T-cell 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.
Engineering therapeutic attributes into master iPSC lines, such as antigen specificity, lack of alloreactivity, enhanced persistence and histocompatibility, is a breakthrough approach to renewably generate potent T-cell immunotherapies. This unique approach offers the prospect for off-the-shelf delivery of T-cell immunotherapies with enhanced safety and therapeutic potential at the scale necessary to treat significant numbers of patients.
Fate’s lead CAR iT program, FT819, is an off-the-shelf CAR-T cell therapy that is manufactured from a clonal master iPSC line. This line is engineered to completely eliminate expression of the T-cell receptor and preferentially regulate CAR19 expression by inserting the CAR into the T-cell receptor constant (TRAC) locus. In preclinical studies, FT819 exhibits a target-specific T-cell response in vitro when challenged with CD19-positive tumor cells and displays enhanced production of effector cytokines and cytolytic proteins.
Currently, Fate is conducting additional preclinical and IND-enabling activities for FT819. In addition to FT819, Fate is conducting research on additional CAR iT product candidates engineered with additional features to address important considerations such as the tumor microenvironment and antigen escape with the goal of enabling a portfolio of off-the-shelf, best-in-class CAR-T products.
Fate Therapeutics has exclusively licensed from Memorial Sloan Kettering (MSK) intellectual property covering the production and composition of iPSC-derived T cells for human therapeutic use. In May 2018, Fate and MSK expanded their relationship, with Fate gaining access to additional intellectual property from MSK that enables the development of gene-edited T-cell immunotherapies. The newly-licensed portfolio of intellectual property covers new chimeric antigen receptor (CAR) constructs as well as off-the-shelf CAR T cells, including the use of CRISPR and other innovative technologies for their production.