Clinical Trials

Date: 2017-12-09

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at the 57th American Society of Hematology (ASH) Annual Meeting in Orlando9

Company: Fate Therapeutics (USA - CA)

Product: chimeric antigen receptor (CAR)-targeted CD8alphabeta+ T cells

Action mechanism:

• • immunotherapy product/cell therapy/gene therapy. Cellular immunotherapies are poised to transform the treatment of cancer and immunological conditions. However, cellular immunotherapies currently undergoing clinical investigation are patient-specific and their delivery requires the extraction, engineering, expansion and re-introduction of each individual patient's T cells. This multi-step manufacturing process is logistically challenging and complex, and significant hurdles remain to ensure that patient-specific T-cell immunotherapies can be efficiently and consistently manufactured, and safely and reliably delivered, at the scale necessary to support broad patient access and wide-spread commercialization.
• Induced pluripotent cells possess the unique dual properties of self-renewal and differentiation potential into all cell types of the body including T cells. Similar to master cell lines used for the manufacture of monoclonal antibodies, engineered pluripotent cell lines can repeatedly deliver clonal populations of T cells with broad histocompatibility and enhanced effector functions. These highly-stable pluripotent cell lines have the potential to serve as a renewable cell source for the consistent manufacture of homogeneous populations of effector cells for the treatment of many thousands of patients.
• In September 2016, Fate Therapeutics and Memorial Sloan Kettering Cancer Center launched a multi-year partnership led by Dr. Sadelain to develop off-the-shelf T-cell product candidates using clonal engineered MPCLs. The collaborators are currently conducting preclinical studies and finalizing current good manufacturing practice protocols for the development of CAR-targeted, TCR-null T-cell immunotherapies.
• In February 2017, Dr. Sadelain and colleagues published a set of preclinical studies in the journal Nature using primary T cells demonstrating that directing a CD19-specific CAR to the TRAC locus with CRISPR/Cas9 resulted in uniform CAR expression and enhanced T-cell potency as compared to conventional CAR T cells. Scientists from the laboratories of Sadelain and Fate Therapeutics advanced the observation by instead engineering iPSCs and generating CD8alphabeta+ T cells from a clonal engineered MPCL with a CD19-targeted CAR inserted into the TRAC locus and complete elimination of TCR expression. The collaborators demonstrated that the CAR-targeted, TCR-null CD8alphabeta+ T cells display antigen-specific anti-tumor potency, including cytokine release and targeted cellular cytotoxicity.

Disease:

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On December 9, 2017, Fate Therapeutics announced the generation of chimeric antigen receptor (CAR)-targeted CD8alphabeta+ T cells from a clonal engineered master pluripotent cell line (MPCL). The clonal engineered MPCL was created from an induced pluripotent stem cell (iPSC), which was modified in a one-time engineering event using CRISPR/Cas9 to both insert a CAR into the T-cell receptor - constant (TRAC) locus and eliminate T-cell receptor (TCR) expression. The groundbreaking development enables the renewable production of CAR-targeted, TCR-null CD8alphabeta+ T cells that are not restricted to an individual patient for off-the-shelf administration.
• The breakthrough was reported at the 59th American Society of Hematology Annual Meeting and Exposition by scientists from the laboratories of Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center and Fate Therapeutics.
• A first-in-human clinical trial of FT819, a CAR19 T-cell product candidate derived from a clonal engineered MPCL with complete elimination of TCR expression and TRAC-regulated CAR expression, is being planned.

Is general: Yes