A device is provided for filling and emptying of an electroporation chamber. In particular, the device comprises a tubing set (10) having a main tube (11) with a first end (12) for connection to a cell suspension input bag (1) and a second end for connection to an electroporation chamber (3). A first branch tube from a first junction (16) with the main tube has at its other end a connection for an exogenous material input bag (2). A second junction between the first junction (16) and the connection to the electroporation chamber leads to a second branch tube (20) for connection to an output container (4). Further, one or more pumps are arranged to act upon the main tube, the first branch tube and the second branch tube respectively so as to displace fluid therein.
New engineered immune cells expressing two CARs directed against two different targets, polynucleotides for preparing said immune cells, pharmaceutical compositions comprising said immune cells, and the use of said immune cells in the treatment of cancers are provided herein.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
3.
ENHANCING EFFICACY AND SAFETY OF T-CELL-MEDIATED IMMUNOTHERAPY
This document relates to engineered immune cells comprising a tumor-CAR and a FAPscFv-cytokine fusion protein with differential expressions, their use in the treatment of tumors expressing FAP, as well as methods and materials for the preparation thereof.
The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.
The present invention provides methods for preparing expanded tumor infiltrating lymphocytes (TILs) having reduced expression of PD-1 and TIGIT using sequential electroporation of two TALEN systems targeting PD-1 and TIGIT. Such TILs find use in therapeutic treatment regimens for cancer patients.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/90 - Stable introduction of foreign DNA into chromosome
6.
TALE PROTEIN SCAFFOLDS INVOLVING FUSIONS OF MONOPARTITE AND BIPARTITE NLS
The present invention relates to the design of improved TALE protein fusions useful as sequence-specific genomic reagents, such as TALE-nucleases and TALE base editors, comprising series of nucleus localization signals (NLS), especially a fusion of at least two monopartite NLS, such as from C-myc (C-myc NLS) and/or from SV40 T antigen (SV40 T NLS), and at least one bi-partite NLS, such as from Nucleoplasmin (Nucleoplasmin NLS). The goal of these fusions is to produce safer TALE reagents to genetically modify genomes and/or its organisation in different types of cells for their potential use in gene therapy.
C12N 15/62 - DNA sequences coding for fusion proteins
C07K 14/46 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates
C07K 14/025 - Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present invention relates to methods using base editors for efficiently genetically engineer cells, especially primary hematopoietic stem cells (HSCs) and primary immune cells. In particular, the invention is directed to rules for designing highly active and specific TALE-base editors displaying improved on-target/off-target activity ratios useful to manufacture complex gene edited cells of therapeutic grade or to perform in-vivo gene therapy. The resulting TALE-base editors can be used alone or in combination with rare-cutting endonucleases in various gene therapy approaches.
A method for engineering less alloreactive immune cells, including T-cells that express chimeric antigen receptors (CARs), using a nucleotide sequence in form of an RNA encoding a anti-TCR CAR to achieve the transient expression of anti-TCR CAR at the cell surface. The transient expression of the anti-TCR CAR recognized by the alpha beta TCR on the cell surface unexpectedly enabled the a purification of the TCR-negative CAR expressing cells. The TCR-negative CAR expressing immune cells can be used in adoptive therapy to treat diseases associated with cell surface antigens, such as cancer with less side effects, in particular less GVHD.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 40/11 - T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cellsLymphokine-activated killer [LAK] cells
A61K 40/22 - Immunosuppressive or immunotolerising
The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of genetically modified TILs with reduced expression of CISH and optionally PD-1 as described herein.
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (France)
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (APHP) (France)
UNIVERSITE PARIS CITE (France)
FONDATION IMAGINE (France)
Inventor
Juillerat, Alexandre
Duchateau, Philippe
Valton, Julien
Boyne, Alex
Kracker, Sven
Cavazzana, Marina
Poggi, Lucie
Abstract
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to ex vivo gene therapy for the treatment of Activated PI3kinase Delta Syndrome type 1 (APDS1) related to PIK3CD gene. Particularly, the present invention pertains to the treatment of PIK3CD deficiency in hematopoietic stem cells (HSCs) and/or T-cells. The present invention provides means and methods for genetically modifying HSCs and/or T-cells involving gene editing reagents, such as TALE-nucleases, that specifically target an endogenous PIK3CD locus, at least in the PIK3CD allele comprising at least one APDS1-associated mutation, thereby allowing the restoration of the normal cellular phenotype. The present invention also provides engineered PIK3CD-edited HSCs and engineered PIK3CD-edited T-cells comprising at least one exogenous sequence comprising a nucleic acid sequence encoding a functional PI3Kδ protein which is integrated in said HSCs' or T-cells' genome into a PIK3CD locus, in a non-functional PIK3CD allele, resulting in the expression of a functional PI3Kδ polypeptide. The present invention further provides populations of cells comprising said engineered HSCs or T-cells, pharmaceutical compositions comprising said engineered cells or populations of cells, as well as their use in gene therapy for the treatment of APDS1.
This document relates to engineered immune cells comprising a FAP-CAR and a tumor-CAR with differential expressions, their use in the treatment of tumors expressing FAP, as well as methods and materials for the preparation thereof.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
13.
METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION
The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and/or class II major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and/or CIITA, or by using nucleic acid molecules which inhibit the expression of B2M and/or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component. In addition, expression of immunosuppressive polypeptide can be performed on those modified T-cells in order to prolong the survival of these modified T cells in host organism. Such modified T-cell is particularly suitable for allogeneic transplantations, especially because it reduces both the risk of rejection by the host's immune system and the risk of developing graft versus host disease. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer, infections and auto-immune diseases.
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Sickle Cell Disease. Described herewith are ex vivo methods for preparing a population of cells enriched in human HBB-gene-edited Hematopoietic Stem and Progenitor Cells (HSPCs) with enhanced engraftment capacity and therapeutic potential suitable for use in the treatment of sickle cell disease, means to carry out these methods, the population of HBB-gene edited HSPCs produced by these methods and the use thereof in the treatment of sickle cell disease.
The invention presents a device for homogenization and agitation of contents within a suspended cell culture bag. The device comprises a back plate and a compression bar positioned in parallel to the back plate with a variable gap. Attached to the compression bar are at least one push rod, allowing the adjustment of the gap width between a first and second width. When the cell culture bag is positioned between the back plate and compression bar, periodic variation of the gap width causes homogenization and agitation of the bag contents.
C12M 1/00 - Apparatus for enzymology or microbiology
B01F 31/55 - Mixers with shaking, oscillating, or vibrating mechanisms the materials to be mixed being contained in a flexible bag submitted to periodical deformation
C12M 3/06 - Tissue, human, animal or plant cell, or virus culture apparatus with filtration, ultrafiltration, inverse osmosis or dialysis means
C12M 1/42 - Apparatus for the treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic wave
16.
METHODS FOR NON-TRANSGENIC GENOME EDITING IN PLANTS
Materials and methods are provided for making plants (e.g., Triticum varieties) with increased levels of dietary fiber, such as by making TALE nuclease-induced mutations in alleles encoding starch branching enzyme IIa (SBEIIa) and starch branching enzyme IIb (SBEIIb).
The invention relates to methods of treatment of a solid tumor in a patient in need thereof, comprising administering to the patient: (i) an effective amount of engineered immune cells originating from a donor expressing at their cell surface a Chimeric Antigen Receptor (CAR) directed against Fibroblast Activation Protein (FAP), and (ii) an effective amount of an immunotherapy treatment that elicits an immune response in the patient.
The present invention provides composition kits and methods for treating cancer in a human by immunotherapy using successive doses of CAR-T cells with no or reduced anamnestic immune reaction in one individual (P).
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention relates to an engineered immune cell endowed with a new CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect said immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
21.
METHODS FOR IDENTIFYING TALE BASE EDITORS OFF-SITES
The present invention relates to methods using base editors for efficiently genetically engineer cells, especially primary hematopoietic stem cells (HSCs) and primary immune cells. In particular, the invention is directed to comprehensively investigate the specificity of TALE-base editors displaying improved on-target/off-target activity ratios useful to manufacture complex gene edited cells of therapeutic grade or to perform in-vivo gene therapy. The resulting TALE- base editors can be used alone or in combination with rare-cutting endonucleases in various gene therapy approaches.
A device is provided for delivering electrical signals to an electroporation chamber and for monitoring the quality of the delivered signals. Specifically, the device is of a modular construction comprising a main module and an audit module. The main module has control electronics with a signal generator configured to generate electrical pulses for electroporation and is electrically connected to the audit module. The audit module is configured to store calibration data and to measure with respect to time current and voltage passed from the main module and to pass such measurement data to the main module. The main module is configured to generate an error signal if the voltage and current measured by the audit module does not conform with expected values of voltage and current. The audit module is removably attached to the main module.
The invention relates to an inhibitory chimeric antigen receptor (N-CAR) comprising
an extracellular domain comprising an antigen binding domain,
a transmembrane domain and,
an intracellular domain
wherein the intracellular domain comprises an Immunoreceptor Tyrosine-based Switch Motif ITSM, wherein said ITSM is a sequence of amino acid TX1YX2X3X4, wherein
X1 is an amino acid
X2 is an amino acid
X3 is an amino acid and
X4 is V or I.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
25.
GENE THERAPY FOR THE TREATMENT OF SEVERE COMBINED IMMUNODEFICIENCY (SCID) RELATED TO RAG1
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Severe Combined Immunodeficiency (SCID) related to RAG1. Particularly, the present invention pertains to the treatment of RAG1 deficiency in long-term repopulating hematopoietic stem cells (HSCs). The present invention provides means and methods for genetically modifying HSCs involving gene editing reagents, such as TALE-nucleases, that specifically target a non-functional endogenous RAG1 gene, comprising at least one mutation causing Severe Combined Immunodeficiency (SCID), thereby allowing the restoration of the normal cellular phenotype. The present invention also provides engineered RAG1-edited HSCs comprising an exogenous sequence comprising a nucleic acid sequence encoding a functional RAG1 protein which is integrated in said HSCs' genome into a non-functional RAG1 endogenous locus, resulting in the expression of a functional RAG1 polypeptide. The present invention further provides populations of cells comprising said engineered HSCs, pharmaceutical compositions comprising said engineered HSCs or populations of cells, as well as their use in gene therapy for the treatment of Severe Combined Immunodeficiency (SCID) related to RAG1.
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Methods for developing engineered T-cells for immunotherapy that are both non-alloreactive and resistant to immunosuppresive drugs. The present invention relates to methods for modifying T-cells by inactivating both genes encoding target for an immunosuppressive agent and T-cell receptor, in particular genes encoding CD52 and TCR. This method involves the use of specific rare cutting endonucleases, in particular, TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection. of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
27.
GENE THERAPY FOR THE TREATMENT OF HYPER-IgE SYNDROME (HIES) BY TARGETED GENE INTEGRATION
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Hyper-lgE syndrome (HIES). In particular, the present invention provides means and methods for genetically modifying HSCs or T-cells involving gene editing reagents, such as TALE-nucleases, that specifically target an endogenous STATS gene comprising at least one mutation causing Hyper-lgE syndrome (HIES), thereby allowing the restoration of the normal cellular phenotype. The present invention also provides populations of engineered HSCs or T-cells which comprise cells comprising an exogenous polynucleotide sequence comprising at least a partial or complete sequence of a functional STATS gene, said exogenous polynucleotide sequence being integrated in an endogenous STATS gene comprising at least one mutation causing Hyper-lgE syndrome (HIES), resulting in the expression of a functional STATS polypeptide. The present invention further provides pharmaceutical compositions comprising the cell populations of the invention, and their use in gene therapy for the treatment of Hyper-lgE syndrome (HIES).
The present invention relates to chimeric antigen receptors (CAR). CARs are able to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties. In particular, the present invention relates to a Chimeric Antigen Recept—or in which extracellular ligand binding is a scFV derived from a CD19 monoclonal antibody, preferably 4G7. The present invention also relates to polynucleotides, vectors encoding said CAR and isolated cells expressing said CAR at their surface. The present invention also relates to methods for engineering immune cells expressing 4G7-CAR at their surface which confers a prolonged “activated” state on the transduced cell. The present invention is particularly useful for the treatment of B-cells lymphomas and leukemia.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
A device is provided for filling and emptying of an electroporation chamber. In particular, the device comprises a tubing set (10) having a main tube (11) with a first end (12) for connection to a cell suspension input bag (1) and a second end for connection to an electroporation chamber (3). A first branch tube from a first junction (16) with the main tube has at its other end a connection for an exogenous material input bag (2). A second junction between the first junction (16) and the connection to the electroporation chamber leads to a second branch tube (20) for connection to an output container (4). Further, one or more pumps are arranged to act upon the main tube, the first branch tube and the second branch tube respectively so as to displace fluid therein.
A polypeptide encoding a chimeric antigen receptor (CAR) comprising at least one extracellular binding domain that comprises a scFv formed by at least a VH chain and a VL chain specific to an antigen, wherein said extracellular binding domain comprises at least one mAb-specific epitope.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
G01N 15/01 - Investigating characteristics of particlesInvestigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
The present invention relates to genetically engineered immune cells expressing new anti-MUC1 chimeric antigen receptors and their use in the treatment of solid tumors, particularly suited for allogeneic cell immunotherapy.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/90 - Stable introduction of foreign DNA into chromosome
The present invention relates to an engineered immune cell endowed with CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
This document relates to methods of immunotherapy comprising administering CAR-T cells to a subject in need thereof, in particular a 2-dose regimen of CAR-T therapy, and materials and compositions to carry out such methods.
The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a CD33 monoclonal antibody, conferring specific immunity against CD33 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
This document relates to engineered immune cells comprising a tumor-CAR and a FAPscFv-cytokine fusion protein with differential expressions, their use in the treatment of tumors expressing FAP, as well as methods and materials for the preparation thereof.
The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.
The present invention provides methods for preparing expanded tumor infiltrating lymphocytes (TILs) having reduced expression of PD-1 and TIGIT using sequential electroporation of two TALEN systems targeting PD-1 and TIGIT. Such TILs find use in therapeutic treatment regimens for cancer patients.
The present invention provides methods for preparing expanded tumor infiltrating lymphocytes (TILs) having reduced expression of PD-1 and TIGIT using sequential electroporation of two TALEN systems targeting PD-1 and TIGIT. Such TILs find use in therapeutic treatment regimens for cancer patients.
Materials and methods for creating canola (e.g., Brassica napus) lines having oil with increased oleic acid content are provided herein. For example, a Brassica plant, plant part, or plant cell having an induced mutation in one or more FAD2 gene copies, oil produced from the plant, plant part, or plant cell has increased oleic acid content and decreased linolenic acid content as compared to oil produced from a corresponding wild type Brassica plant, plant part, or plant cell, wherein the mutation was induced by one or more rare cutting endonucleases targeted to the one or more FAD2 gene copies, and methods of making and using the Brassica plant, plant part or plant cell, are provided.
The present invention pertains to engineered T-cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered T-cells of the invention are characterized in that the expression of beta 2-microglobulin (B2M) and/or class II major histocompatibility complex transactivator (CIITA) is inhibited, e.g., by using rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding B2M and/or CIITA, or by using nucleic acid molecules which inhibit the expression of B2M and/or CIITA. In order to further render the T-cell non-alloreactive, at least one gene encoding a component of the T-cell receptor is inactivated, e.g., by using a rare-cutting endonucleases able to selectively inactivating by DNA cleavage the gene encoding said TCR component.
This document relates to engineered immune cells comprising a FAP-CAR and a tumor-CAR with differential expressions, their use in the treatment of tumors expressing FAP, as well as methods and materials for the preparation thereof.
This document relates to engineered immune cells comprising a FAP-CAR and a tumor-CAR with differential expressions, their use in the treatment of tumors expressing FAP, as well as methods and materials for the preparation thereof.
The invention provides aminoquinoline compounds as powerful enhancers of genetic recombination in living cells, especially to perform site-directed gene integration of exogenous DNA template by homologous recombination. In particular, disclosed are methods by which cells are treated with chloroquine and/or hydroxychloroquine prior to, or concomitantly with, the introduction of exogenous DNA templates, and optionally in presence of rare-cutting endonucleases, to obtain higher rates of gene integration or correction.
The present invention relates to methods using base editors for efficiently genetically engineer cells, especially primary hematopoietic stem cells (HSCs) and primary immune cells. In particular, the invention is directed to rules for designing highly active and specific TALE-base editors displaying improved on-target/off-target activity ratios useful to manufacture complex gene edited cells of therapeutic grade or to perform in-vivo gene therapy. The resulting TALE-base editors can be used alone or in combination with rare-cutting endonucleases in various gene therapy approaches.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
The present invention relates to methods using base editors for efficiently genetically engineer cells, especially primary hematopoietic stem cells (HSCs) and primary immune cells. In particular, the invention is directed to rules for designing highly active and specific TALE-base editors displaying improved on-target/off-target activity ratios useful to manufacture complex gene edited cells of therapeutic grade or to perform in-vivo gene therapy. The resulting TALE-base editors can be used alone or in combination with rare-cutting endonucleases in various gene therapy approaches.
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
50.
GENE THERAPY FOR THE TREATMENT OF ACTIVATED PI3KINASE DELTA SYNDROME TYPE 1 (APDS1)
INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE (France)
ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS (APHP) (France)
UNIVERSITÉ PARIS CITÉ (France)
FONDATION IMAGINE (France)
Inventor
Juillerat, Alexandre
Duchateau, Philippe
Valton, Julien
Boyne, Alex
Kracker, Sven
Cavazzana, Marina
Poggi, Lucie
Abstract
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to ex vivo gene therapy for the treatment of Activated PI3kinase Delta Syndrome type 1 (APDS1) related to PIK3CD gene. Particularly, the present invention pertains to the treatment of PIK3CD deficiency in hematopoietic stem cells (HSCs) and/or T-cells. The present invention provides means and methods for genetically modifying HSCs and/or T-cells involving gene editing reagents, such as TALE-nucleases, that specifically target an endogenous PIK3CD locus, at least in the PIK3CD allele comprising at least one APDS1-associated mutation, thereby allowing the restoration of the normal cellular phenotype. The present invention also provides engineered PIK3CD-edited HSCs and engineered PIK3CD-edited T-cells comprising at least one exogenous sequence comprising a nucleic acid sequence encoding a functional PI3Kδ protein which is integrated in said HSCs' or T-cells' genome into a PIK3CD locus, in a non-functional PIK3CD allele, resulting in the expression of a functional PI3Kδ polypeptide. The present invention further provides populations of cells comprising said engineered HSCs or T-cells, pharmaceutical compositions comprising said engineered cells or populations of cells, as well as their use in gene therapy for the treatment of APDS1.
Methods of developing genetically engineered immune cells for immunotherapy, which can be endowed with Chimeric Antigen Receptors targeting an antigen marker that is common to both the pathological cells and said immune cells (ex: CD38, CSI or CD70) by the fact that the genes encoding said markers are inactivated in said immune cells by a rare cutting endonuclease such as TALEN, Cas9 or argonaute.
The invention pertains to the field of adaptive cell immunotherapy. It aims at reducing the occurrence of translocations and cell deaths when several specific endonuclease reagents are used altogether to genetically modify primary immune cells at different genetic loci. The method of the invention allows to yield safer immune primary cells harboring several genetic modifications, such as triple or quadruple gene inactivated cells, from populations or sub-populations of cells originating from a single donor or patient, for their subsequent use in therapeutic treatments.
The present disclosure provides methods to genetically modify cells by insertion of an artificial exon (ArtEx) for delivery of therapeutic proteins in specific cell types and more particularly engineered cells for expression of a transgene into the brain of a patient.
The present invention concerns new engineered immune cells expressing two CARs directed against two different targets, polynucleotides for preparing said immune cells, pharmaceutical compositions comprising said immune cells, and the use of said immune cells in the treatment of cancers.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
55.
T-CELLS EXPRESSING IMMUNE CELL ENGAGERS IN ALLOGENIC SETTINGS
The invention relates to therapeutic compositions for allogeneic cellular therapy comprising TCR deficient T-cells, which are genetically engineered to express immune cell engagers, and methods related thereto.
The invention relates to a new potency assay for characterizing the quality and activity of an immune cell expressing a chimeric antigen receptor, the kit to carry out this assay and uses thereof.
The present disclosure provides methods for targeted insertion of an exogenous sequence at a genomic locus in a cell, wherein said insertion is induced by a sequence-specific endonuclease that has cleavage activity at said locus, at least 5 hours before the introduction into said cell of a DNA template comprising said exogenous sequence.
The present invention relates to methods for developing engineered T-cells for immunotherapy that are non-alloreactive. The present invention relates to methods for modifying T-cells by inactivating both genes encoding T-cell receptor and an immune checkpoint gene to unleash the potential of the immune response. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/63 - Introduction of foreign genetic material using vectorsVectorsUse of hosts thereforRegulation of expression
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
The present invention relates to the design of improved TALE protein fusions useful as sequence-specific genomic reagents, such as TALE-nucleases and TALE base editors, displaying higher on-target/off-target activity ratios. Its goal is to produce safer reagents to genetically modify the genomes of different types of cells, especially mammalian cells, in particular for their use in gene therapy.
COMBINATION COMPRISING ALLOGENEIC IMMUNE CELLS DEFICIENT FOR AN ANTIGEN PRESENT ON BOTH T-CELLS AND PATHOLOGICAL CELLS AND THERAPEUTIC ANTIBODY AGAINST SAID ANTIGEN
The present invention relates to a therapeutic combination of immune cells, preferably allogeneic non-alloreactive TCR-KO immune T cells, wherein a gene coding an antigen marker X present on both T-cells and pathological cells is inactivated and a corresponding therapeutic antibody specific for said antigen marker X, method for preparing the same and use in immunotherapy.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
61.
TAL-effector nuclease (TALEN)-modified allogenic cells suitable for therapy
The invention relates to the fields of immunotherapy, molecular biology and recombinant nucleic acid technology. In particular, the invention relates to a TALEN-modified human primary cell comprising in its genome, a modified human T cell receptor alpha gene with an insertion comprising at least, from 5′ to 3′, a polynucleotide encoding a self-cleaving peptide, a chimeric antigen receptor, wherein the cell has undetectable cell-surface expression of the endogenous alpha beta T cell receptor as compared to a TCR positive control cell and expresses a receptor to target a pathological cell, use of said cell for treating a disease, including cancer. The invention further relates to methods for producing such a TALEN-modified cell, and to means for detecting such an engineered human primary cell or other genetically modified human primary cell obtained using alternative and/or additional rare cutting endonucleases.
The invention pertains to the field of adaptive cell immunotherapy. It aims at reducing the occurrence of translocations and cell deaths when several specific endonuclease reagents are used altogether to genetically modify primary immune cells at different genetic loci. The method of the invention allows to yield safer immune primary cells harboring several genetic modifications, such as triple or quadruple gene inactivated cells, from populations or sub-populations of cells originating from a single donor or patient, for their subsequent use in therapeutic treatments.
The present invention relates to engineered immune cells expressing new mesothelin (MLSN) specific chimeric antigen receptors (anti-mesothelin CAR) and their use in the treatment of solid tumors, particularly suited for allogeneic cell immunotherapy.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present invention relates to methods for developing engineered T-cells for immunotherapy and more specifically to methods for modifying T-cells by inactivating at immune checkpoint genes, preferably at least two selected from different pathways, to increase T-cell immune activity This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to highly efficient adoptive immunotherapy strategies for treating cancer and viral infections.
The present invention relates to methods for developing engineered T-cells for immunotherapy that are non-alloreactive. The present invention relates to methods for modifying T-cells by inactivating both genes encoding T-cell receptor and an immune checkpoint gene to unleash the potential of the immune response. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Hyper-lgE syndrome (HIES). In particular, the present invention provides means and methods for genetically modifying HSCs or T-cells involving gene editing reagents, such as TALE-nucleases, that specifically target an endogenous STATS gene comprising at least one mutation causing Hyper-lgE syndrome (HIES), thereby allowing the restoration of the normal cellular phenotype. The present invention also provides populations of engineered HSCs or T-cells which comprise cells comprising an exogenous polynucleotide sequence comprising at least a partial or complete sequence of a functional STATS gene, said exogenous polynucleotide sequence being integrated in an endogenous STATS gene comprising at least one mutation causing Hyper-lgE syndrome (HIES), resulting in the expression of a functional STATS polypeptide. The present invention further provides pharmaceutical compositions comprising the cell populations of the invention, and their use in gene therapy for the treatment of Hyper-lgE syndrome (HIES).
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Severe Combined Immunodeficiency (SCID) related to RAG1. Particularly, the present invention pertains to the treatment of RAG1 deficiency in long-term repopulating hematopoietic stem cells (HSCs). The present invention provides means and methods for genetically modifying HSCs involving gene editing reagents, such as TALE-nucleases, that specifically target a non-functional endogenous RAG1 gene, comprising at least one mutation causing Severe Combined Immunodeficiency (SCID), thereby allowing the restoration of the normal cellular phenotype. The present invention also provides engineered RAG1-edited HSCs comprising an exogenous sequence comprising a nucleic acid sequence encoding a functional RAG1 protein which is integrated in said HSCs' genome into a non-functional RAG1 endogenous locus, resulting in the expression of a functional RAG1 polypeptide. The present invention further provides populations of cells comprising said engineered HSCs, pharmaceutical compositions comprising said engineered HSCs or populations of cells, as well as their use in gene therapy for the treatment of Severe Combined Immunodeficiency (SCID) related to RAG1.
The invention relates to methods of treatment of a solid tumor in a patient in need thereof, comprising administering to the patient: (i) an effective amount of engineered immune cells originating from a donor expressing at their cell surface a Chimeric Antigen Receptor (CAR) directed against Fibroblast Activation Protein (FAP), and (ii) an effective amount of an immunotherapy treatment that elicits an immune response in the patient.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
69.
GENE THERAPY FOR THE TREATMENT OF HYPER-IgE SYNDROME (HIES) BY TARGETED GENE INTEGRATION
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Hyper-lgE syndrome (HIES). In particular, the present invention provides means and methods for genetically modifying HSCs or T-cells involving gene editing reagents, such as TALE-nucleases, that specifically target an endogenous STATS gene comprising at least one mutation causing Hyper-lgE syndrome (HIES), thereby allowing the restoration of the normal cellular phenotype. The present invention also provides populations of engineered HSCs or T-cells which comprise cells comprising an exogenous polynucleotide sequence comprising at least a partial or complete sequence of a functional STATS gene, said exogenous polynucleotide sequence being integrated in an endogenous STATS gene comprising at least one mutation causing Hyper-lgE syndrome (HIES), resulting in the expression of a functional STATS polypeptide. The present invention further provides pharmaceutical compositions comprising the cell populations of the invention, and their use in gene therapy for the treatment of Hyper-lgE syndrome (HIES).
The present invention generally relates to the field of genome engineering (gene editing), and more specifically to gene therapy for the treatment of Severe Combined Immunodeficiency (SCID) related to RAG1. Particularly, the present invention pertains to the treatment of RAG1 deficiency in long-term repopulating hematopoietic stem cells (HSCs). The present invention provides means and methods for genetically modifying HSCs involving gene editing reagents, such as TALE-nucleases, that specifically target a non-functional endogenous RAG1 gene, comprising at least one mutation causing Severe Combined Immunodeficiency (SCID), thereby allowing the restoration of the normal cellular phenotype. The present invention also provides engineered RAG1-edited HSCs comprising an exogenous sequence comprising a nucleic acid sequence encoding a functional RAG1 protein which is integrated in said HSCs' genome into a non-functional RAG1 endogenous locus, resulting in the expression of a functional RAG1 polypeptide. The present invention further provides populations of cells comprising said engineered HSCs, pharmaceutical compositions comprising said engineered HSCs or populations of cells, as well as their use in gene therapy for the treatment of Severe Combined Immunodeficiency (SCID) related to RAG1.
The invention relates to methods of treatment of a solid tumor in a patient in need thereof, comprising administering to the patient: (i) an effective amount of engineered immune cells originating from a donor expressing at their cell surface a Chimeric Antigen Receptor (CAR) directed against Fibroblast Activation Protein (FAP), and (ii) an effective amount of an immunotherapy treatment that elicits an immune response in the patient.
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention relates to the design of improved TALE protein fusions useful as sequence-specific genomic reagents, such as TALE-nucleases and TALE base editors, displaying higher on-target/off-target activity ratios. Its goal is to produce safer reagents to genetically modify the genomes of different types of cells, especially mammalian cells, in particular for their use in gene therapy.
A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
The present invention relates to genetically engineered immune cells expressing new anti-MUC1 chimeric antigen receptors and their use in the treatment of solid tumors, particularly suited for allogeneic cell immunotherapy.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
75.
NEW ANTI-MUC1 CARS AND GENE EDITED IMMUNE CELLS FOR SOLID TUMORS CANCER IMMUNOTHERAPY
The present invention relates to genetically engineered immune cells expressing new anti-MUC1 chimeric antigen receptors and their use in the treatment of solid tumors, particularly suited for allogeneic cell immunotherapy.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of genetically modified TILs with reduced expression of CISH and optionally PD-1 as described herein.
The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of genetically modified TILs with reduced expression of CISH and optionally PD-1 as described herein.
The present invention provides composition kits and methods for treating cancer in a human by immunotherapy using successive doses of CAR-T cells with no or reduced anamnestic immune reaction in one individual (P).
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
79.
USE OF PRE T ALPHA OR FUNCTIONAL VARIANT THEREOF FOR EXPANDING TCR ALPHA DEFICIENT T CELLS
A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
80.
USE OF AMINOQUINOLINE COMPOUNDS FOR HIGHER GENE INTEGRATION
The invention provides aminoquinoline compounds as powerful enhancers of genetic recombination in living cells, especially to perform site-directed gene integration of exogenous DNA template by homologous recombination. In particular, disclosed are methods by which cells are treated with chloroquine and/or hydroxychloroquine prior to, or concomitantly with, the introduction of exogenous DNA templates, and optionally in presence of rare-cutting endonucleases, to obtain higher rates of gene integration or correction.
The present invention concerns new engineered immune cells expressing two CARs directed against two different targets, polynucleotides for preparing said immune cells, pharmaceutical compositions comprising said immune cells, and the use of said immune cells in the treatment of cancers.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present invention concerns new engineered immune cells expressing two CARs directed against two different targets, polynucleotides for preparing said immune cells, pharmaceutical compositions comprising said immune cells, and the use of said immune cells in the treatment of cancers.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The invention relates to therapeutic compositions for allogeneic cellular therapy comprising TCR deficient T-cells, which are genetically engineered to express immune cell engagers, and methods related thereto.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention relates to a method for the generation of compact Transcription Activator-Like Effector Nucleases (TALENs) that can efficiently target and process double-stranded DNA. More specifically, the present invention concerns a method for the creation of TALENs that consist of a single TALE DNA binding domain fused to at least one catalytic domain such that the active entity is composed of a single polypeptide chain for simple and efficient vectorization and does not require dimerization to target a specific single double-stranded DNA target sequence of interest and process DNA nearby the DNA target sequence. The present invention also relates to compact TALENs, vectors, compositions and kits used to implement the method.
The invention relates to a new potency assay for characterizing the quality and activity of an immune cell expressing a chimeric antigen receptor, the kit to carry out this assay and uses thereof.
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
86.
METHODS FOR TARGETED INSERTION OF EXOGENOUS SEQUENCES IN CELLULAR GENOMES
The present disclosure provides methods for targeted insertion of an exogenous sequence at a genomic locus in a cell, wherein said insertion is induced by a sequence- specific endonuclease that has cleavage activity at said locus, at least 5 hours before the introduction into said cell of a DNA template comprising said exogenous sequence.
The present disclosure provides methods for targeted insertion of an exogenous sequence at a genomic locus in a cell, wherein said insertion is induced by a sequence- specific endonuclease that has cleavage activity at said locus, at least 5 hours before the introduction into said cell of a DNA template comprising said exogenous sequence.
The present disclosure provides methods to genetically modify cells by insertion of an artificial exon (ArtEx) for delivery of therapeutic proteins in specific cell types and more particularly engineered cells for expression of a transgene into the brain of a patient.
The present disclosure provides methods to genetically modify cells by insertion of an artificial exon (ArtEx) for delivery of therapeutic proteins in specific cell types and more particularly engineered cells for expression of a transgene into the brain of a patient.
09 - Scientific and electric apparatus and instruments
10 - Medical apparatus and instruments
Goods & Services
Scientific, research, or production apparatus and
instruments for pharmaceuticals; electric and fluidic
devices for transferring molecules and devices for
detecting, selecting and/or sorting cells in which molecules
are transferred; pulse generators and electric fields for
transferring chemical or biological molecules into living
cells, integration of foreign nucleic acids into the genome
of living cells and transient production of proteins or
nucleic acids; apparatus and instruments designed for
electroporation; electroporation apparatus and peripheral
equipment relating thereto; apparatus and instruments for
conducting, switching, transforming, accumulating,
controlling and monitoring electricity, in particular
electric capacitors, transistors, power semiconductors,
relays, transformers, electric contacts and conductors,
electric control and measuring instruments; laboratory
apparatus and instruments; reaction devices, containers and
vessels for biochemical use (for laboratories and other than
for medical use) in particular for transferring chemical or
biological molecules into living cells, integrating foreign
nucleic acids into the genome of living cells and transient
production of proteins or nucleic acids; test tubes; metal
electrodes and conductive polymers not for medical use;
vessels of synthetic materials for laboratory use and other
than for medical purposes; vessels, including those with
electrodes of metal and conductive polymers, for biochemical
use (for laboratory and other than for medical use);
containers and reaction vessels having several reaction
chambers, including those having electrodes of metal and
conductive polymers, for biochemical use (for laboratory and
other than for medical use); multi-well plates including
those having electrodes of metal and conductive polymers,
for biochemical use (other than for medical use); magnetic
recording media; diskettes, compact discs, DVDs and other
data carriers; data processing devices and computers;
computer peripherals; computer programs and software. Electric and electronic apparatus and instruments for
medical use, for electroporation treatment; pump device
connected to an electroporator via a cable system for
collecting cells for medical use; electrostimulation
apparatus for therapeutic treatment, for medical or clinical
use for the treatment of genetic defects in gene therapy;
pulse generators and electric fields for transferring
chemical or biological molecules into living cells in
combatting infectious and viral diseases, cardiovascular
diseases and cancer, integration of foreign nucleic acids
into the genome of living cells and transient production of
proteins or nucleic acids; apparatus and instruments
designed for electroporation, in particular electroporation
apparatus and peripheral equipment relating thereto; medical
apparatus and instruments; reaction devices, containers and
vessels for medical use; reaction devices, containers and
vessels for medical use for transferring chemical or
biological molecules into living cells, integration of
foreign nucleic acids into the genome of living cells and
transient production of proteins or nucleic acids; tubes
for medical use; metal electrodes and conductive polymers
for medical use; vessels of synthetic materials for medical
use; vessels, including those with electrodes of metal and
conductive polymers, for medical use; reaction containers
and vessels with several reaction chambers, including those
with electrodes of metal and conductive polymers, for
medical use; multi-well plates, including those with
electrodes of metal and conductive polymers, for medical
use.
92.
CHIMERIC ANTIGEN RECEPTORS (CAR)-EXPRESSING CELLS AND COMBINATION TREATMENT FOR IMMUNOTHERAPY OF PATIENTS WITH RELAPSE REFRACTORY ADVERSE GENETIC RISK AML
The present invention relates to compositions comprising engineered allogenic immune cells endowed with Chimeric Antigen Receptors (CAR), in particular a CAR specific for CD123 and CLL1 for treating AML patients with adverse genetic risk.
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
93.
Use of pre T alpha or functional variant thereof for expanding TCR alpha deficient T cells
A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Chemicals and biochemical products for industrial and
scientific use for transferring biological molecules into
living cells and for integrating foreign nucleic acids into
the genome of living cells; chemical and/or biochemical
soluble substances and solutions for industrial use for the
transfer of chemical or biological molecules into living
cells and the integration of foreign nucleic acids into the
genome of living cells; biological agents for laboratory
use (other than for medical and veterinary use); diagnostic
products (other than for medical and veterinary use);
peptides, proteins and nucleic acids or complexes of these
molecules intended for identifying genetic expression and
protein location and integration of foreign nucleic acids
into the genome of living cells; chemical and biochemical
preparations for industrial and scientific use; chemical
and/or biochemical soluble substances and solutions for
industrial use; standard solutions and buffers for
transferring chemical or biological molecules into living
cells, integration of foreign nucleic acids into the genome
of living cells and transient production of proteins or
nucleic acids; aqueous solutions containing nutrients for
cultivating living cells; biological agents for laboratory
use other than for medical and veterinary use; diagnostic
products other than for medical and veterinary use;
peptides, proteins and nucleic acids or complexes of these
molecules, in particular for detecting and monitoring, and
for integrating foreign nucleic acids into the genome of
living cells and transient production of proteins;
transfection reagents, in particular for transient
production of proteins, other than for medical and
veterinary use. Pharmaceutical and veterinary preparations; diagnostic
products for medical and veterinary use; living cells and
microorganisms as well as proteins, peptides and nucleic
acids or complexes of these molecules for medical and
veterinary use; living cells and microorganisms as well as
proteins, peptides and nucleic acids or complexes of these
molecules for medical and clinical use for the treatment of
genetic defects in gene therapy, viral and infectious
diseases, cardiovascular diseases and cancer; diagnostic
preparations for medical and veterinary use, in particular
for the diagnosis and analysis of genetic defects, viral and
infectious diseases, cardiovascular diseases and cancer;
living cells, microorganisms, and proteins, peptides and
nucleic acids or complexes of these molecules for medical
and veterinary use, in particular for medical and clinical
use for the treatment of genetic defects in gene therapy,
viral and infectious diseases, cardiovascular diseases and
cancer.
95.
NEW MESOTHELIN SPECIFIC CHIMERIC ANTIGEN RECEPTORS (CAR) FOR SOLID TUMORS CANCER IMMUNOTHERAPY
The present invention relates to engineered immune cells expressing new mesothelin (MLSN) specific chimeric antigen receptors (anti-mesothelin CAR) and their use in the treatment of solid tumors, particularly suited for allogeneic cell immunotherapy.
The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a CD123 monoclonal antibody, conferring specific immunity against CD123 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
The present invention relates to an engineered immune cell endowed with CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
99.
Methods for engineering T cells for immunotherapy by using RNA-guided Cas nuclease system
The present invention relates to methods of developing genetically engineered, preferably non-alloreactive T-cells for immunotherapy. This method involves the use of RNA-guided endonucleases, in particular Cas9/CRISPR system, to specifically target a selection of key genes in T-cells. The engineered T-cells are also intended to express chimeric antigen receptors (CAR) to redirect their immune activity towards malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer and viral infections.
The invention pertains to the field of adoptive cell immunotherapy. It provides with engineered immune cells comprising genetic alteration into genes which are involved into immune functions downregulation, especially in response to environment signals such as nutrients depletion. Such method allows the production of more potent immune cells in the context of tumors' microenvironment.
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
