2016-08-26 2024-10-01 Baylor College Of Medicine Constitutively active cytokine receptors for cell therapy
US11701384B2 (en) 2016-09-02 2023-07-18 The Regents Of The University Of California Methods and compositions involving interleukin-6 receptor alpha-binding single chain variable fragments
WO2018049420A1 (en) 2016-09-12 2018-03-15 Juno Therapeutics, Inc. Perfusion bioreactor bag assemblies
CN107841506A (zh) * 2016-09-20 2018-03-27 上海恒润达生生物科技有限公司 靶向间皮素的嵌合抗原受体及其用途
CN107841506B (zh) * 2016-09-20 2021-03-16 上海恒润达生生物科技有限公司 靶向间皮素的嵌合抗原受体及其用途
US11077178B2 (en) * 2016-09-21 2021-08-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptor (CAR) that targets chemokine receptor CCR4 and its use
US11992519B2 (en) 2016-09-21 2024-05-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptor (CAR) that targets chemokine receptor CCR4 and its use
EP3515475B1 (en) 2016-09-21 2024-05-01 The U.S.A. as represented by the Secretary, Department of Health and Human Services Chimeric antigen receptor (car) that targets chemokine receptor ccr4 and its use
AU2017332161B9 (en) * 2016-09-21 2024-08-22 The United States Government As Represented By The Department Of Veterans Affairs Chimeric antigen receptor (car) that targets chemokine receptor CCR4 and its use
EP4353319A2 (en) 2016-09-28 2024-04-17 Atossa Therapeutics, Inc. Methods of adoptive cell therapy
WO2018063985A1 (en) 2016-09-28 2018-04-05 Atossa Genetics Inc. Methods of adoptive cell therapy
US11802269B2 (en) 2016-09-30 2023-10-31 Poseida Therapeutics, Inc. Superpiggybac transposase compositions
WO2018064681A1 (en) * 2016-09-30 2018-04-05 Poseida Therapeutics, Inc. Modified stem cell memory t cells, methods of making and methods of using same
US10513686B2 (en) 2016-09-30 2019-12-24 Poseida Therapeutics, Inc. Modified stem cell memory T cells, methods of making and methods of using same
US10415016B2 (en) 2016-09-30 2019-09-17 Poseida Therapeutics, Inc. Modified stem cell memory T cells, methods of making and methods of using same
US11072660B2 (en) 2016-10-03 2021-07-27 Juno Therapeutics, Inc. HPV-specific binding molecules
WO2018067618A1 (en) 2016-10-03 2018-04-12 Juno Therapeutics, Inc. Hpv-specific binding molecules
US11026976B2 (en) 2016-10-07 2021-06-08 Novartis Ag Nucleic acid molecules encoding chimeric antigen receptors comprising a CD20 binding domain
US12594321B2 (en) 2016-10-07 2026-04-07 Novartis Ag Bispecific chimeric antigen receptor that binds CD19 and CD20, encoding nucleic acid molecules thereof and methods of use thereof to treat cancer
USRE49847E1 (en) 2016-10-07 2024-02-27 Novartis Ag Nucleic acid molecules encoding chimeric antigen receptors comprising a CD20 binding domain
US10525083B2 (en) 2016-10-07 2020-01-07 Novartis Ag Nucleic acid molecules encoding chimeric antigen receptors comprising a CD20 binding domain
US11872249B2 (en) 2016-10-07 2024-01-16 Novartis Ag Method of treating cancer by administering immune effector cells expressing a chimeric antigen receptor comprising a CD20 binding domain
EP4190335A1 (en) 2016-10-13 2023-06-07 Juno Therapeutics, Inc. Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators
WO2018071873A2 (en) 2016-10-13 2018-04-19 Juno Therapeutics, Inc. Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators
US11896615B2 (en) 2016-10-13 2024-02-13 Juno Therapeutics, Inc. Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators
WO2018071913A3 (en) * 2016-10-14 2018-05-24 Dana-Farber Cancer Institute, Inc. Modular tetravalent bispecific antibody platform
US11174306B2 (en) 2016-10-19 2021-11-16 The Scripps Research Institute Chimeric antigen receptor effector cell switches with humanized targeting moieties and/or optimized chimeric antigen receptor interacting domains and uses thereof
WO2018093591A1 (en) 2016-11-03 2018-05-24 Juno Therapeutics, Inc. Combination therapy of a cell based therapy and a microglia inhibitor
WO2018085731A2 (en) 2016-11-03 2018-05-11 Juno Therapeutics, Inc. Combination therapy of a t cell therapy and a btk inhibitor
EP4279136A2 (en) 2016-12-03 2023-11-22 Juno Therapeutics, Inc. Methods for determining car-t cells dosing
WO2018102787A1 (en) 2016-12-03 2018-06-07 Juno Therapeutics, Inc. Methods for determining car-t cells dosing
WO2018102786A1 (en) 2016-12-03 2018-06-07 Juno Therapeutics, Inc. Methods for modulation of car-t cells
WO2018102785A2 (en) 2016-12-03 2018-06-07 Juno Therapeutics, Inc. Methods and compositions for use of therapeutic t cells in combination with kinase inhibitors
US11590167B2 (en) 2016-12-03 2023-02-28 Juno Therapeutic, Inc. Methods and compositions for use of therapeutic T cells in combination with kinase inhibitors
WO2018106732A1 (en) 2016-12-05 2018-06-14 Juno Therapeutics, Inc. Production of engineered cells for adoptive cell therapy
US12358970B2 (en) 2016-12-13 2025-07-15 Seattle Children's Hospital Methods of exogenous drug activation of chemical-induced signaling complexes expressed in engineered cells in vitro and in vivo
US11753460B2 (en) 2016-12-13 2023-09-12 Seattle Children's Hospital Methods of exogenous drug activation of chemical-induced signaling complexes expressed in engineered cells in vitro and in vivo
WO2018111340A1 (en) 2016-12-16 2018-06-21 Novartis Ag Methods for determining potency and proliferative function of chimeric antigen receptor (car)-t cells
WO2018121604A1 (zh) * 2016-12-29 2018-07-05 天津天锐生物科技有限公司 一种多靶点嵌合抗原受体
CN109153730A (zh) * 2016-12-29 2019-01-04 天津天锐生物科技有限公司 一种多靶点嵌合抗原受体
EP3575325A4 (en) * 2016-12-29 2020-12-23 Timmune Biotech Inc. MULTI-TARGET CHEMICAL ANTIGEN RECEPTOR
CN109153730B (zh) * 2016-12-29 2022-04-05 深圳市北科生物科技有限公司 一种多靶点嵌合抗原受体
CN108264566A (zh) * 2016-12-30 2018-07-10 上海欣百诺生物科技有限公司 一种融合抗cd3抗体结构域和t细胞正共刺激分子配体的双特异性分子及其应用
US12161668B2 (en) 2017-01-10 2024-12-10 The General Hospital Corporation T cells expressing a chimeric antigen receptor
WO2018132518A1 (en) 2017-01-10 2018-07-19 Juno Therapeutics, Inc. Epigenetic analysis of cell therapy and related methods
US11821027B2 (en) 2017-01-10 2023-11-21 Juno Therapeutics, Inc. Epigenetic analysis of cell therapy and related methods
US11517627B2 (en) 2017-01-20 2022-12-06 Juno Therapeutics Gmbh Cell surface conjugates and related cell compositions and methods
WO2018134691A2 (en) 2017-01-20 2018-07-26 Juno Therapeutics Gmbh Cell surface conjugates and related cell compositions and methods
WO2018140725A1 (en) 2017-01-26 2018-08-02 Novartis Ag Cd28 compositions and methods for chimeric antigen receptor therapy
EP4043485A1 (en) 2017-01-26 2022-08-17 Novartis AG Cd28 compositions and methods for chimeric antigen receptor therapy
WO2018144535A1 (en) 2017-01-31 2018-08-09 Novartis Ag Treatment of cancer using chimeric t cell receptor proteins having multiple specificities
US12583903B2 (en) 2017-02-08 2026-03-24 AbelZeta Inc. Construction of chimeric antigen receptor targeting CD20 antigen and activity identification of engineered T cells thereof
US11845803B2 (en) 2017-02-17 2023-12-19 Fred Hutchinson Cancer Center Combination therapies for treatment of BCMA-related cancers and autoimmune disorders
WO2018157171A2 (en) 2017-02-27 2018-08-30 Juno Therapeutics, Inc. Compositions, articles of manufacture and methods related to dosing in cell therapy
EP4353818A2 (en) 2017-02-27 2024-04-17 Juno Therapeutics, Inc. Compositions, articles of manufacture and methods related to dosing in cell therapy
US12163952B2 (en) 2017-02-27 2024-12-10 Juno Therapeutics, Inc. Determining toxicity risk in CAR T-cell therapy
WO2018160731A1 (en) 2017-02-28 2018-09-07 Novartis Ag Shp inhibitor compositions and uses for chimeric antigen receptor therapy
US11850262B2 (en) 2017-02-28 2023-12-26 Purdue Research Foundation Compositions and methods for CAR T cell therapy
US11759480B2 (en) 2017-02-28 2023-09-19 Endocyte, Inc. Compositions and methods for CAR T cell therapy
WO2018170188A2 (en) 2017-03-14 2018-09-20 Juno Therapeutics, Inc. Methods for cryogenic storage
US11725210B2 (en) 2017-03-17 2023-08-15 Fred Hutchinson Cancer Center Immunomodulatory fusion proteins and uses thereof
US12365906B2 (en) 2017-03-17 2025-07-22 Fred Hutchinson Cancer Center Immunomodulatory fusion proteins and uses thereof
CN110382542A (zh) * 2017-03-29 2019-10-25 豪夫迈·罗氏有限公司 针对共刺激性tnf受体的双特异性抗原结合分子
US11639394B2 (en) 2017-03-29 2023-05-02 Hoffmann-La Roche Inc. Bispecific antigen binding molecule for a costimulatory TNF receptor
CN110573528A (zh) * 2017-03-29 2019-12-13 豪夫迈·罗氏有限公司 针对共刺激性tnf受体的双特异性抗原结合分子
WO2018178055A1 (en) * 2017-03-29 2018-10-04 F. Hoffmann-La Roche Ag Bispecific antigen binding molecule for a costimulatory tnf receptor
US11453722B2 (en) 2017-03-29 2022-09-27 Hoffmann La-Roche Inc. Bispecific antigen binding molecule for a costimulatory TNF receptor
WO2018178076A1 (en) * 2017-03-29 2018-10-04 F. Hoffmann-La Roche Ag Bispecific antigen binding molecule for a costimulatory tnf receptor
EP4414380A2 (en) 2017-03-31 2024-08-14 Cellectis SA Universal anti-cd22 chimeric antigen receptor engineered immune cells
WO2018178378A1 (en) 2017-03-31 2018-10-04 Cellectis Sa New universal chimeric antigen receptor t cells specific for cd22
US11690873B2 (en) 2017-03-31 2023-07-04 Cellectis Sa Universal chimeric antigen receptor T cells specific for CD22
WO2018178377A1 (en) 2017-03-31 2018-10-04 Cellectis Sa Universal anti-cd22 chimeric antigen receptor engineered immune cells
US12145994B2 (en) 2017-04-04 2024-11-19 Hoffmann-La Roche Inc. Bispecific antigen binding molecules capable of specific binding to CD40 and to fap
CN110402255B (zh) * 2017-04-04 2022-12-02 豪夫迈·罗氏有限公司 新颖的能够特异性结合cd40和fap的双特异性抗原结合分子
CN110402255A (zh) * 2017-04-04 2019-11-01 豪夫迈·罗氏有限公司 新颖的能够特异性结合cd40和fap的双特异性抗原结合分子
WO2018187791A1 (en) 2017-04-07 2018-10-11 Juno Therapeutics, Inc Engineered cells expressing prostate-specific membrane antigen (psma) or a modified form thereof and related methods
US11796534B2 (en) 2017-04-14 2023-10-24 Juno Therapeutics, Inc. Methods for assessing cell surface glycosylation
US12379375B2 (en) 2017-04-14 2025-08-05 Juno Therapeutics, Inc. Methods for assessing cell surface glycosylation
WO2018191723A1 (en) 2017-04-14 2018-10-18 Juno Therapeutics, Inc. Methods for assessing cell surface glycosylation
WO2018195175A1 (en) 2017-04-18 2018-10-25 FUJIFILM Cellular Dynamics, Inc. Antigen-specific immune effector cells
EP4083063A2 (en) 2017-04-18 2022-11-02 FUJIFILM Cellular Dynamics, Inc. Antigen-specific immune effector cells
CN108728458A (zh) * 2017-04-21 2018-11-02 上海恒润达生生物科技有限公司 靶向mesothelin的嵌合抗原受体并联合表达IL-15的方法和用途
CN108728458B (zh) * 2017-04-21 2021-11-16 上海恒润达生生物科技股份有限公司 靶向mesothelin的嵌合抗原受体并联合表达IL-15的方法和用途
US11529371B2 (en) 2017-04-24 2022-12-20 Memorial Sloan Kettering Cancer Center Anti-CD33 antibody agents
WO2018200562A1 (en) * 2017-04-24 2018-11-01 Memorial Sloan Kettering Cancer Center Anti-cd33 antibody agents
US11866465B2 (en) 2017-04-27 2024-01-09 Juno Therapeutics Gmbh Oligomeric particle reagents and methods of use thereof
EP4647493A2 (en) 2017-04-27 2025-11-12 Juno Therapeutics, Inc. Oligomeric particle reagents and methods of use thereof
WO2018197949A1 (en) 2017-04-27 2018-11-01 Juno Therapeutics Gmbh Oligomeric particle reagents and methods of use thereof
WO2018204427A1 (en) 2017-05-01 2018-11-08 Juno Therapeutics, Inc. Combination of a cell therapy and an immunomodulatory compound
EP4327878A2 (en) 2017-05-01 2024-02-28 Juno Therapeutics, Inc. Combination of a cell therapy and an immunomodulatory compound
US11980640B2 (en) 2017-05-15 2024-05-14 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Bicistronic chimeric antigen receptors and their uses
US11944647B2 (en) 2017-06-02 2024-04-02 Juno Therapeutics, Inc. Articles of manufacture and methods for treatment using adoptive cell therapy
US11413310B2 (en) 2017-06-02 2022-08-16 Juno Therapeutics, Inc. Articles of manufacture and methods for treatment using adoptive cell therapy
WO2018223098A1 (en) 2017-06-02 2018-12-06 Juno Therapeutics, Inc. Articles of manufacture and methods related to toxicity associated with cell therapy
US12583904B2 (en) 2017-06-02 2026-03-24 Juno Therapeutics, Inc. Articles of manufacture and methods for treatment using adoptive cell therapy
WO2018223101A1 (en) 2017-06-02 2018-12-06 Juno Therapeutics, Inc. Articles of manufacture and methods for treatment using adoptive cell therapy
US11740231B2 (en) 2017-06-02 2023-08-29 Juno Therapeutics, Inc. Articles of manufacture and methods related to toxicity associated with cell therapy
US12060585B2 (en) 2017-06-07 2024-08-13 Precigen, Inc. Expression of novel cell tags
CN110997920A (zh) * 2017-06-07 2020-04-10 英特拉克森公司 新型细胞标签的表达
US12180517B2 (en) 2017-06-07 2024-12-31 Precigen, Inc. Expression of novel cell tags
WO2018229715A1 (en) 2017-06-16 2018-12-20 Novartis Ag Compositions comprising anti-cd32b antibodies and methods of use thereof
EP3828264A1 (en) 2017-06-20 2021-06-02 Institut Curie Immune cells defective for suv39h1
WO2018234370A1 (en) 2017-06-20 2018-12-27 Institut Curie Immune cells defective for suv39h1
US12275787B2 (en) 2017-06-21 2025-04-15 Icell Gene Therapeutics Llc Chimeric antigen receptors (CARs), compositions and methods thereof
EP4302768A2 (en) 2017-06-22 2024-01-10 Board Of Regents, The University Of Texas System Methods for producing regulatory immune cells and uses thereof
WO2019006427A1 (en) 2017-06-29 2019-01-03 Juno Therapeutics, Inc. WALL MODEL FOR ASSESSING TOXICITIES ASSOCIATED WITH IMMUNOTHERAPIES
RU2804458C2 (ru) * 2017-07-20 2023-10-02 Аптево Рисёрч Энд Девелопмент Ллс Антигенсвязывающие белки, связывающиеся с 5t4 и 4-1bb, и относящиеся к ним композиции и способы
US11725060B2 (en) 2017-07-20 2023-08-15 Aptevo Reserch and Development LLC Antigen binding proteins binding to 5T4 and 4-1BB and related compositions and methods
WO2019014891A1 (zh) * 2017-07-20 2019-01-24 深圳普瑞金生物药业有限公司 一种用于治疗肿瘤的egfr单域抗体cart及其应用
WO2019027850A1 (en) 2017-07-29 2019-02-07 Juno Therapeutics, Inc. CELL EXPANSION REAGENTS EXPRESSING RECOMBINANT RECEPTORS
EP4549554A2 (en) 2017-07-29 2025-05-07 Juno Therapeutics, Inc. Reagents for expanding cells expressing recombinant receptors
WO2019028051A1 (en) * 2017-07-31 2019-02-07 Lentigen Technology, Inc. COMPOSITIONS AND METHODS FOR TREATING CANCER BY ANTI-CD19 / CD20 IMMUNOTHERAPY
US10442867B2 (en) 2017-07-31 2019-10-15 Lentigen Technology, Inc. Compositions and methods for treating cancer with anti-CD19/CD20 immunotherapy
CN111183156A (zh) * 2017-07-31 2020-05-19 莱蒂恩技术公司 用于用抗cd19/cd20免疫治疗来治疗癌症的组合物和方法
US11680103B2 (en) 2017-07-31 2023-06-20 Lentigen Technology, Inc. Compositions and methods for treating cancer with anti-CD19/CD20 immunotherapy
AU2018309735B2 (en) * 2017-07-31 2025-03-13 Lentigen Technology, Inc. Compositions and methods for treating cancer with anti-CD19/CD20 immunotherapy
WO2019032927A1 (en) 2017-08-09 2019-02-14 Juno Therapeutics, Inc. METHODS FOR PRODUCING GENETICALLY MODIFIED CELL COMPOSITIONS AND COMPOSITIONS THEREOF
EP4516896A2 (en) 2017-08-09 2025-03-05 Juno Therapeutics, Inc. Methods and compositions for preparing genetically engineered cells
US12215348B2 (en) 2017-08-09 2025-02-04 Juno Therapeutics, Inc. Methods for producing genetically engineered cell compositions and related compositions
US11851678B2 (en) 2017-08-09 2023-12-26 Juno Therapeutics, Inc. Methods for producing genetically engineered cell compositions and related compositions
WO2019032929A1 (en) 2017-08-09 2019-02-14 Juno Therapeutics, Inc. METHODS AND COMPOSITIONS FOR PREPARING GENETICALLY MODIFIED CELLS
WO2019046832A1 (en) 2017-09-01 2019-03-07 Juno Therapeutics, Inc. GENE EXPRESSION AND EVALUATION OF RISK OF DEVELOPMENT OF TOXICITY FOLLOWING CELL THERAPY
WO2019051335A1 (en) 2017-09-07 2019-03-14 Juno Therapeutics, Inc. METHODS OF IDENTIFYING CELLULAR CHARACTERISTICS RELATED TO RESPONSES ASSOCIATED WITH CELL THERAPY
WO2019057102A1 (en) 2017-09-20 2019-03-28 Tsinghua University HPK1 TARGETING ARNG AND HPK1 GENE EDITING METHOD
US11952408B2 (en) 2017-10-03 2024-04-09 Juno Therapeutics, Inc. HPV-specific binding molecules
EP4215543A2 (en) 2017-10-03 2023-07-26 Juno Therapeutics, Inc. Hpv-specific binding molecules
WO2019070856A1 (en) * 2017-10-03 2019-04-11 Precision Biosciences, Inc. MODIFIED EPIDERMAL GROWTH FACTOR RECEPTOR PEPTIDES FOR USE IN GENETICALLY MODIFIED CELLS
WO2019070541A1 (en) 2017-10-03 2019-04-11 Juno Therapeutics, Inc. HPV-SPECIFIC BINDING MOLECULES
EP4269560A3 (en) * 2017-10-03 2024-01-17 Precision Biosciences, Inc. Modified epidermal growth factor receptor peptides for use in genetically-modified cells
EP4265634A2 (en) 2017-10-10 2023-10-25 National University Corporation Tottori University Enhancer for t-cells or b-cells having memory function, malignant tumor recurrence inhibitor, and inducer for inducing memory function in t-cells or b-cells
US11617765B2 (en) 2017-10-10 2023-04-04 Yamaguchi University Enhancer for T-cells or B-cells having memory function, malignant tumor recurrence inhibitor, and inducer for inducing memory function in T-cells or B-cells
WO2019073973A1 (ja) 2017-10-10 2019-04-18 国立大学法人山口大学 メモリー機能を有するｔ細胞又はｂ細胞の増強剤、悪性腫瘍再発抑制剤、及びｔ細胞又はｂ細胞にメモリー機能を誘導する誘導剤
US11643472B2 (en) 2017-10-12 2023-05-09 Mcmaster University T cell-antigen coupler with Y182T mutation and methods and uses thereof
US11970545B2 (en) 2017-10-12 2024-04-30 Mcmaster University T cell-antigen coupler with Y182T mutation and methods of uses thereof
US11198737B2 (en) 2017-10-12 2021-12-14 Mcmaster University T cell-antigen coupler with Y177 mutation and methods of uses thereof
EP3694872A1 (en) 2017-10-12 2020-08-19 Board Of Regents, The University Of Texas System T cell receptors for immunotherapy
WO2019079569A1 (en) 2017-10-18 2019-04-25 Novartis Ag COMPOSITIONS AND METHODS FOR SELECTIVE DEGRADATION OF A PROTEIN
US10329543B2 (en) 2017-10-23 2019-06-25 Poseida Therapeutics, Inc. Modified stem cell memory T cells, methods of making and methods of using same
WO2019084288A1 (en) 2017-10-25 2019-05-02 Novartis Ag METHODS FOR DESIGNING CHIMERIC ANTIGENIC RECEPTOR EXPRESSION CELLS
WO2019081983A1 (en) 2017-10-25 2019-05-02 Novartis Ag CD32B TARGETING ANTIBODIES AND METHODS OF USE
US11008294B2 (en) 2017-10-30 2021-05-18 Neuropore Therapies, Inc. Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof
US11708338B2 (en) 2017-10-30 2023-07-25 Neuropore Therapies, Inc. Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof
WO2019089798A1 (en) 2017-10-31 2019-05-09 Novartis Ag Anti-car compositions and methods
WO2019090003A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Chimeric antigen receptors specific for b-cell maturation antigen (bcma)
US11851679B2 (en) 2017-11-01 2023-12-26 Juno Therapeutics, Inc. Method of assessing activity of recombinant antigen receptors
WO2019089855A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Process for generating therapeutic compositions of engineered cells
WO2019089884A2 (en) 2017-11-01 2019-05-09 Editas Medicine, Inc. Methods, compositions and components for crispr-cas9 editing of tgfbr2 in t cells for immunotherapy
WO2019089982A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Method of assessing activity of recombinant antigen receptors
US12168027B2 (en) 2017-11-01 2024-12-17 Juno Therapeutics, Inc. Methods associated with tumor burden for assessing response to a cell therapy
WO2019089969A2 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for b-cell maturation antigen
US11623961B2 (en) 2017-11-01 2023-04-11 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for B-cell maturation antigen
WO2019090004A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Process for producing a t cell composition
US12258580B2 (en) 2017-11-01 2025-03-25 Juno Therapeutics, Inc. Process for generating therapeutic compositions of engineered cells
WO2019089848A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Methods associated with tumor burden for assessing response to a cell therapy
US11564946B2 (en) 2017-11-01 2023-01-31 Juno Therapeutics, Inc. Methods associated with tumor burden for assessing response to a cell therapy
US12031975B2 (en) 2017-11-01 2024-07-09 Juno Therapeutics, Inc. Methods of assessing or monitoring a response to a cell therapy
WO2019089858A2 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Methods of assessing or monitoring a response to a cell therapy
US12428486B2 (en) 2017-11-01 2025-09-30 Juno Therapeutics, Inc. Chimeric antigen receptors specific for B-cell maturation antigen and encoding polynucleotides
US11066475B2 (en) 2017-11-01 2021-07-20 Juno Therapeutics, Inc. Chimeric antigen receptors specific for B-cell maturation antigen and encoding polynucleotides
EP4512823A2 (en) 2017-11-01 2025-02-26 Juno Therapeutics, Inc. Process for generating therapeutic compositions of engineered cells
US12193994B2 (en) 2017-11-06 2025-01-14 Juno Therapeutics, Inc. Combination of a cell therapy and a gamma secretase inhibitor
WO2019090202A1 (en) 2017-11-06 2019-05-09 Editas Medicine, Inc. Methods, compositions and components for crispr-cas9 editing of cblb in t cells for immunotherapy
WO2019090364A1 (en) 2017-11-06 2019-05-09 Juno Therapeutics, Inc. Combination of a cell therapy and a gamma secretase inhibitor
WO2019094835A1 (en) 2017-11-10 2019-05-16 Juno Therapeutics, Inc. Closed-system cryogenic vessels
WO2019094482A1 (en) * 2017-11-10 2019-05-16 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting tumor antigens
EP3707160A1 (en) * 2017-11-10 2020-09-16 The U.S.A. as represented by the Secretary, Department of Health and Human Services Chimeric antigen receptors targeting tumor antigens
US11802163B2 (en) 2017-11-10 2023-10-31 The U.S.A., As Represented By The Secretary, Department Of Health And Human Services Chimeric antigen receptors targeting glypican-3 or mesothelin
CN108034669B (zh) * 2017-11-17 2021-07-30 山东兴瑞生物科技有限公司 一种抗vegf基因、及利用其修饰的t细胞、制备方法和应用
CN108034669A (zh) * 2017-11-17 2018-05-15 山东兴瑞生物科技有限公司 一种抗vegf基因、及利用其修饰的t细胞、制备方法和应用
US20200360432A1 (en) * 2017-11-24 2020-11-19 Autolus Limited Polypeptide
US11648274B2 (en) * 2017-11-24 2023-05-16 Autolus Limited Polypeptide
WO2019109053A1 (en) 2017-12-01 2019-06-06 Juno Therapeutics, Inc. Methods for dosing and for modulation of genetically engineered cells
WO2019113557A1 (en) 2017-12-08 2019-06-13 Juno Therapeutics, Inc. Process for producing a composition of engineered t cells
US12553024B2 (en) 2017-12-08 2026-02-17 Juno Therapeutics, Inc. Serum-free media formulation for culturing cells and methods of use thereof
WO2019113556A1 (en) 2017-12-08 2019-06-13 Juno Therapeutics, Inc. Serum-free media formulation for culturing cells and methods of use thereof
WO2019113559A2 (en) 2017-12-08 2019-06-13 Juno Therapeutics, Inc. Phenotypic markers for cell therapy and related methods
US12161670B2 (en) 2017-12-08 2024-12-10 Juno Therapeutics, Inc. Phenotypic markers for cell therapy and related methods
US12577285B2 (en) 2017-12-08 2026-03-17 Juno Therapeutics, Inc. Process for producing a composition of engineered T cells
WO2019118937A1 (en) 2017-12-15 2019-06-20 Juno Therapeutics, Inc. Anti-cct5 binding molecules and methods of use thereof
US12006356B2 (en) 2017-12-15 2024-06-11 Juno Therapeutics, Inc. Anti-CCT5 binding molecules and chimeric antigen receptors comprising the same
CN112074534A (zh) * 2017-12-22 2020-12-11 阿尔麦克探索有限公司 双特异性抗原结合分子
WO2019129220A1 (en) * 2017-12-28 2019-07-04 Nanjing Legend Biotech Co., Ltd. Multispecific chimeric receptors comprising nkg2d domain and methods of use thereof
US12491153B2 (en) 2018-01-03 2025-12-09 Qu Biologics Inc. Innate targeting of adoptive cellular therapies
US11919937B2 (en) 2018-01-09 2024-03-05 Board Of Regents, The University Of Texas System T cell receptors for immunotherapy
AU2019206573B2 (en) * 2018-01-10 2024-06-06 The General Hospital Corporation Immune cells expressing a chimeric antigen receptor
EP3737688A4 (en) * 2018-01-10 2021-11-03 The General Hospital Corporation IMMUNE CELLS EXPRESSING A CHEMICAL ANTIGENIC RECEPTOR
CN108285486A (zh) * 2018-01-15 2018-07-17 浙江阿思科力生物科技有限公司 以cd20为靶点的特异性抗体、car-nk细胞及其制备和应用
US12269862B2 (en) 2018-01-22 2025-04-08 Endocyte, Inc. Methods of use for CAR T cells
US11779602B2 (en) 2018-01-22 2023-10-10 Endocyte, Inc. Methods of use for CAR T cells
KR20190092285A (ko) * 2018-01-29 2019-08-07 (주)에스엠티바이오 췌장 또는 담관계암 치료를 위한 키메라 항원 수용체
KR102115236B1 (ko) * 2018-01-29 2020-05-27 (주)에스엠티바이오 췌장 또는 담관계암 치료를 위한 키메라 항원 수용체
WO2019152743A1 (en) 2018-01-31 2019-08-08 Celgene Corporation Combination therapy using adoptive cell therapy and checkpoint inhibitor
US11535903B2 (en) 2018-01-31 2022-12-27 Juno Therapeutics, Inc. Methods and reagents for assessing the presence or absence of replication competent virus
US12264371B2 (en) 2018-01-31 2025-04-01 Juno Therapeutics, Inc. Methods and reagents for assessing the presence or absence of replication competent virus
WO2019152747A1 (en) 2018-01-31 2019-08-08 Juno Therapeutics, Inc. Methods and reagents for assessing the presence or absence of replication competent virus
CN108219004A (zh) * 2018-02-08 2018-06-29 吉林省拓华生物科技有限公司 双特异嵌合抗原受体修饰的t细胞、其制备方法及用途
US12240870B2 (en) 2018-02-23 2025-03-04 Purdue Research Foundation Sequencing method for CAR T cell therapy
WO2019170845A1 (en) 2018-03-09 2019-09-12 Ospedale San Raffaele S.R.L. Il-1 antagonist and toxicity induced by cell therapy
CN108251392A (zh) * 2018-03-30 2018-07-06 广东溢多利生物科技股份有限公司 提高比活和热稳定性的葡萄糖氧化酶突变体及其编码基因和应用
WO2019195486A1 (en) 2018-04-05 2019-10-10 Juno Therapeutics, Inc. T cell receptors and engineered cells expressing same
WO2019195492A1 (en) 2018-04-05 2019-10-10 Juno Therapeutics, Inc. Methods of producing cells expressing a recombinant receptor and related compositions
US11471489B2 (en) 2018-04-05 2022-10-18 Juno Therapeutics, Inc. T cell receptors and engineered cells expressing same
WO2019195586A1 (en) 2018-04-06 2019-10-10 The Regents Of The University Of California Methods of treating egfrviii expressing glioblastomas
WO2019195596A1 (en) 2018-04-06 2019-10-10 The Regents Of The University Of California Methods of treating glioblastomas
US12150960B2 (en) * 2018-04-17 2024-11-26 Innovative Cellular Therapeutics Holdings, Ltd. Modified cell expansion and uses thereof
US20210077532A1 (en) * 2018-04-17 2021-03-18 Innovative Cellular Therapeutics CO., LTD. Modified Cell Expansion and Uses Thereof
US11987804B2 (en) 2018-04-27 2024-05-21 Seattle Children's Hospital Rapamycin resistant cells
WO2019210153A1 (en) 2018-04-27 2019-10-31 Novartis Ag Car t cell therapies with enhanced efficacy
US12595492B2 (en) 2018-04-27 2026-04-07 Seattle Children's Hospital Rapamycin resistant cells
WO2019213282A1 (en) 2018-05-01 2019-11-07 Novartis Ag Biomarkers for evaluating car-t cells to predict clinical outcome
WO2019213184A1 (en) 2018-05-03 2019-11-07 Juno Therapeutics, Inc. Combination therapy of a chimeric antigen receptor (car) t cell therapy and a kinase inhibitor
WO2019227003A1 (en) 2018-05-25 2019-11-28 Novartis Ag Combination therapy with chimeric antigen receptor (car) therapies
WO2019237035A1 (en) 2018-06-08 2019-12-12 Intellia Therapeutics, Inc. Compositions and methods for immunooncology
US11939389B2 (en) 2018-06-13 2024-03-26 Novartis Ag BCMA chimeric antigen receptors and uses thereof
US11952428B2 (en) 2018-06-13 2024-04-09 Novartis Ag BCMA chimeric antigen receptors and uses thereof
WO2020012337A1 (en) 2018-07-10 2020-01-16 Novartis Ag 3-(5-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and their use in the treatment of i karos family zinc finger 2 (ikzf2)-dependent diseases
TWI841576B (zh) * 2018-07-13 2024-05-11 大陸商南京傳奇生物科技有限公司 用於治療傳染病之共受體系統
EP3820888A4 (en) * 2018-07-13 2022-04-27 Nanjing Legend Biotech Co., Ltd. CO-RECEPTOR SYSTEMS FOR THE TREATMENT OF INFECTIOUS DISEASES
US20210275589A1 (en) * 2018-07-13 2021-09-09 Nanjing Legend Biotech Co. Ltd. Co-receptor systems for treating infectious diseases
WO2020011247A1 (en) 2018-07-13 2020-01-16 Nanjing Legend Biotech Co., Ltd. Co-receptor systems for treating infectious diseases
CN112334479A (zh) * 2018-07-13 2021-02-05 南京传奇生物科技有限公司 用于治疗感染性疾病的共受体系统
US11406667B2 (en) 2018-07-17 2022-08-09 Triumvira Immunologies USA, Inc. T cell-antigen coupler with various construct optimizations
US11878035B2 (en) 2018-07-17 2024-01-23 Triumvira Immunologics Usa, Inc. T cell-antigen coupler with various construct optimizations
US11110123B2 (en) 2018-07-17 2021-09-07 Triumvira Immunologics Usa, Inc. T cell-antigen coupler with various construct optimizations
US11111298B2 (en) 2018-07-17 2021-09-07 Mcmaster University T cell-antigen coupler with various construct optimizations
US10640562B2 (en) 2018-07-17 2020-05-05 Mcmaster University T cell-antigen coupler with various construct optimizations
US11976117B2 (en) 2018-07-17 2024-05-07 Mcmaster University T cell-antigen coupler with various construct optimizations
WO2020033927A2 (en) 2018-08-09 2020-02-13 Juno Therapeutics, Inc. Processes for generating engineered cells and compositions thereof
WO2020033916A1 (en) 2018-08-09 2020-02-13 Juno Therapeutics, Inc. Methods for assessing integrated nucleic acids
US12516099B2 (en) 2018-08-09 2026-01-06 Juno Therapeutics, Inc. Processes for generating engineered cells and compositions thereof
US12240915B2 (en) 2018-08-30 2025-03-04 Innovative Cellular Therapeutics Holdings, Ltd. Chimeric antigen receptor cells for treating solid tumor
WO2020056047A1 (en) 2018-09-11 2020-03-19 Juno Therapeutics, Inc. Methods for mass spectrometry analysis of engineered cell compositions
US12366580B2 (en) 2018-09-11 2025-07-22 Juno Therapeutics, Inc. Methods for mass spectrometry analysis of engineered cell compositions
CN109293781A (zh) * 2018-09-12 2019-02-01 中国人民解放军总医院 嵌合抗原受体及其基因和重组表达载体、cd19-cd20双靶向性的t细胞及其应用
US12522660B2 (en) 2018-10-31 2026-01-13 C3S2 Gmbh Methods for selection and stimulation of cells and apparatus for same
WO2020089343A1 (en) 2018-10-31 2020-05-07 Juno Therapeutics Gmbh Methods for selection and stimulation of cells and apparatus for same
US12473345B2 (en) 2018-11-01 2025-11-18 Juno Therapeutics, Inc. Methods for treatment using chimeric antigen receptors specific for B-cell maturation antigen
WO2020092848A2 (en) 2018-11-01 2020-05-07 Juno Therapeutics, Inc. Methods for treatment using chimeric antigen receptors specific for b-cell maturation antigen
WO2020097132A1 (en) 2018-11-06 2020-05-14 Juno Therapeutics, Inc. Process for producing genetically engineered t cells
WO2020097403A1 (en) 2018-11-08 2020-05-14 Juno Therapeutics, Inc. Methods and combinations for treatment and t cell modulation
US12263190B2 (en) 2018-11-08 2025-04-01 Juno Therapeutics, Inc. Methods and combinations for treatment and T cell modulation
WO2020102770A1 (en) 2018-11-16 2020-05-22 Juno Therapeutics, Inc. Methods of dosing engineered t cells for the treatment of b cell malignancies
WO2020106621A1 (en) 2018-11-19 2020-05-28 Board Of Regents, The University Of Texas System A modular, polycistronic vector for car and tcr transduction
WO2020113029A2 (en) 2018-11-28 2020-06-04 Board Of Regents, The University Of Texas System Multiplex genome editing of immune cells to enhance functionality and resistance to suppressive environment
WO2020112493A1 (en) 2018-11-29 2020-06-04 Board Of Regents, The University Of Texas System Methods for ex vivo expansion of natural killer cells and use thereof
EP4471129A2 (en) 2018-11-29 2024-12-04 Board of Regents, The University of Texas System Methods for ex vivo expansion of natural killer cells and use thereof
WO2020113194A2 (en) 2018-11-30 2020-06-04 Juno Therapeutics, Inc. Methods for treatment using adoptive cell therapy
EP4427810A2 (en) 2018-11-30 2024-09-11 Juno Therapeutics, Inc. Methods for treatment using adoptive cell therapy
US12577311B2 (en) 2018-11-30 2026-03-17 Dana-Farber Cancer Institute, Inc. Chimeric antigen receptor factories and methods of use thereof
EP4393547A2 (en) 2018-11-30 2024-07-03 Juno Therapeutics, Inc. Methods for dosing and treatment of b cell malignancies in adoptive cell therapy
WO2020113188A2 (en) 2018-11-30 2020-06-04 Juno Therapeutics, Inc. Methods for dosing and treatment of b cell malignancies in adoptive cell therapy
EP3887509A4 (en) * 2018-11-30 2022-08-31 Dana-Farber Cancer Institute, Inc. CHIMERA ANTIGEN RECEPTOR AND METHODS OF USING THE SAME
US11793834B2 (en) 2018-12-12 2023-10-24 Kite Pharma, Inc. Chimeric antigen and T cell receptors and methods of use
US12583923B2 (en) 2018-12-12 2026-03-24 Kite Pharma, Inc. Chimeric antigen and T cell receptors and methods of use
TWI848225B (zh) * 2018-12-12 2024-07-11 美商凱特製藥公司 嵌合抗原及t細胞受體以及使用方法
TWI902626B (zh) * 2018-12-12 2025-10-21 美商凱特製藥公司 嵌合抗原及t細胞受體以及使用方法
TWI878150B (zh) * 2018-12-12 2025-03-21 美商凱特製藥公司 嵌合抗原及t細胞受體以及使用方法
WO2020128972A1 (en) 2018-12-20 2020-06-25 Novartis Ag Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives
EP4707385A2 (en) 2019-01-24 2026-03-11 Valorisation-HSJ, Limited Partnership Cell-specific transcriptional regulatory sequences and uses thereof
WO2020160050A1 (en) 2019-01-29 2020-08-06 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for receptor tyrosine kinase like orphan receptor 1 (ror1)
US12268741B2 (en) 2019-01-29 2025-04-08 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for receptor tyrosine kinase like orphan receptor 1 (ROR1)
EP3920952A4 (en) * 2019-02-08 2023-01-25 Seattle Children's Hospital (DBA Seattle Children's Research Institute) CHIMERIC CYTOKINE RECEPTORS
US11667715B2 (en) 2019-02-15 2023-06-06 University Of Southern California Lym-1 and Lym-2 antibody compositions and improved car constructs
WO2020165833A1 (en) 2019-02-15 2020-08-20 Novartis Ag 3-(1-oxo-5-(piperidin-4-yl)isoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2020165834A1 (en) 2019-02-15 2020-08-20 Novartis Ag Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
US20220145325A1 (en) * 2019-03-08 2022-05-12 Autolus Limited Compositions and methods comprising engineered chimeric antigen receptor and modulator of car
US12269860B2 (en) 2019-03-08 2025-04-08 Autolus Limited Compositions and methods comprising engineered chimeric antigen receptor and modulator of CAR
WO2020219742A1 (en) 2019-04-24 2020-10-29 Novartis Ag Compositions and methods for selective protein degradation
US12435120B2 (en) 2019-05-01 2025-10-07 Juno Therapeutics, Inc. Cells expressing a chimeric receptor from a modified CD247 locus, related polynucleotides and methods
WO2020223571A1 (en) 2019-05-01 2020-11-05 Juno Therapeutics, Inc. Cells expressing a chimeric receptor from a modified cd247 locus, related polynucleotides and methods
WO2020223535A1 (en) 2019-05-01 2020-11-05 Juno Therapeutics, Inc. Cells expressing a recombinant receptor from a modified tgfbr2 locus, related polynucleotides and methods
WO2020228825A1 (en) * 2019-05-16 2020-11-19 Nanjing Legend Biotech Co., Ltd. Engineered immune cells comprsing a recognition molecule
WO2020247832A1 (en) 2019-06-07 2020-12-10 Juno Therapeutics, Inc. Automated t cell culture
WO2020252218A1 (en) 2019-06-12 2020-12-17 Juno Therapeutics, Inc. Combination therapy of a cell-mediated cytotoxic therapy and an inhibitor of a prosurvival bcl2 family protein
US20220306719A1 (en) * 2019-06-19 2022-09-29 Julius-Maximilians-Universität Würzburg Ultramodular igg3-based spacer domain and multi-function site for implementation in chimeric antigen receptor design
WO2021013950A1 (en) 2019-07-23 2021-01-28 Mnemo Therapeutics Immune cells defective for suv39h1
WO2021035194A1 (en) 2019-08-22 2021-02-25 Juno Therapeutics, Inc. Combination therapy of a t cell therapy and an enhancer of zeste homolog 2 (ezh2) inhibitor and related methods
US12444491B2 (en) 2019-08-30 2025-10-14 Juno Therapeutics, Inc. Machine learning methods for classifying cells
WO2021041994A2 (en) 2019-08-30 2021-03-04 Juno Therapeutics, Inc. Machine learning methods for classifying cells
US12152077B1 (en) 2019-09-02 2024-11-26 Institut Curie Immunotherapy targeting tumor neoantigenic peptides
WO2021043804A1 (en) 2019-09-02 2021-03-11 Institut Curie Immunotherapy targeting tumor neoantigenic peptides
US12551560B2 (en) 2019-09-09 2026-02-17 Scribe Therapeutics Inc. Compositions and methods for use in immunotherapy
WO2021050601A1 (en) 2019-09-09 2021-03-18 Scribe Therapeutics Inc. Compositions and methods for use in immunotherapy
WO2021078910A1 (en) 2019-10-22 2021-04-29 Institut Curie Immunotherapy targeting tumor neoantigenic peptides
WO2021084050A1 (en) 2019-10-30 2021-05-06 Juno Therapeutics Gmbh Cell selection and/or stimulation devices and methods of use
WO2021092498A1 (en) 2019-11-07 2021-05-14 Juno Therapeutics, Inc. Combination of a t cell therapy and (s)-3-[4-(4-morpholin-4 ylmethyl-benzyloxy)-l-oxo-l,3-dihydro-isoindol-2-yl]- piperidine-2,6-dione
US11975026B2 (en) 2019-11-26 2024-05-07 Novartis Ag CD19 and CD22 chimeric antigen receptors and uses thereof
US12344651B2 (en) 2019-11-26 2025-07-01 Novartis Ag CD19 and CD22 chimeric antigen receptors and uses thereof
US12570749B2 (en) 2019-12-06 2026-03-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to GPRC5D-targeted binding domains and related compositions and methods
WO2021113780A1 (en) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to gprc5d-targeted binding domains and related compositions and methods
WO2021113776A1 (en) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to bcma-targeted binding domains and related compositions and methods
WO2021113770A1 (en) 2019-12-06 2021-06-10 Juno Therapeutics, Inc. Methods related to toxicity and response associated with cell therapy for treating b cell malignancies
WO2021123996A1 (en) 2019-12-20 2021-06-24 Novartis Ag Uses of anti-tgf-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases
JP2020099326A (ja) * 2019-12-27 2020-07-02 カースゲン セラピューティクス リミテッドＣａｒｓｇｅｎ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ キメラ抗原受容体タンパク質をコードする核酸およびキメラ抗原受容体タンパク質を発現するｔリンパ球
JP7088902B2 (ja) 2019-12-27 2022-06-21 クレージュ メディカル カンパニー，リミテッド キメラ抗原受容体タンパク質をコードする核酸およびキメラ抗原受容体タンパク質を発現するｔリンパ球
WO2021146487A2 (en) 2020-01-14 2021-07-22 Synthekine, Inc. Il2 orthologs and methods of use
WO2021151008A1 (en) 2020-01-24 2021-07-29 Juno Therapuetics, Inc. Methods for dosing and treatment of follicular lymphoma and marginal zone lymphoma in adoptive cell therapy
WO2021154887A1 (en) 2020-01-28 2021-08-05 Juno Therapeutics, Inc. Methods for t cell transduction
WO2021163391A1 (en) 2020-02-12 2021-08-19 Juno Therapeutics, Inc. Cd19-directed chimeric antigen receptor t cell compositions and methods and uses thereof
WO2021163389A1 (en) 2020-02-12 2021-08-19 Juno Therapeutics, Inc. Bcma-directed chimeric antigen receptor t cell compositions and methods and uses thereof
WO2021167908A1 (en) 2020-02-17 2021-08-26 Board Of Regents, The University Of Texas System Methods for expansion of tumor infiltrating lymphocytes and use thereof
US12076343B2 (en) 2020-02-19 2024-09-03 Innovative Cellular Therapeutics Holdings, Ltd. Engineered safety in cell therapy
WO2021173995A2 (en) 2020-02-27 2021-09-02 Novartis Ag Methods of making chimeric antigen receptor-expressing cells
US12448432B2 (en) 2020-03-17 2025-10-21 AbelZeta Inc. Combined chimeric antigen receptor targeting CD19 and CD20 and application thereof
US20210309717A1 (en) * 2020-03-20 2021-10-07 Lyell Immunopharma, Inc. Novel Recombinant Cell Surface Markers
US12054531B2 (en) * 2020-03-20 2024-08-06 Lyell Immunopharma, Inc. Recombinant cell surface markers
WO2021207689A2 (en) 2020-04-10 2021-10-14 Juno Therapeutics, Inc. Methods and uses related to cell therapy engineered with a chimeric antigen receptor targeting b-cell maturation antigen
WO2021228999A1 (en) 2020-05-12 2021-11-18 Institut Curie Neoantigenic epitopes associated with sf3b1 mutations
WO2021231657A1 (en) 2020-05-13 2021-11-18 Juno Therapeutics, Inc. Methods of identifying features associated with clinical response and uses thereof
WO2021231661A2 (en) 2020-05-13 2021-11-18 Juno Therapeutics, Inc. Process for producing donor-batched cells expressing a recombinant receptor
WO2021237068A2 (en) 2020-05-21 2021-11-25 Board Of Regents, The University Of Texas System T cell receptors with vgll1 specificity and uses thereof
US12043654B2 (en) 2020-06-02 2024-07-23 Innovative Cellular Therapeutics Holdings, Ltd. Anti-GCC antibody and CAR thereof for treating digestive system cancer
WO2021252920A1 (en) 2020-06-11 2021-12-16 Novartis Ag Zbtb32 inhibitors and uses thereof
WO2021260528A1 (en) 2020-06-23 2021-12-30 Novartis Ag Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives
WO2021260186A1 (en) 2020-06-26 2021-12-30 Juno Therapeutics Gmbh Engineered t cells conditionally expressing a recombinant receptor, related polynucleotides and methods
WO2022023576A1 (en) 2020-07-30 2022-02-03 Institut Curie Immune cells defective for socs1
WO2022029573A1 (en) 2020-08-03 2022-02-10 Novartis Ag Heteroaryl substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
WO2022029660A1 (en) 2020-08-05 2022-02-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to ror1-targeted binding domains and related compositions and methods
US11667723B2 (en) 2020-08-17 2023-06-06 Utc Therapeutics (Shanghai) Co., Ltd. Lymphocytes-antigen presenting cells co-stimulators and uses thereof
EP4200340A1 (en) 2020-08-21 2023-06-28 12343096 Canada Inc. Modular assembly receptors and uses thereof
US12024559B2 (en) 2020-10-23 2024-07-02 Asher Biotherapeutics, Inc. Fusions with CD8 antigen binding molecules for modulating immune cell function
EP4240831A4 (en) * 2020-11-04 2025-03-26 Fate Therapeutics, Inc. Engineered ipsc and persistent immune effector cells
WO2022104109A1 (en) 2020-11-13 2022-05-19 Catamaran Bio, Inc. Genetically modified natural killer cells and methods of use thereof
WO2022133030A1 (en) 2020-12-16 2022-06-23 Juno Therapeutics, Inc. Combination therapy of a cell therapy and a bcl2 inhibitor
US11883432B2 (en) 2020-12-18 2024-01-30 Century Therapeutics, Inc. Chimeric antigen receptor system with adaptable receptor specificity
WO2022150731A1 (en) 2021-01-11 2022-07-14 Sana Biotechnology, Inc. Use of cd8-targeted viral vectors
WO2022156786A1 (zh) * 2021-01-22 2022-07-28 南京助天中科科技发展有限公司 一种嵌合抗原受体改造的nk细胞及其制备方法与应用
WO2022166665A1 (zh) * 2021-02-08 2022-08-11 浙江大学 一种以内源性蛋白质分子替代单结构域抗体的嵌合抗原受体
US12144827B2 (en) 2021-02-25 2024-11-19 Lyell Immunopharma, Inc. ROR1 targeting chimeric antigen receptor
WO2022187406A1 (en) 2021-03-03 2022-09-09 Juno Therapeutics, Inc. Combination of a t cell therapy and a dgk inhibitor
WO2022189626A2 (en) 2021-03-11 2022-09-15 Mnemo Therapeutics Tumor neoantigenic peptides
WO2022189620A1 (en) 2021-03-11 2022-09-15 Institut Curie Transmembrane neoantigenic peptides
WO2022189639A1 (en) 2021-03-11 2022-09-15 Mnemo Therapeutics Tumor neoantigenic peptides and uses thereof
WO2022204070A1 (en) 2021-03-22 2022-09-29 Juno Therapeutics, Inc. Methods of determining potency of a therapeutic cell composition
WO2022204071A1 (en) 2021-03-22 2022-09-29 Juno Therapeutics, Inc. Method to assess potency of viral vector particles
WO2022212384A1 (en) 2021-03-29 2022-10-06 Juno Therapeutics, Inc. Combination of a car t cell therapy and an immunomodulatory compound for treatment of lymphoma
WO2022212400A1 (en) 2021-03-29 2022-10-06 Juno Therapeutics, Inc. Methods for dosing and treatment with a combination of a checkpoint inhibitor therapy and a car t cell therapy
WO2022215011A1 (en) 2021-04-07 2022-10-13 Novartis Ag USES OF ANTI-TGFβ ANTIBODIES AND OTHER THERAPEUTIC AGENTS FOR THE TREATMENT OF PROLIFERATIVE DISEASES
EP4326293A1 (en) 2021-04-22 2024-02-28 Baylor College of Medicine Methods of engineering immune cells having reduced fratricidal activity
WO2022229853A1 (en) 2021-04-27 2022-11-03 Novartis Ag Viral vector production system
WO2022234009A2 (en) 2021-05-06 2022-11-10 Juno Therapeutics Gmbh Methods for stimulating and transducing t cells
US12016923B2 (en) 2021-06-01 2024-06-25 Triumvira Immunologics Usa, Inc. Claudin 18.2 T cell-antigen couplers and uses thereof
US11453723B1 (en) 2021-06-25 2022-09-27 Mcmaster University BCMA T cell-antigen couplers and uses thereof
WO2023014922A1 (en) 2021-08-04 2023-02-09 The Regents Of The University Of Colorado, A Body Corporate Lat activating chimeric antigen receptor t cells and methods of use thereof
WO2023015217A1 (en) 2021-08-04 2023-02-09 Sana Biotechnology, Inc. Use of cd4-targeted viral vectors
WO2023017544A1 (en) * 2021-08-12 2023-02-16 Cellogen Therapeutics Pvt. Ltd. Chimeric antigen receptors (car) for b cell malignancies
WO2023037125A1 (en) 2021-09-10 2023-03-16 Ucl Business Ltd Binding domain
WO2023105000A1 (en) 2021-12-09 2023-06-15 Zygosity Limited Vector
WO2023115039A2 (en) 2021-12-17 2023-06-22 Sana Biotechnology, Inc. Modified paramyxoviridae fusion glycoproteins
WO2023115041A1 (en) 2021-12-17 2023-06-22 Sana Biotechnology, Inc. Modified paramyxoviridae attachment glycoproteins
WO2023126458A1 (en) 2021-12-28 2023-07-06 Mnemo Therapeutics Immune cells with inactivated suv39h1 and modified tcr
WO2023139269A1 (en) 2022-01-21 2023-07-27 Mnemo Therapeutics Modulation of suv39h1 expression by rnas
WO2023147515A1 (en) 2022-01-28 2023-08-03 Juno Therapeutics, Inc. Methods of manufacturing cellular compositions
WO2023150518A1 (en) 2022-02-01 2023-08-10 Sana Biotechnology, Inc. Cd3-targeted lentiviral vectors and uses thereof
WO2023178348A1 (en) 2022-03-18 2023-09-21 The Regents Of The University Of Colorado, A Body Corporate Genetically engineered t-cell co-receptors and methods of use thereof
WO2023180552A1 (en) 2022-03-24 2023-09-28 Institut Curie Immunotherapy targeting tumor transposable element derived neoantigenic peptides in glioblastoma
WO2023193015A1 (en) 2022-04-01 2023-10-05 Sana Biotechnology, Inc. Cytokine receptor agonist and viral vector combination therapies
WO2023196921A1 (en) 2022-04-06 2023-10-12 The Regents Of The University Of Colorado, A Body Corporate Granzyme expressing t cells and methods of use
WO2023196933A1 (en) 2022-04-06 2023-10-12 The Regents Of The University Of Colorado, A Body Corporate Chimeric antigen receptor t cells and methods of use thereof
WO2023211972A1 (en) 2022-04-28 2023-11-02 Medical University Of South Carolina Chimeric antigen receptor modified regulatory t cells for treating cancer
WO2023213969A1 (en) 2022-05-05 2023-11-09 Juno Therapeutics Gmbh Viral-binding protein and related reagents, articles, and methods of use
WO2023214325A1 (en) 2022-05-05 2023-11-09 Novartis Ag Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors
WO2023220655A1 (en) 2022-05-11 2023-11-16 Celgene Corporation Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy
EP4279085A1 (en) 2022-05-20 2023-11-22 Mnemo Therapeutics Compositions and methods for treating a refractory or relapsed cancer or a chronic infectious disease
WO2023222928A2 (en) 2022-05-20 2023-11-23 Mnemo Therapeutics Compositions and methods for treating a refractory or relapsed cancer or a chronic infectious disease
WO2023230581A1 (en) 2022-05-25 2023-11-30 Celgene Corporation Methods of manufacturing t cell therapies
WO2023250400A1 (en) 2022-06-22 2023-12-28 Juno Therapeutics, Inc. Treatment methods for second line therapy of cd19-targeted car t cells
WO2024006960A1 (en) 2022-06-29 2024-01-04 Juno Therapeutics, Inc. Lipid nanoparticles for delivery of nucleic acids
WO2024044779A2 (en) 2022-08-26 2024-02-29 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for delta-like ligand 3 (dll3)
WO2024054944A1 (en) 2022-09-08 2024-03-14 Juno Therapeutics, Inc. Combination of a t cell therapy and continuous or intermittent dgk inhibitor dosing
WO2024062138A1 (en) 2022-09-23 2024-03-28 Mnemo Therapeutics Immune cells comprising a modified suv39h1 gene
WO2024081820A1 (en) 2022-10-13 2024-04-18 Sana Biotechnology, Inc. Viral particles targeting hematopoietic stem cells
WO2024089639A1 (en) 2022-10-26 2024-05-02 Novartis Ag Lentiviral formulations
WO2024100604A1 (en) 2022-11-09 2024-05-16 Juno Therapeutics Gmbh Methods for manufacturing engineered immune cells
WO2024124132A1 (en) 2022-12-09 2024-06-13 Juno Therapeutics, Inc. Machine learning methods for predicting cell phenotype using holographic imaging
WO2024161021A1 (en) 2023-02-03 2024-08-08 Juno Therapeutics Gmbh Methods for non-viral manufacturing of engineered immune cells
WO2024182516A1 (en) 2023-02-28 2024-09-06 Juno Therapeutics, Inc. Cell therapy for treating systemic autoimmune diseases
US12458667B2 (en) 2023-03-31 2025-11-04 AbelZeta Inc. Bispecific chimeric antigen receptors targeting CD20 and BCMA
US12311022B2 (en) 2023-03-31 2025-05-27 AbelZeta Inc. Bispecific chimeric antigen receptors targeting CD20 and BCMA
WO2024220560A1 (en) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Engineered protein g fusogens and related lipid particles and methods thereof
WO2024220574A1 (en) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Universal protein g fusogens and adapter systems thereof and related lipid particles and uses
WO2024220598A2 (en) 2023-04-18 2024-10-24 Sana Biotechnology, Inc. Lentiviral vectors with two or more genomes
WO2024220588A1 (en) 2023-04-18 2024-10-24 Juno Therapeutics, Inc. Cytotoxicity assay for assessing potency of therapeutic cell compositions
WO2024226858A1 (en) 2023-04-26 2024-10-31 Juno Therapeutics, Inc. Methods for viral vector manufacturing
WO2024243365A2 (en) 2023-05-23 2024-11-28 Juno Therapeutics, Inc. Activation markers of t cells and method for assessing t cell activation
WO2024243441A1 (en) 2023-05-24 2024-11-28 Kumquat Biosciences Inc. Heterocyclic compounds and uses thereof
WO2025054202A1 (en) 2023-09-05 2025-03-13 Sana Biotechnology, Inc. Method of screening a sample comprising a transgene with a unique barcode
WO2025052001A1 (en) 2023-09-07 2025-03-13 Mnemo Therapeutics Methods and compositions for improving immune response
EP4520334A1 (en) 2023-09-07 2025-03-12 Mnemo Therapeutics Methods and compositions for improving immune response
WO2025082603A1 (en) 2023-10-18 2025-04-24 Institut Curie Engineered immune cells overexpressing cd74 molecule
WO2025096975A1 (en) 2023-11-02 2025-05-08 The Regents Of The University Of Colorado, A Body Corporate Compositions and methods of enhancing immune cell therapies by runx2 modulation
WO2025147545A1 (en) 2024-01-03 2025-07-10 Juno Therapeutics, Inc. Lipid nanoparticles for delivery of nucleic acids and related methods and uses
WO2025151838A1 (en) 2024-01-12 2025-07-17 Sana Biotechnology, Inc. Safety switches to control in vitro and in vivo proliferation of cell therapy products
WO2025163107A1 (en) 2024-02-01 2025-08-07 Institut Gustave Roussy Immune cells defective for znf217 and uses thereof
WO2025176853A1 (en) 2024-02-22 2025-08-28 Miltenyi Biotec B.V. & Co. KG Cd4- or cd8-targeted retroviral vector particles for generation of cells expressing a bispecific chimeric antigen receptor
WO2025184421A1 (en) 2024-02-28 2025-09-04 Juno Therapeutics, Inc. Chimeric antigen receptors and antibodies specific for delta-like ligand 3 (dll3) and related methods
WO2025231185A1 (en) 2024-05-01 2025-11-06 Legend Biotech Ireland Limited Viral glycoprotein variants and uses thereof
WO2025235851A1 (en) 2024-05-10 2025-11-13 Juno Therapeutics, Inc. Genetically engineered t cells expressing a cd19 chimeric antigen receptor (car) and uses thereof for allogeneic cell therapy
NL2037811B1 (en) 2024-05-29 2025-12-12 Univ Oslo Treatment for Cancer
WO2025250011A1 (en) 2024-05-29 2025-12-04 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Treatment for cancer
WO2025259108A1 (en) 2024-06-11 2025-12-18 Prinses Máxima Centrum Voor Kinderoncologie B.V. Brain organoid
NL2037929B1 (en) 2024-06-11 2026-01-12 Prinses Maxima Centrum Voor Kinderoncologie B V Brain Organoid
WO2026020055A2 (en) 2024-07-18 2026-01-22 Juno Therapeutics, Inc. Methods for assessing exosomes in a cell composition and related uses
WO2026025092A1 (en) 2024-07-26 2026-01-29 Juno Therapeutics, Inc. Synthetic promoters for t cell expression
WO2026062222A1 (en) 2024-09-20 2026-03-26 Institut Curie Novel protein isoforms and uses

Also Published As

Publication number Publication date
US10189903B2 (en) 2019-01-29
JP7836847B2 (ja) 2026-03-27
US12466885B2 (en) 2025-11-11
US11639387B2 (en) 2023-05-02
AU2017264982B2 (en) 2020-02-13
US10829556B2 (en) 2020-11-10
AU2017264982A1 (en) 2017-12-07
US9447194B2 (en) 2016-09-20
US20210309740A1 (en) 2021-10-07
CA2861491A1 (en) 2013-08-22
JP2015513394A (ja) 2015-05-14
AU2020203137A1 (en) 2020-06-04
AU2023248177A2 (en) 2023-11-23
US20170107285A1 (en) 2017-04-20
US20190119382A1 (en) 2019-04-25
EP3594245A1 (en) 2020-01-15
EP2814846B1 (en) 2020-01-08
US20230227551A1 (en) 2023-07-20
HK1205144A1 (en) 2015-12-11
JP2021121222A (ja) 2021-08-26
JP6850528B2 (ja) 2021-03-31
CA2861491C (en) 2020-08-25
AU2013221672A1 (en) 2014-08-07
AU2020203137B2 (en) 2023-07-13
EP2814846A4 (en) 2015-11-04
JP2019088330A (ja) 2019-06-13
JP2024083617A (ja) 2024-06-21
ES2774160T3 (es) 2020-07-17
US20150038684A1 (en) 2015-02-05
US20240400682A1 (en) 2024-12-05
AU2013221672B2 (en) 2017-11-09
AU2023248177A1 (en) 2023-11-02
US12091459B2 (en) 2024-09-17
EP2814846A1 (en) 2014-12-24

Similar Documents

Publication Publication Date Title
US12466885B2 (en) Bispecific chimeric antigen receptors and encoding polynucleotides, vectors and cells thereof
EP3313874B1 (en) Masking chimeric antigen receptor t cells for tumor-specific activation
AU2020232216A1 (en) Chimeric cytokine receptors bearing a PD-1 ectodomain
CN114085855A (zh) 通用嵌合抗原受体表达性免疫细胞及其制造方法和治疗用途
EP3645561B1 (en) Compositions and methods for adoptive cell therapy for cancer
TW202208415A (zh) Ｉｌ－１２裝甲的免疫細胞療法及其用途
US20220325241A1 (en) Immune effector cell for co-expressing chemokine receptor
CN117693528A (zh) 抗cll1抗体及其构建体
HK1205144B (en) Bispecific chimeric antigen receptors and therapeutic uses thereof
HK1247625A1 (en) Masking chimeric antigen receptor t cells for tumor-specific activation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13748596

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2861491

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2013748596

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 14376610

Country of ref document: US

ENP Entry into the national phase

Ref document number: 2013221672

Country of ref document: AU

Date of ref document: 20130213

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2014556818

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE