Abstract: 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.

Abstract: The invention provides CARs (CARs) that specifically bind to BCMA (B-Cell Maturation Antigen). The invention further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The invention further relates to therapeutic methods for use of these CARs and engineered immune cells for the treatment of a condition associated with malignant cells expressing BCMA (e.g., cancer).

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to polypeptides and more particularly to Transcription Activator-Like Effector derived proteins that allow to efficiently target and/or process nucleic acids. The present invention also concerns methods to use these proteins. The present invention also relates to vectors, compositions and kits in which RVD domains and Transcription Activator-Like Effector (TALE) proteins of the present invention are used.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The invention provides CARs (CARs) that specifically bind to BCMA (B-Cell Maturation Antigen). The invention further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The invention further relates to therapeutic methods for use of these CARs and engineered immune cells for the treatment of a condition associated with malignant cells expressing BCMA (e.g., cancer).

Abstract: The invention provides CARs (CARs) that specifically bind to BCMA (B-Cell Maturation Antigen). The invention further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The invention further relates to therapeutic methods for use of these CARs and engineered immune cells for the treatment of a condition associated with malignant cells expressing BCMA (e.g., cancer).

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to new Transcription Activator-Like Effector proteins and more particularly new Transcription Activator-Like Effector Nucleases (TALENs) that can efficiently target and process nucleic acids. The present invention also concerns methods to use these new Transcription Activator-Like Effector proteins. The present invention also relates to vectors, compositions and kits in which Transcription Activator-Like Effector proteins of the present invention are used.

Abstract: 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.

Abstract: The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward CLL1 positive cells. The engineered immune cells endowed with such CARs are particularly suited for immunotherapy for treating cancer, in particular leukemia.

Abstract: The present invention relates to the field of cell immunotherapy and more particularly to a new generation of chimeric antigen receptors (CAR), allowing the control of immune cells endowed with such CARs through the interaction with small molecules. More particularly, the present invention relates to chimeric antigen receptor which comprise in at least one ectodomain a molecular switch turning the antigen binding function of the receptor from an off to on state, and vice versa. The present invention thus provides more controlled and potentially safer engineered CAR endowed immune cells, such as T-lymphocytes.

Abstract: The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) into genetically engineered immune cells to prevent cytokine release syndrome to arise during the course of cell therapy. These exogenous coding sequences are more particularly soluble human polypeptides placed 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.

Abstract: The present invention relates to Transcription Activator-Like Effector (TALE) derived proteins that allow efficient targeting and/or processing of double stranded nucleic acid sequences. The proteins of the invention are typically chimeric protein monomers composed of a core scaffold comprising Repeat Variable Dipeptide regions (RVDs) having binding specificity to a DNA target sequence, to which is fused a catalytic domain to its N-terminus. This later catalytic domain, which can be a monomer of a nuclease, is placed at this position to possibly interact with another catalytic domain fused to another TAL monomer, such that, when the monomers are binding to their respective target DNA sequences, both catalytic domains form a catalytic entity likely to process DNA in the proximity of these target sequences. This new TAL architecture makes it possible to target only one DNA strand, which is not the case, for instance, with classical TALEN architectures.