公开(公告)号：US20210060080A1

公开(公告)日：2021-03-04

申请号：US17099614

申请日：2020-11-16

Applicant: Cellectis

Inventor： Roman GALETTO ,  Julianne SMITH ,  Andrew SCHARENBERG ,  Cécile SCHIFFER-MANNIOUI

IPC: A61K35/17 ,  C07K14/705 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28

Abstract: 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 Receptor 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.

公开(公告)号：US20190389959A1

公开(公告)日：2019-12-26

申请号：US16406859

申请日：2019-05-08

Applicant: Cellectis

Inventor： Roman GALETTO

IPC: C07K16/28 ,  C12N5/0783 ,  C07K14/705 ,  C07K14/725 ,  A61K35/17

Abstract: 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 BCMA monoclonal antibody, conferring specific immunity against BCMA positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas, multiple myeloma and leukemia.

公开(公告)号：US20180320138A1

公开(公告)日：2018-11-08

申请号：US15773960

申请日：2016-11-07

Applicant: CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED (CIBER) ,  CENTRO DE INVESTIGACIONES ENERGÉTICAS, MEDIOAMBIENTALES Y TECNOLÓGICAS ,  FUNDACIÓN INSTITUTO DE INVESTIGACIÓ SANITARIA FUNDACIÓN JIMÉNEZ DÍAZ ,  CELLECTIS

Inventor： José Carlos SEGOVIA SANZ ,  Oscar QUINTANA BUSTAMANTE ,  Zita Maite GÁRATE MUTILOA ,  Juan Antonio BUEREN RONCERO ,  Brian R. DAVIS ,  Roman GALETTO ,  Agnes GOUBLE ,  Laurent POIROT

IPC: C12N5/0789 ,  C12N5/074

CPC classification number: C12N5/0647 ,  C12N5/0696 ,  C12N2500/25 ,  C12N2501/105 ,  C12N2501/113 ,  C12N2501/115 ,  C12N2501/125 ,  C12N2501/14 ,  C12N2501/145 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/165 ,  C12N2501/22 ,  C12N2501/2303 ,  C12N2501/2311 ,  C12N2501/26 ,  C12N2501/415 ,  C12N2501/602 ,  C12N2501/603 ,  C12N2501/604 ,  C12N2501/606 ,  C12N2501/727 ,  C12N2501/91 ,  C12N2506/11 ,  C12N2506/45 ,  C12N2510/00

Abstract: The present invention relates to the medical field, in particular to gene editing as a therapeutic approach for the treatment of metabolic diseases affecting the erythroid lineage in a mammalian subject. In invention particular embodiment it refers to the combination of cell reprograming and gene editing for PKD correction as a first example of the potential application of these advanced technologies to metabolic diseases affecting the erythroid lineage. In this sense, PKD patient-specific iPSCs were efficiently generated from PB-MNCs (peripheral blood mononuclear cells) by a SeV non-integrative system and efficiently use to treat pyruvate kinase deficiency. The gene editing strategy for PKLR gene correction was also successfully applied directly to hematopoietic progenitors.

公开(公告)号：US20160120905A1

公开(公告)日：2016-05-05

申请号：US14889686

申请日：2014-05-13

Applicant: CELLECTIS

Inventor： Roman GALETTO ,  Agnes GOUBLE ,  Stephanie GROSSE ,  Cécile SCHIFFER-MANNIOUI ,  Laurent POIROT ,  Andrew SCHARENBERG ,  Julianne SMITH

IPC: A61K35/17 ,  C12N5/0783

CPC classification number: A61K35/17 ,  A61K38/00 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70521 ,  C07K14/70578 ,  C07K16/28 ,  C07K16/2803 ,  C07K2317/14 ,  C07K2317/24 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/03 ,  C07K2319/74 ,  C12N5/0636 ,  C12N2501/39 ,  C12N2501/51 ,  C12N2501/515 ,  C12N2501/599 ,  C12N2502/99 ,  C12N2510/00

Abstract: 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.

Abstract translation: 本发明涉及用于开发非同种异体反应的用于免疫治疗的工程化T细胞的方法。 本发明涉及通过使编码T细胞受体的两个基因和免疫检查点基因失活来释放免疫应答的潜力来修饰T细胞的方法。 该方法包括使用特定的稀有切割内切核酸酶，特别是TALE-核酸酶（TAL效应子内切核酸酶）和编码这种多肽的多核苷酸，以精确地靶向T细胞中的关键基因的选择，其可从供体或从原代培养获得 细胞。 本发明开启了治疗癌症和病毒感染的标准和负担得起的过继免疫治疗策略的方法。

公开(公告)号：US20220348955A1

公开(公告)日：2022-11-03

申请号：US17848590

申请日：2022-06-24

Applicant: Cellectis

Inventor： Roman GALETTO ,  Agnes GOUBLE ,  Stephanie GROSSE ,  Cecile MANNIOUI ,  Laurent POIROT ,  Andrew SCHARENBERG ,  Julianne SMITH

IPC: C12N15/85 ,  A61K35/17 ,  C07K14/705 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28

Abstract: 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.

公开(公告)号：US20200281979A1

公开(公告)日：2020-09-10

申请号：US16876079

申请日：2020-05-17

Applicant: Cellectis

Inventor： Roman GALETTO ,  Agnes GOUBLE ,  Stephanie GROSSE ,  Cecile MANNIOUI ,  Laurent POIROT ,  Andrew SCHARENBERG ,  Julianne SMITH

IPC: A61K35/17 ,  C07K14/705 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28

Abstract: Methods for developing engineered T-cells for immunotherapy that are both non-alloreactive and resistant to immunosuppressive 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.

公开(公告)号：US20190002561A1

公开(公告)日：2019-01-03

申请号：US15926755

申请日：2018-03-20

Applicant: CELLECTIS

Inventor： Roman GALETTO

IPC: C07K16/28 ,  C07K14/705

Abstract: 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.

公开(公告)号：US20180360883A1

公开(公告)日：2018-12-20

申请号：US16027629

申请日：2018-07-05

Applicant: Cellectis

Inventor： Roman GALETTO ,  Agnes GOUBLE ,  Stephanie GROSSE ,  Cecile MANNIOUI ,  Laurent POIROT ,  Andrew SCHARENBERG ,  Julianne SMITH

IPC: A61K35/17 ,  C07K14/705 ,  C12N5/0783 ,  C07K16/28 ,  C07K14/725

Abstract: Methods for developing engineered T-cells for immunotherapy that are both non-alloreactive and resistant to immunosuppressive 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.

公开(公告)号：US20160145337A1

公开(公告)日：2016-05-26

申请号：US14891296

申请日：2014-05-12

Applicant: CELLECTIS

Inventor： Roman GALETTO ,  Julianne SMITH ,  Andrew SCHARENBERG ,  Cècile SCHIFFER-MANNIOUI

IPC: C07K16/28 ,  C07K14/725 ,  C07K14/705

CPC classification number: A61K35/17 ,  A61K38/00 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70521 ,  C07K14/70578 ,  C07K16/28 ,  C07K16/2803 ,  C07K2317/14 ,  C07K2317/24 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/03 ,  C07K2319/74 ,  C12N5/0636 ,  C12N2501/39 ,  C12N2501/51 ,  C12N2501/515 ,  C12N2501/599 ,  C12N2502/99 ,  C12N2510/00

Abstract: 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 Receptor 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.

Abstract translation: 本发明涉及嵌合抗原受体（CAR）。 CAR能够将免疫细胞特异性和反应性转向利用配体结合结构域性质的选定靶标。 特别地，本发明涉及嵌合抗原受体，其中细胞外配体结合是衍生自CD19单克隆抗体的scFV，优选4G7。 本发明还涉及多核苷酸，编码所述CAR的载体和在其表面表达所述CAR的分离的细胞。 本发明还涉及用于在其表面上工程化表达4G7-CAR的免疫细胞的方法，其赋予转导细胞上延长的“活化”状态。 本发明特别可用于治疗B细胞淋巴瘤和白血病。

公开(公告)号：US20160120906A1

公开(公告)日：2016-05-05

申请号：US14894426

申请日：2014-05-13

Applicant: CELLECTIS

Inventor： Roman GALETTO ,  Agnes GOUBLE ,  Stephanie GROSSE ,  Cécile SCHIFFER-MANNIOUI ,  Laurent POIROT ,  Andrew SCHARENBERG ,  Julianne SMITH

IPC: A61K35/17 ,  C12N9/22

CPC classification number: A61K35/17 ,  A61K2035/124 ,  C07K2319/80 ,  C12N5/0636 ,  C12N9/22 ,  C12N2501/39 ,  C12N2501/51 ,  C12N2501/515 ,  C12N2501/599 ,  C12N2502/99 ,  C12N2510/00

Abstract: 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.

Abstract translation: 本发明涉及用于发展用于免疫治疗的工程化T细胞的方法，更具体地涉及通过在免疫检查点基因（优选至少两个选自不同途径）中灭活来增加T细胞免疫活性来修饰T细胞的方法。 该方法包括使用特定的稀有切割内切核酸酶，特别是TALE-核酸酶（TAL效应子内切核酸酶）和编码这种多肽的多核苷酸，以精确地靶向T细胞中的关键基因的选择，其可从供体或从原代培养获得 细胞。 本发明开辟了一种治疗癌症和病毒感染的高效过继免疫治疗策略。