On June 25, 2020 Cellectis (Euronext Growth: ALCLS; Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported the publication of a new research paper released today in Frontiers in Bioengineering and Biotechnology (Press release, Cellectis, JUN 25, 2020, View Source [SID1234561477]). This article describes an innovative and easy-to-implement procedure which will streamline the manufacturing of allogeneic ‘off-the-shelf’ CAR T-cell therapies.
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The methodology described in this article defines a novel non-mechanical purification strategy to generate TCRαβ negative (allogeneic) cells for CAR T-cell therapies. With an early and transient expression of an anti-CD3 CAR in the engineered donor T-cells, Cellectis programed these cells to self-eliminate the remaining TCR+ cell population and obtained an ultrapure TCRαβ(-) population (up to 99.9%) at the end of the CAR-T production.
"We propose a novel, modular and broadly implementable methodology that can efficiently eliminate residual TCRαβ+ cells during the early steps of the allogeneic CAR T-cell generation process without altering key characteristics (T-cell differentiation, exhaustion markers, proliferative capacity and target cell killing capacity)", said Alexandre Juillerat, Ph.D., Team Leader, Innovation Department and NY Laboratory Head, Cellectis. "This study provides a proof of concept to produce the next generation of allogeneic ‘off-the-shelf’ CAR T-cell therapies," he added.
Using Cellectis’ proprietary technologies, TALEN gene editing together with our PulseAgile cell electroporation device, the innovation team developed a new strategy to achieve purification levels compatible with manufacturing and clinical requirements, including the prevention of GvHD. This new method offers optimal outcome for potential future applications in both liquid and solid tumor development programs.
Alexandre Juillerat, Ph.D., Team Leader, Innovation Department and NY Laboratory Head, Cellectis
Alexandre Juillerat, Ph.D., graduated in Chemistry from the University of Lausanne, Switzerland. After receiving his Ph.D. in 2006 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. 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, leading projects associated with the development of the T-cell chimeric antigen receptor (CAR) technology. Cellectis’ New-York-based innovation team is constantly at the forefront of pioneered research, inventing and generating robust, first-in-class allogeneic CAR T-cell product candidates that address multiple unmet cancer needs.