Cellectis

Albert-ludwigs-universitat Freiburg

Agnes Gouble

Julianne Smith

Andrew M Scharenberg

Laurent Poirot

Roman Galetto

Stephanie Grosse

Cecile Mannioui

Philippe Duchateau

Cécile Schiffer-Mannioui

Andre Choulika

Jean-Charles Epinat

Jean-Pierre Cabaniols

David Sourdive

Emmanuel Lacroix

Frederic Paques

Toni Cathomen

Sylvain Arnould

Patrick Chames

Tatjana Cornu

Christophe Perez-Michaut

Claudio Mussolino

Marianna Romito

Sylvia Bruneau

Cécile Mannioui

Cecile Schiffer-Mannioui

Cécile Schiffer-mannioui

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.

Methods for engineering allogeneic and immunosuppressive resistant T cell for immunotherapy

The invention pertains to the field of cell therapy and HIV treatments. It provides with highly specific reagents for reducing or inactivating expression of CCR5 in primate and human primary cells, especially under the form of TALE-nucleases. These reagents allow the production of safer primary hematopoietic cells made resistant to HIV, stem cells or differentiated cells, for their infusion into HIV patients.

Sequence specific reagents targeting CCR5 in primary hematopoietic cells

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.

Use of pre T alpha or functional variant thereof for expanding TCR alpha deficient T cells

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.

Methods for engineering highly active T cell for immunotherapy

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.

Methods for engineering allogeneic and highly active t cell for immunotherapy

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.

Use of preTalpha or functional variant thereof for expanding TCRalpha deficient T cells

Methods for engineering allogeneic and immunosuppressive resistant T cell immunotherapy

An I-CreI variant, wherein one of the two I-CreI monomers has at least two substitutions, one in each of the two functional subdomains of the LAGLIDADG (SEQ ID NO: 150) core domain situated respectively from positions 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the mouse ROSA26 locus. Use of said variant and derived products for the engineering of transgenic mice and recombinant mouse cell lines expressing an heterologous protein of interest.

Meganuclease variants cleaving a DNA target sequence from the mouse ROSA26 locus and uses thereof

A single chain homing endonuclease, comprising a first variant of I-CreI having the amino acid sequence of accession number pdb 1g9y (SEQ ID NO: 23 is residues 1-153 of pdb Ig9y) and a second variant of I-CreI variant having the amino acid sequence of accession number pdb 1g9y (SEQ ID NO: 23 is residues 1-153 of pdb Ig9y) in a single polypeptide.

Use of meganucleases for inducing homologous recombination ex vivo and in toto in vertebrate somatic tissues and application thereof

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Paris, France

Agnes Gouble