Abstract: 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.

Abstract: 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.

Abstract: 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.

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 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).

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 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.

Abstract: 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).

Abstract: 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.

Abstract: 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.

Abstract: 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.

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 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.

Abstract: 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.

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 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.

Abstract: 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.

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 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.