Date: 2015-07-16
Type of information: Publication of results in a medical journal
phase:
Announcement: publication of results in Cancer Research
Company: Cellectis (France)
Product: TALEN®-mediated genome editing
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Latest
news: * On July 16, 2015, Cellectis announced 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 (Multiplex genome edited T-cell manufacturing platform for \"off-the-shelf\" adoptive T-cell immunotherapies). 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.
