公开(公告)号：US20150203817A1

公开(公告)日：2015-07-23

申请号：US14403937

申请日：2013-05-13

Applicant: Cellectis

Inventor： Roman Galetto ,  Agnes Gouble ,  Stephanie Grosse ,  Cecile Mannioui ,  Laurent Poirot ,  Andrew Scharenberg ,  Julianne Smith

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

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.

Abstract translation: 通过将pTα或其功能变体表达到所述细胞中来扩增TCRalpha缺陷型T细胞的方法，从而恢复功能性CD3复合物。 该方法对于提高使用来自供体的原代T细胞的免疫治疗的效率特别有用。 该方法涉及使用pTα或其功能变体和编码这些多肽的多核苷酸来扩增TCRα缺陷型T细胞。 这样的工程细胞可以通过使用特异性稀释内切核酸酶，优选TALE-核酸酶来获得。 在这样的工程细胞中使用嵌合抗原受体（CAR），特别是多链CAR来靶向恶性或感染细胞。 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：US20140134142A1

公开(公告)日：2014-05-15

申请号：US14018021

申请日：2013-09-04

Applicant: CELLECTIS

Inventor： Julianne Smith ,  Andrew Scharenberg ,  Cecile Mannioui ,  Justin Eyquem

IPC: 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: The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs. Such CARs, which aim to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties, comprise separate extracellular ligand binding and signaling domains in different transmembrane polypeptides. The signaling domains are designed to assemble in juxtamembrane position, which forms flexible architecture closer to natural receptors, that confers optimal signal transduction. The invention encompasses the polynucleotides, vectors encoding said multi-chain CAR and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer and viral infections.

Abstract translation: 本发明涉及称为多链CAR的新一代嵌合抗原受体（CAR）。 旨在将免疫细胞特异性和反应性转向使用配体结合结构域性质的选定靶标的这样的CAR在不同跨膜多肽中包含分离的细胞外配体结合和信号结构域。 信号域被设计为在并置位置组装，其形成更接近天然受体的柔性结构，其赋予最佳信号转导。 本发明包括多核苷酸，编码所述多链CAR的载体和在其表面表达它们的分离细胞，特别是其用于免疫治疗。 本发明开创了治疗癌症和病毒感染的有效过继性免疫治疗策略的途径。

公开(公告)号：US11603539B2

公开(公告)日：2023-03-14

申请号：US13892805

申请日：2013-05-13

Applicant: CELLECTIS

Inventor： Roman Galetto ,  Agnès Gouble ,  Stéphanie Grosse ,  Cécile Mannioui ,  Laurent Poirot ,  Andrew Scharenberg ,  Julianne Smith

IPC: C12N15/63 ,  C07H21/04 ,  C12N15/85 ,  A61K35/17 ,  C07K14/705 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  A61K48/00 ,  A61K39/00 ,  A61K38/00

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：US11311575B2

公开(公告)日：2022-04-26

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: A61K48/00 ,  C07H21/04 ,  A61K35/17 ,  C12N9/22 ,  C12N5/0783 ,  A01K67/00 ,  A61K35/12

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：US11274316B2

公开(公告)日：2022-03-15

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: C12N15/85 ,  A61K35/17 ,  C07K14/705 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  A61K39/00 ,  A61K38/00

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：US11077144B2

公开(公告)日：2021-08-03

申请号：US17099608

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 ,  A61K39/00 ,  A61K38/00

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.

公开(公告)号：US10363270B2

公开(公告)日：2019-07-30

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: A61K48/00 ,  C07H21/04 ,  C12N15/87 ,  A61K35/17 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  C07K14/705 ,  A01K67/00 ,  A61K38/00

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.