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.

公开(公告)号：US20190216853A1

公开(公告)日：2019-07-18

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: A61K35/17 ,  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：US20190209616A1

公开(公告)日：2019-07-11

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

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 ,  C07K2319/02 ,  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.

公开(公告)号：US20190002573A1

公开(公告)日：2019-01-03

申请号：US15925182

申请日：2018-03-19

Applicant: CELLECTIS

Inventor： Roman GALETTO

IPC: C07K16/28 ,  C07K14/725 ,  A61K39/00

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 CD123 monoclonal antibody, conferring specific immunity against CD123 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia.

公开(公告)号：US20180171298A1

公开(公告)日：2018-06-21

申请号：US15578946

申请日：2016-06-30

Applicant: Cellectis

Inventor： Philippe DUCHATEAU ,  Jean-Pierre CABANIOLS ,  Julien VALTON

IPC: C12N5/0783 ,  C12N15/63 ,  A61K35/17 ,  A61K45/06 ,  C12N9/22 ,  C07K14/47 ,  C07K14/725 ,  C12N9/12

CPC classification number: C12N5/0646 ,  A61K35/17 ,  A61K45/06 ,  A61K2039/515 ,  A61K2039/572 ,  C07K14/4703 ,  C07K14/7051 ,  C12N9/12 ,  C12N9/22 ,  C12N15/63 ,  C12N2510/00

Abstract: The present invention relates to methods for improving therapeutic activity of NK cell, such as their cytotoxic/cytolytic activity, to be used in immunotherapy, by gene editing. In particular, these methods comprise a step of reduction or inactivation of gene expression using specific endonuclease such as TAL-nuclease, CRISPR or Argonaute. An additional genetic modification can be performed by (over)expressing at least one gene involved in N K function. The present invention encompasses also engineered NK cell, pharmaceutical composition containing the same.

公开(公告)号：US20180051089A1

公开(公告)日：2018-02-22

申请号：US15546623

申请日：2016-01-25

Applicant: Cellectis

Inventor： Roman GALETTO ,  Barbara Johnson SASU ,  Arvind RAJPAL ,  Philippe DUCHATEAU ,  Alexandre JUILLERAT ,  Julien VALTON ,  Mathieu SIMON

IPC: C07K16/28 ,  A61K35/17 ,  A61K39/00 ,  C07K14/725 ,  C07K16/30 ,  C12N5/00 ,  C12N5/0783

CPC classification number: C07K16/2866 ,  A61K35/17 ,  A61K39/0011 ,  A61K39/39558 ,  A61K2039/505 ,  A61K2039/5156 ,  A61K2039/5158 ,  A61K2039/6056 ,  A61K2039/64 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70535 ,  C07K14/70578 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/3061 ,  C07K2317/24 ,  C07K2317/53 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/03 ,  C12N5/0093 ,  C12N5/0636 ,  C12N5/0638 ,  C12N2510/00 ,  G01N15/1031 ,  G01N15/14 ,  G01N2015/008 ,  G01N2015/1006 ,  G01N2015/1081 ,  G01N2015/149

Abstract: The present invention relates to a TCR KO—or TCR KO and dCK KO—engineered immune cells expressing a Chimeric Antigen Receptors (CAR) specific for CD123 that is a recombinant chimeric protein able to redirect immune cell specificity and reactivity toward CD123-expressing cells, and more particularly in which extracellular ligand binding is a scFV derived from a CD123 monoclonal antibody, conferring specific immunity against CD123 positive cells. The engineered immune cells endowed with such CD123 CARs are particularly suited for treating relapse refractory AML and blastic plasmacytoid dendritic cell neoplasm and for use as a treatment before bone marrow transplantation.

公开(公告)号：US20180044399A1

公开(公告)日：2018-02-15

申请号：US15525906

申请日：2015-11-09

Applicant: RINAT NEUROSCIENCE CORP. ,  CELLECTIS

Inventor： Arvind RAJPAL ,  Shobha Chowdary POTLURI ,  Laurent POIROT ,  Alexandre JUILLERAT ,  Thomas Charles PERTEL ,  Donna Marie STONE ,  Barbra Johnson SASU

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

CPC classification number: C07K14/70503 ,  A61K35/17 ,  A61K2039/5156 ,  C07K14/7051 ,  C07K14/70517 ,  C07K14/70521 ,  C07K14/70578 ,  C07K16/2803 ,  C07K16/3069 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2319/03 ,  C07K2319/70 ,  C07K2319/74 ,  C12N5/0636 ,  C12N2510/00

Abstract: The invention relates to an inhibitory chimeric antigen receptor (N-CAR) comprising an extracellular domain comprising an antigen binding domain, a transmembrane domain, and, an intracellular domain wherein the intracellular domain comprises an Immunoreceptor Tyrosine-based Switch Motif ITSM, wherein said ITSM is a sequence of amino acid TX1YX2X3X4, wherein X1 is an amino acid X2 is an amino acid X3 is an amino acid and X4 is V or

公开(公告)号：US09855297B2

公开(公告)日：2018-01-02

申请号：US15045368

申请日：2016-02-17

Applicant: Cellectis

Inventor： Philippe Duchateau ,  André Choulika ,  Laurent Poirot

IPC: C12N5/00 ,  A61K35/17 ,  C12N5/0783 ,  C12N9/22 ,  C12N15/90

CPC classification number: C12N15/85 ,  A61K35/17 ,  C12N5/0636 ,  C12N5/0637 ,  C12N5/0638 ,  C12N9/22 ,  C12N15/1138 ,  C12N15/90 ,  C12N2310/20 ,  C12N2510/00 ,  C12Y301/00

Abstract: The present invention relates to methods of developing genetically engineered, preferably non-alloreactive T-cells for immunotherapy. This method involves the use of RNA-guided endonucleases, in particular Cas9/CRISPR system, to specifically target a selection of key genes in T-cells. The engineered T-cells are also intended to express chimeric antigen receptors (CAR) to redirect their immune activity towards malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies using T-Cells for treating cancer and viral infections.

公开(公告)号：US20170360835A1

公开(公告)日：2017-12-21

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: A61K35/17 ,  C07K16/28 ,  C12N5/0783 ,  C07K14/725 ,  C07K14/705 ,  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: 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：US20170226183A1

公开(公告)日：2017-08-10

申请号：US15329530

申请日：2015-07-29

Applicant: CELLECTIS

Inventor： Cècile SCHIFFER-MANNIOUI

IPC: C07K14/735 ,  C07K16/28

CPC classification number: C07K14/70535 ,  C07K16/2803 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/03 ,  C07K2319/33 ,  C07K2319/70

Abstract: The present invention relates to a new generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs, which are made specific to the antigen ROR1. Such CARs aim to redirect immune cell specificity and reactivity toward malignant cells expressing the tumor antigen ROR1. The alpha, beta and gamma polypeptides composing these CARs 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, especially chronic lymphocytic leukemia or solid tumors.