Genetically engineered T cells are at the forefront of an emerging wave of breakthrough scientific research focused on harnessing the power of the immune system to treat cancer and other immune disorders. Progress to date has been encouraging, however several important considerations must be addressed to unlock the full potential of this new modality across a much broader range of patients.
These considerations include:
- Efficacy and safety across a broader range of patients, enabled by cells engineered with the optimal features;
- Off-the-shelf product administration for more timely and accessible treatment; and
- Scalable, consistent, and cost-effective manufacturing of the drug product.
To address these considerations, Fate has established an innovative platform for deriving chimeric antigen receptor (CAR)-T and other cell therapies from induced pluripotent stem cells (iPSCs). Fate’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event, and selecting a single iPSC with the desired genetic composition for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be consistently and repeatedly produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf to treat many patients.
Using this platform, we are developing CAR T-cell products created from master engineered iPSC lines as off-the-shelf cancer immunotherapies for the treatment of liquid and solid tumors. 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 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 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 obtaining rights to additional intellectual property from MSK for the development of gene-edited T-cell immunotherapies. The newly-licensed portfolio of intellectual property covers new CAR constructs as well as off-the-shelf CAR T cells, including the use of CRISPR and other innovative technologies for their production.