公开(公告)号：US20200332004A1

公开(公告)日：2020-10-22

申请号：US16958250

申请日：2018-12-28

Applicant: CELLECTIS

Inventor： Alex BOYNE ,  Laurent POIROT ,  Philippe DUCHATEAU ,  Alexandre JUILLERAT

IPC: C07K16/28 ,  C12N5/0783 ,  C12N15/87 ,  C12N15/86 ,  A61K35/17 ,  A61P35/00

Abstract: A method for engineering less alloreactive immune cells, including T-cells that express chimeric antigen receptors (CARs), using a nucleotide sequence in form of an RNA encoding a anti-TCR CAR to achieve the transient expression of anti-TCR CAR at the cell surface. The transient expression of the anti-TCR CAR recognized by the alpha beta TCR on the cell surface unexpectedly enabled the a purification of the TCR-negative CAR expressing cells. The TCR-negative CAR expressing immune cells can be used in adoptive therapy to treat diseases associated with cell surface antigens, such as cancer with less side effects, in particular less GVHD.

公开(公告)号：US10765728B2

公开(公告)日：2020-09-08

申请号：US15302913

申请日：2015-04-10

Applicant: CELLECTIS

Inventor： Laurent Poirot ,  Mathieu Simon

IPC: A61K39/00 ,  C12N9/12 ,  C07K14/47 ,  A61K35/17 ,  C07K14/725

Abstract: The present invention pertains to engineered immune cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered immune cells of the present invention are characterized in that at least one gene selected from a gene encoding GCN2 and a gene encoding PRDM1 is inactivated or repressed. Such modified Immune cells are resistant to an arginine and/or tryptophan depleted microenvironment caused by, e.g., tumor cells, which makes the immune cells of the invention particularly suitable for immunotherapy. The invention opens the way to standard and affordable adoptive immunotherapy strategies using immune cells for treating different types of malignancies.

公开(公告)号：US10752684B2

公开(公告)日：2020-08-25

申请号：US15329932

申请日：2015-07-29

Applicant: Cellectis

Inventor： Cècile Schiffer-Mannioui

IPC: C07K16/28 ,  C07K16/30 ,  C07K14/705 ,  C07K14/725 ,  C12N5/0783 ,  A61K48/00 ,  A61K35/17 ,  C12N5/10 ,  C12N15/62 ,  A61K39/00 ,  C07K19/00

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 ROR1 monoclonal antibody, conferring specific immunity against ROR1 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia, and for solid tumors such as breast, colon, lung, and kidney tumors.

公开(公告)号：US20200157525A1

公开(公告)日：2020-05-21

申请号：US16664245

申请日：2019-10-25

Applicant: CELLECTIS

Inventor： Luc Mathis ,  Daniel F. Voytas ,  Feng Zhang ,  Benjamin Clasen ,  William Haun ,  Thomas Stoddard

IPC: C12N15/01 ,  C12N15/82

Abstract: Materials and methods are provided for making plants (e.g., Solanum varieties) with decreased accumulation of reducing sugars and acrylamide in cold-stored potatoes, specifically, by making TALE-nuclease-induced mutations in genes encoding vacuolar invertase.

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：US10301614B2

公开(公告)日：2019-05-28

申请号：US14387162

申请日：2013-03-15

Applicant: CELLECTIS, S.A.

Inventor： Philippe Duchateau ,  Julien Valton

IPC: C12N15/10 ,  G01N33/53 ,  C07K14/47 ,  C12N9/22

Abstract: The present invention relates to polypeptides and more particularly to Transcription Activator-Like Effector derived proteins that allow to efficiently target and/or process nucleic acids. Particularly, the present invention reports the characterization of TALE derived proteins that can efficiently target methylated DNA. The present invention more specifically relates to TALE derived proteins that allow activation of methylated promoters responsible for gene silencing.

公开(公告)号：US20180237798A1

公开(公告)日：2018-08-23

申请号：US15891496

申请日：2018-02-08

Applicant: Cellectis

Inventor： Philippe DUCHATEAU ,  Andre CHOULIKA ,  Laurent POIROT

IPC: C12N15/85 ,  C12N5/0783 ,  C12N9/22

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：US20180237533A1

公开(公告)日：2018-08-23

申请号：US15752195

申请日：2016-08-24

Applicant: CELLECTIS

Inventor： Alexandre JUILLERAT ,  Philippe DUCHATEAU ,  Laurent POIROT

IPC: C07K16/28 ,  A61K31/436 ,  A61K35/17 ,  C07K14/72 ,  A61P35/00

CPC classification number: C07K16/2869 ,  A61K31/436 ,  A61K35/17 ,  A61K38/00 ,  A61P35/00 ,  C07K14/7051 ,  C07K14/721 ,  C07K16/2803 ,  C07K2317/622 ,  C07K2319/03 ,  C12N2510/00

Abstract: The present invention relates to the field of cell immunotherapy and more particularly to a new generation of chimeric antigen receptors (CAR), allowing the control of immune cells endowed with such CARs through the interaction with small molecules. More particularly, the present invention relates to chimeric antigen receptor which comprise in at least one ectodomain a molecular switch turning the antigen binding function of the receptor from an off to on state, and vice versa. The present invention thus provides more controlled and potentially safer engineered CAR endowed immune cells, such as T-lymphocytes.

公开(公告)号：US20180236053A1

公开(公告)日：2018-08-23

申请号：US15751472

申请日：2016-07-26

Applicant: CELLECTIS

Inventor： Mathilde DUSSEAUX

IPC: A61K39/00 ,  A61K39/395 ,  C07K16/28 ,  C07K14/705 ,  A61P35/00

Abstract: Methods of developing genetically engineered immune cells for immunotherapy, which can be endowed with Chimeric Antigen Receptors targeting an antigen marker that is common to both the pathological cells and said CD38 immune by the fact that the genes encoding said markers are inactivated in said immune cells by a rare cutting endonuclease such as TALEN, Cas9 or argonaute.

公开(公告)号：US10006052B2

公开(公告)日：2018-06-26

申请号：US14891202

申请日：2014-05-28

Applicant: Cellectis ,  Precision Genome Engineering, Inc.

Inventor： Jordan Jarjour ,  Alexander Astrakhan

IPC: C12N15/90 ,  C12N9/22 ,  A61K35/17 ,  A61K38/46

CPC classification number: C12N15/907 ,  A61K35/17 ,  A61K38/465 ,  C12N9/22 ,  C12Y301/00

Abstract: Disclosed herein are compositions for inactivating the human CCR5 gene comprising engineered LAGLIDADG homing endonucleases (LHEs) and their derivatives, particularly derived from members of the \-Onul subfamily of LHE. Polynucleotides encoding such endonucleases, vectors comprising said polynucleotides, cells comprising or having been treated with such endonucleases, and therapeutic compositions deriving therefrom are also provided.