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Cellectis demonstrates fine & predictable tuning of TALEN gene editing targeting to improve T-cell adoptive immunotherapy

New York
Wednesday, November 22, 2017, 15:00 Hrs  [IST]

Cellectis, a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), announced the publication of a study in Molecular Therapy — Nucleic Acids describing the educated engineering of highly specific and efficient TAL nucleases (TALEN) targeting PD1, a key T-cell immune checkpoint.

In this report, Anne-Sophie Gautron, Ph.D., Alexandre Juillerat, Ph.D., and their collaborators used a strategy developed by Cellectis to control TALEN targeting based on a proprietary technology leveraging the exclusion capacities of non-conventional RVDs. This approach allows combined disruptions of the desired TRAC and PDCD1 loci by TALEN while eliminating low frequency off-site processing. By adjusting a few RVDs, they provided a rapid and straightforward redesign of optimal TALEN combinations for multiplex gene editing. This approach can greatly benefit gene editing for therapeutic applications where high editing efficiencies need to be associated with maximal specificity and safety.

Dr. Anne-Sophie Gautron, Ph.D., graduated in immunology from the University Pierre et Marie Curie/Pasteur Institute, Paris 6, France. After receiving her Ph.D. in immunology in 2009 from the University René Descartes, Paris 5, France, she joined the Neurology and Immunobiology departments at Yale University, Connecticut, where she studied the role of regulatory T-cells in inhibiting pathogenic Th1 and Th17-cell responses. In 2014, she joined the Early Discovery team of Cellectis in Paris, France, working on the development of the next generation of CAR T-cells for adoptive immunotherapy. In 2017, she joined the CAR development group to lead projects associated with the development of new CAR-expressing engineered T-cells for administration as “off-the-shelf” immunopharmaceuticals for cancer treatment.

Dr. Alexandre Juillerat, Ph.D., graduated in Chemistry from the University of Lausanne, Switzerland. After receiving in 2006 his Ph.D. in protein engineering from the École Polytechnique Fédérale de Lausanne (EPFL, Switzerland), he moved to the laboratory of Structural Immunology at the Institut Pasteur in Paris, France, performing structure-function studies on a major adhesin of plasmodium falciparum. In 2010, he joined the R&D department of Cellectis in Paris, France, working on the development and implementation of sequence specific designer nucleases including the transcription activator-like effector nucleases TALEN. He then joined the Cellectis facility based in New York, NY, USA, leading projects associated with the development of the T-cell chimeric antigen receptor (CAR) technology.

 

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