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    METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION
    1.
    发明申请
    METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION 审中-公开

    公开(公告)号：US20190010514A1

    公开(公告)日：2019-01-10

    申请号：US16138908

    申请日：2018-09-21

    Applicant: CELLECTIS

    Inventor： Laurent POIROT ,  David SOURDIVE ,  Philippe DUCHATEAU ,  Jean-Pierre CABANIOLS

    IPC: C12N15/85 ,  C12N5/0783 ,  C07K14/74 ,  C12N15/90 ,  C07K14/705 ,  C12N15/113

    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 H2M 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.

    METHOD FOR GENERATING BATCHES OF ALLOGENEIC T-CELLS WITH AVERAGED POTENCY
    3.
    发明申请
    METHOD FOR GENERATING BATCHES OF ALLOGENEIC T-CELLS WITH AVERAGED POTENCY 审中-公开
    用于产生具有平均斑点的同种异体T细胞的批量的方法

    公开(公告)号：US20160296563A1

    公开(公告)日：2016-10-13

    申请号：US15038025

    申请日：2014-11-21

    Applicant: CELLECTIS

    Inventor： David SOURDIVE ,  Carole DESSEAUX ,  Andrew SCHARENBERG

    IPC: A61K35/17 ,  C07K14/725 ,  C12N5/0783

    CPC classification number: A61K35/17 ,  A61K2039/5158 ,  C07K14/7051 ,  C12N5/0636 ,  C12N2510/00 ,  C12N2510/02

    Abstract: The present invention relates to a method for generating batches of lymphocytes with averaged potency. In particular, the present invention relates to a method of pooling lymphocytes from different donors to avoid NK alloreactivity and anti-HLA immune response. Lymphocytes from each donor are inactivated for at least a gene encoding a TCR component, and are pooled together before be administrated to a subject in need thereof. Thus, this method allows generating batches of lymphocytes with averaged potency, particularly to treat cancer, viral infection or auto-immune disease. The present invention also relates to a batch of lymphocytes obtainable by this method. The batch of lymphocytes can be used to be administrated to one or several patients, being made available as an “off the shelf” therapeutic product, in particular to treat cancer, auto-immune disease or viral infection.

    Abstract translation: 本发明涉及产生具有平均效力的淋巴细胞批次的方法。 特别地，本发明涉及汇集来自不同供体的淋巴细胞以避免NK同种异体反应性和抗HLA免疫应答的方法。 来自每个供体的淋巴细胞灭活至少一个编码TCR组分的基因，并在合并给有需要的受试者之前汇集在一起​​。 因此，该方法允许产生具有平均效力的淋巴细胞的批次，特别是治疗癌症，病毒感染或自身免疫疾病。 本发明还涉及可通过该方法获得的一批淋巴细胞。 该批淋巴细胞可以用于给一个或几个患者施用，其可作为“现成”治疗产品获得，特别是用于治疗癌症，自身免疫疾病或病毒感染。

    METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION
    6.
    发明公开
    METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION 审中-公开

    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

    Inventor： Laurent POIROT ,  David SOURDIVE ,  Philippe DUCHATEAU ,  Jean-Pierre CABANIOLS

    IPC: C12N15/85 ,  C07K14/74 ,  C12N5/0783 ,  C07K14/705 ,  C12N15/113 ,  C12N15/90

    CPC classification number: C12N15/85 ,  C07K14/70539 ,  C12N5/0636 ,  C07K14/70503 ,  C12N15/1138 ,  C12N15/907 ,  C07K2317/24 ,  C07K2317/622

    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.

    METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION
    8.
    发明申请
    METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION 审中-公开
    用于产生用于同种异体移植的T细胞的方法

    公开(公告)号：US20170016025A1

    公开(公告)日：2017-01-19

    申请号：US15123974

    申请日：2015-03-11

    Applicant: CELLECTIS

    Inventor： Laurent POIROT ,  David SOURDIVE ,  Philippe DUCHATEAU ,  Jean-Pierre CABANIOLS

    IPC: C12N15/85 ,  C07K14/74 ,  C07K14/705 ,  C12N15/90 ,  C12N15/113

    CPC classification number: C12N15/85 ,  C07K14/70503 ,  C07K14/70539 ,  C07K2317/24 ,  C07K2317/622 ,  C12N5/0636 ,  C12N15/1138 ,  C12N15/907

    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.

    Abstract translation: 本发明涉及工程化T细胞，其制备方法及其作为药物的用途，特别是用于免疫治疗。 本发明的工程化T细胞的特征在于，β2-微球蛋白（B2M）和/或II类主要组织相容性复合反式激活因子（CIITA）的表达受到抑制，例如通过使用能够选择性失活的稀有内切核酸酶 DNA切割编码B2M和/或CIITA的基因，或通过使用抑制B2M和/或CIITA表达的核酸分子。 为了进一步使T细胞非同种异体反应，至少一种编码T细胞受体成分的基因被灭活，例如通过使用能够通过DNA切割选择性失活的稀有切割内切核酸酶来编码所述TCR的基因 零件。 此外，可以对这些修饰的T细胞进行免疫抑制多肽的表达，以延长宿主生物体中这些修饰的T细胞的存活。 这种修饰的T细胞特别适用于同种异体移植，特别是因为它降低宿主免疫系统的排斥风险和发生移植物抗宿主病的风险。 本发明开启了使用T细胞治疗癌症，感染和自身免疫疾病的标准和负担得起的过继免疫治疗策略的方法。

    METHOD OF ENGINEERING CHEMOTHERAPY DRUG RESISTANT T-CELLS FOR IMMUNOTHERAPY
    9.
    发明申请
    METHOD OF ENGINEERING CHEMOTHERAPY DRUG RESISTANT T-CELLS FOR IMMUNOTHERAPY 审中-公开
    工程化疗药物耐药T细胞免疫治疗方法

    公开(公告)号：US20160361359A1

    公开(公告)日：2016-12-15

    申请号：US15037988

    申请日：2014-11-21

    Applicant: CELLECTIS

    Inventor： Julien VALTON ,  Philippe DUCHATEAU ,  David SOURDIVE

    IPC: A61K35/17 ,  C12N5/0783 ,  A61K31/7076

    Abstract: The present invention relates to the use of “off-the-shelf” allogeneic therapeutic cells for immunotherapy in conjunction with chemotherapy to treat patients with cancer. In particular, the inventors develop a method of engineering allogeneic T-cell resistant to chemotherapeutic agents. The therapeutic benefits afforded by this strategy should be enhanced by the synergistic effects between chemotherapy and immunotherapy. In particular, the present invention relates to a method for modifying T-cells by inactivating at least one gene encoding T-cell receptor component and by modifying said T-cells to confer drug resistance. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer.

    Abstract translation: 本发明涉及“现成”同种异体治疗性细胞用于免疫治疗与化疗联合治疗癌症患者的用途。 特别地，本发明人开发了一种对化疗药物耐药的同种异体T细胞的方法。 通过化学疗法和免疫治疗之间的协同效应，可以提高该策略提供的治疗效果。 特别地，本发明涉及通过使至少一种编码T细胞受体成分的基因失活并通过修饰所述T细胞以赋予耐药性来修饰T细胞的方法。 本发明开启了治疗癌症的标准和负担得起的过继免疫治疗策略的方法。

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