Cellectis

Pfizer Corporation

Ecole Polytechnique Federale De Lausanne

Cellectis S.a.

New England Biolabs, Inc.

Allogene Therapeutics, Inc.

Epfl Ecole Polytechnique Fédérale De Lausanne

Alexandre Juillerat

Philippe Duchateau

Julien Valton

Claudia Bertonati

Laurent Poirot

Arvind Rajpal

Barbra Johnson Sasu

George H Silva

Kai Peter Johnsson

Jean-Charles Epinat

Thomas Charles Pertel

Roman Galetto

Thomas John Van Blarcom

Tracy Chia-Chien Kuo

Javier Fernando Chaparro Riggers

Maik Kindermann

Cesar Adolfo Sommer

Marine Beurdeley

Bijan Andre Boldajipour

Arnaud Gautier

Florent Beaufils

Julianne Smith

Donna Marie Stone

Brian Busser

Antje Keppler

Shobha Chowdary Potluri

Hughes Jaccard

Christian Heinis

Jan Barnikow

Thomas Gronemeyer

Christopher Chidley

George Silva

Kai Johnsson

The invention pertains to the field of adaptive cell immunotherapy. It provides with the genetic insertion of exogenous coding sequence(s) that help the immune cells to direct their immune response against infected or malignant cells. These exogenous coding sequences are more particularly inserted under the transcriptional control of endogenous gene promoters that are sensitive to immune cells activation. Such method allows the production of safer immune primary cells of higher therapeutic potential.

Targeted gene insertion for improved immune cells therapy

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. The present invention also concerns methods to use these proteins. The present invention also relates to vectors, compositions and kits in which RVD domains and Transcription Activator-Like Effector (TALE) proteins of the present invention are used.

Repeat variable diresidues for targeting nucleotides

The invention provides CARs (CARs) that specifically bind to BCMA (B-Cell Maturation Antigen). The invention further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The invention further relates to therapeutic methods for use of these CARs and engineered immune cells for the treatment of a condition associated with malignant cells expressing BCMA (e.g., cancer).

Chimeric antigen receptors targeting B-cell maturation antigen

The present invention relates to a method for the generation of compact Transcription Activator-Like Effector Nucleases (TALENS) that can efficiently target and process double-stranded DNA. More specifically, the present invention concerns a method for the creation of TALENs that consist of a single TALE DNA binding domain fused to at least one catalytic domain such that the active entity is composed of a single polypeptide chain for simple and efficient vectorization and does not require dimerization to target a specific single double-stranded DNA target sequence of interest and process DNA nearby the DNA target sequence. The present invention also relates to compact TALENs, vectors, compositions and kits used to implement the method.

Method for the generation of compact tale-nucleases and uses thereof

The present invention relates to new Transcription Activator-Like Effector proteins and more particularly new Transcription Activator-Like Effector Nucleases (TALENs) that can efficiently target and process nucleic acids. The present invention also concerns methods to use these new Transcription Activator-Like Effector proteins. The present invention also relates to vectors, compositions and kits in which Transcription Activator-Like Effector proteins of the present invention are used.

Tale-protein scaffolds and uses thereof

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 TXYXXX, wherein Xis an amino acid Xis an amino acid Xis an amino acid and Xis V or I.

Inhibitory chimeric antigen receptors

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward CLL1 positive cells. The engineered immune cells endowed with such CARs are particularly suited for immunotherapy for treating cancer, in particular leukemia.

Anti-CLL1 specific single-chain chimeric antigen receptors (scCARs) for cancer immunotherapy

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.

Chimeric antigen receptors with integrated controllable functions

The present invention relates to Transcription Activator-Like Effector (TALE) derived proteins that allow efficient targeting and/or processing of double stranded nucleic acid sequences. The proteins of the invention are typically chimeric protein monomers composed of a core scaffold comprising Repeat Variable Dipeptide regions (RVDs) having binding specificity to a DNA target sequence, to which is fused a catalytic domain to its N-terminus. This later catalytic domain, which can be a monomer of a nuclease, is placed at this position to possibly interact with another catalytic domain fused to another TAL monomer, such that, when the monomers are binding to their respective target DNA sequences, both catalytic domains form a catalytic entity likely to process DNA in the proximity of these target sequences. This new TAL architecture makes it possible to target only one DNA strand, which is not the case, for instance, with classical TALEN architectures. The present invention also relates to vectors encoding such proteins and compositions or kits in which Transcription Activator-Like Effector (TALE) proteins of the present invention are used.

Transcription activator-like effector (TALE) fusion protein

The present invention is in the field of genetic editing tools and methods of genetic engineering. It relates to the engineering of rare-cutting endonucleases designed to contract highly repetitive motives in chromosomes, which are at the origin of certain genetic diseases, in particular the so-called 'triplet repeat diseases', such as the Huntington disease. The invention encompasses the method for contracting the repetitive motives, the rare-cutting endonucleases for use to contract repetitive motives in a gene subjected to repeat disorder, the polynucleotides and vectors encoding thereof as well as the resulting pharmaceutical compositions.

Rare-cutting endonucleases for efficient and specific targeting DNA sequences comprising highly repetitive motives

The present invention relates to a method to modulate the level of activation of an engineered immune cell (such as a Chimeric Antigen Receptor T-cell) for immunotherapy. The present invention also relates to cells obtained by the present method, preferably comprising said modulable/tunable chimeric antigen receptors for use in therapeutic or prophylactic treatment.

Method for modulating car-induced immune cells activity

The present invention concerns new modular base-per-base specific nucleic acid binding domains (MBBBD) derived from newly identified proteins from the bacterial endosymbiontand their use for engineering nucleic acid processing enzymes, such as specific endonucleases or transcription activators.

Modular base-specific nucleic acid binding domains from burkholderia rhizoxinica proteins

Methods for improving or modulating targeting specificity of TALE proteins by introducing alternative RVDs into their modular nucleic acid binding domains. Polynucleotides encoding TALE proteins having alternative targeting specificity towards a nucleic acid target sequence. TALE proteins having alternative targeting specificity towards a nucleic acid target sequence and methods of making and using them.

Methods for modulating TAL specificity

The present invention relates to a method to engineer immune cell for immunotherapy. In particular said immune cells are engineered with chimeric antigen receptors, which be activated by the combination of hypoxia and ligand extracellular binding as input signals. The invention also relates to new designed chimeric antigen receptors which are able to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties and the hypoxia condition. The present invention also relates to cells obtained by the present method, in particular T-cells, comprising said chimeric antigen receptors for use in cancer treatments.

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Paris, France

Alexandre Juillerat