公开(公告)号：US10426795B2

公开(公告)日：2019-10-01

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: C12N5/10 ,  A61K38/00 ,  A61K35/17 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  C07K14/705

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：US10342829B2

公开(公告)日：2019-07-09

申请号：US14018021

申请日：2013-09-04

Applicant: CELLECTIS

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

IPC: A61K35/17 ,  A61K38/00 ,  C07K16/28 ,  C07K14/705 ,  C07K14/725 ,  C12N5/0783

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. 91The 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.

公开(公告)号：US11414674B2

公开(公告)日：2022-08-16

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

Abstract: A method of expanding 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：US11007224B2

公开(公告)日：2021-05-18

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 ,  C07K14/725 ,  C07K14/705 ,  C07K16/28 ,  C12N5/0783 ,  A61K38/00 ,  A61K39/00

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：US10517896B2

公开(公告)日：2019-12-31

申请号：US16361370

申请日：2019-03-22

Applicant: Cellectis

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

IPC: A61K35/26 ,  A61K35/17 ,  C07K14/705 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  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：US10357515B2

公开(公告)日：2019-07-23

申请号：US15038025

申请日：2014-11-21

Applicant: CELLECTIS

Inventor： David Sourdive ,  Carole Desseaux ,  Andrew Scharenberg

IPC: A61K35/17 ,  A61K39/00 ,  C07K14/725 ,  C12N5/0783

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.

公开(公告)号：US11891614B2

公开(公告)日：2024-02-06

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: C12N15/87 ,  C07H21/04 ,  C12N15/85 ,  A61K35/17 ,  C07K14/705 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  A01K67/00 ,  A61K39/00 ,  A61K38/00

CPC classification number: C12N15/85 ,  A61K35/17 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70521 ,  C07K14/70578 ,  C07K16/28 ,  C07K16/2803 ,  C12N5/0636 ,  A61K38/00 ,  A61K39/00 ,  C07K2317/14 ,  C07K2317/24 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/03 ,  C07K2319/74 ,  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：US11304975B2

公开(公告)日：2022-04-19

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: A61K48/00 ,  C07H21/04 ,  A61K35/17 ,  C07K14/705 ,  C12N15/85 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  A01K67/00 ,  A61K39/00 ,  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：US10378026B2

公开(公告)日：2019-08-13

申请号：US14915434

申请日：2014-09-02

Applicant: CELLECTIS

Inventor： Andrew Scharenberg ,  Julianne Smith ,  Roman Galetto

IPC: C12N15/86 ,  C12N7/00

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.

公开(公告)号：US10286007B2

公开(公告)日：2019-05-14

申请号：US15659792

申请日：2017-07-26

Applicant: Cellectis

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

IPC: C12N15/63 ,  C12N5/00 ,  A61K35/17 ,  C12N5/0783 ,  C07K14/725 ,  C07K16/28 ,  C07K14/705 ,  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.