公开(公告)号：US20230201260A1

公开(公告)日：2023-06-29

申请号：US18056544

申请日：2022-11-17

Applicant: CELLECTIS

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

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

CPC classification number: A61K35/17 ,  C12N5/0636 ,  C07K16/2803 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70521 ,  C07K14/70578 ,  C07K16/28 ,  C12N15/85 ,  C07K2317/622 ,  C12N2501/51 ,  C12N2501/515 ,  C12N2502/99 ,  C07K2319/00 ,  C12N2501/39 ,  C12N2501/599 ,  A61K38/00

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.

公开(公告)号：US20210000869A9

公开(公告)日：2021-01-07

申请号：US16365588

申请日：2019-03-26

Applicant: CELLECTIS

Inventor： Roman Galetto ,  Julianne SMITH ,  Andrew SCHARENBERG ,  Cecile 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：US20190216854A1

公开(公告)日：2019-07-18

申请号：US16361438

申请日：2019-03-22

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

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: 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：US20180021379A1

公开(公告)日：2018-01-25

申请号：US15711289

申请日：2017-09-21

Applicant: Cellectis

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

IPC: C07K14/725 ,  C12N5/0783 ,  C07K14/705 ,  C07K16/28 ,  A61K38/00

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: 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：US20160222410A1

公开(公告)日：2016-08-04

申请号：US14915434

申请日：2014-09-02

Applicant: CELLECTIS

Inventor： Andrew SCHARENBERG ,  Julianne SMITH ,  Roman GALETTO

IPC: C12N15/86 ,  C12N7/00

CPC classification number: C12N15/86 ,  C12N7/00 ,  C12N2740/17043 ,  C12N2740/17052

Abstract: The present invention relates to viral transformation method, particularly foamy virus-mediated transformation method. The present invention relates to the transfer of transgene into cells by the safe and efficient transfer of RNA encoding foamy components. The present invention has therefore therapeutic interest, especially in the field of gene therapy.

Abstract translation: 本发明涉及病毒转化方法，特别是泡沫病毒介导的转化方法。 本发明涉及通过安全有效地转移编码泡沫组分的RNA将转基因转移到细胞中。 因此，本发明具有治疗兴趣，特别是在基因治疗领域。

公开(公告)号：US20230056268A1

公开(公告)日：2023-02-23

申请号：US17716102

申请日：2022-04-08

Applicant: CELLECTIS

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

IPC: A61K35/17 ,  C12N9/22 ,  C12N5/0783

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.

公开(公告)号：US20210220405A1

公开(公告)日：2021-07-22

申请号：US17198505

申请日：2021-03-11

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: 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：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：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。

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。