On July 16, 2015 Cellectis reported the publication of a study in Cancer Research describing the applicability of TALEN-mediated genome editing to a scalable process, which enables the manufacturing of third-party CAR T-cell immunotherapies (Filing, 6-K, Cellectis, JUL 16, 2015, View Source [SID:1234506351]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Adoptive immunotherapy using autologous T-cells endowed with chimeric antigen receptors or CARs has emerged as a powerful means of treating cancer. However, a limitation of this approach is that autologous CAR T-cells must be generated on a custom-made basis.
To overcome the limitations of patient-derived CAR T-cell therapies, TALEN mediated gene inactivation can be used to generate non-alloreactive T-cells from third-party donors in a robust, scalable manufacturing process, thus allowing "off-the-shelf" CAR T-cell immunotherapies.
Laurent Poirot Ph.D. and his collaborators use this TALEN-mediated editing approach to develop a process for the large-scale manufacturing of T-cells deficient in expression of both their T-cell receptor (TCR) and CD52, a protein targeted by alemtuzumab, a chemotherapeutic agent. Functionally, T-cells manufactured with this process do not mediate graft-versus-host reactions, and are rendered resistant to destruction by alemtuzumab. These characteristics enable the administration of alemtuzumab concurrently or prior to engineered T-cells, supporting their engraftment.
Furthermore, endowing the TALEN-engineered cells with a CD19 CAR led to efficient destruction of CD19+ tumor targets even in the presence of the chemotherapeutic agent.
CAR T-cell immunotherapies can therefore be used in an "off-the-shelf" manner akin to other biological immunopharmaceuticals.
Laurent Poirot, Ph.D., Head of Early Discovery
Dr. Laurent Poirot studied physics and biology at the Ecole Polytechnique in France, before earning his Ph.D. at the Strasbourg University (France) and the Harvard Medical School in Boston. He then joined the Genomics Institute of the Novartis research foundation in San Diego as a postdoctoral fellow, where he studied the development of high throughput in vivo and in vitro approaches for the study of gene functions in immune cells. He joined Cellectis in 2009 as a Project Leader, and has been working as Head of Early Discovery since 2013.
Multiplex genome edited T-cell manufacturing platform for "off-the-shelf" adoptive T-cell immunotherapies
Laurent Poirot1, Brian Philip2, Cécile Schiffer Mannioui1, Diane Le Clerre1, Isabelle Chion-Sotinel1, Sophie Derniame1, Pierrick Potrel1, Cécile Bas1, Laetitia Lemaire1, Roman Galetto1, Céline Lebuhotel1, Justin Eyquem1,3, Gordon Weng-Kit Cheung2, Aymeric Duclert1, Agnès Gouble1, Sylvain Arnould1, Karl Peggs2, Martin Pule2, Andrew M. Scharenberg4 and Julianne Smith1
1 Cellectis, Paris, France
2 Department of Haematology, UCL Cancer Institute, University College London, London, UK
3 Current address: Memorial Sloan-Kettering Cancer Center, New York, NY
4 Current address: Department of Pediatrics, University of Washington, Seattle Children’s Research Institute, Seattle, WA