METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION

    公开(公告)号:US20240026376A1

    公开(公告)日:2024-01-25

    申请号:US18480890

    申请日:2023-10-04

    Applicant: CELLECTIS

    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. 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.

    ANTI-HBV COMBINATION THERAPIES INVOLVING SPECIFIC ENDONUCLEASES

    公开(公告)号:US20210139870A1

    公开(公告)日:2021-05-13

    申请号:US16623171

    申请日:2018-06-18

    Applicant: CELLECTIS

    Abstract: The invention pertains to non-viral methods for in vivo delivery of endonuclease reagents compositions to specific tissues or cells. According to the invention, the endonuclease reagents are preferably encapsulated into micelle structures of 50 to 150 nm diameter for intravenous injection, in combination with antiviral compounds. The invention thereby provides therapeutic compositions comprising endonuclease reagents and antiviral compounds for effective elimination of HBV from liver cells and treatment of chronic hepatitis.

    METHOD FOR IMPROVING PRODUCTION OF CAR T CELLS

    公开(公告)号:US20200332004A1

    公开(公告)日:2020-10-22

    申请号:US16958250

    申请日:2018-12-28

    Applicant: CELLECTIS

    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.

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