CAR T-cell therapy has recently emerged as a revolutionary and potentially curative therapy for patients with certain hematologic malignancies, including refractory cancers. In 2017, two CAR T-cell therapies were approved by the FDA for the treatment of relapsed / refractory B-cell precursor acute lymphoblastic leukemia (ALL) and relapsed / refractory diffuse large B-cell lymphoma (DLBCL). While most researchers and clinical investigators continue to focus on the development of autologous or donor-derived CAR T-cell therapies, we are developing CAR T-cell product candidates created from clonal master engineered iPSC lines as off-the-shelf cancer immunotherapies for the treatment of hematologic malignancies and solid tumors.
In September 2016, we announced a multi-year partnership with Memorial Sloan Kettering Cancer Center for the development of off-the-shelf engineered T-cell product candidates using clonal master iPSC lines and, in July 2019, we extended the partnership for an additional three years. Research and development activities under the collaboration are being led by Michel Sadelain, M.D., Ph.D., Director of the Center for Cell Engineering and the Stephen and Barbara Friedman Chair at Memorial Sloan Kettering Cancer Center at Memorial Sloan Kettering Cancer Center.
We are developing FT819, an off-the-shelf CAR T-cell cancer immunotherapy derived from a clonal engineered master iPSC line with a novel 1XX CAR targeting CD19 inserted into the T-cell receptor alpha constant (TRAC) locus and edited for elimination of T-cell receptor (TCR) expression. At the 2019 ASH Annual Meeting, we presented new in vivo preclinical data demonstrating that FT819 exhibits durable tumor control and extended survival. In a stringent xenograft model of disseminated lymphoblastic leukemia, FT819 demonstrated enhanced tumor clearance and control of leukemia as compared to primary CAR19 T cells. At Day 35 following administration, a bone marrow assessment showed that FT819 persisted and continued to demonstrate tumor clearance, whereas primary CAR T cells, while persisting, were not able to control tumor growth.
2022 ASH Poster PresentationInterim Phase I Clinical Data of FT819-101, a Study of the First-Ever, Off-the-Shelf, iPSC-Derived TCR-Less CD19 CAR T-Cell Therapy for Patients with Relapsed/Refractory B-Cell Malignancies
2021 ASH AbstractClinical Manufacture of FT819: Use of a Clonal Multiplexed-Engineered Master Induced Pluripotent Stem Cell Line to Mass Produce Off-the-Shelf CAR T-Cell Therapy
2019 ASH AbstractFT819: Translation of Off-the-Shelf TCR-Less Trac-1XX CAR-T Cells in Support of First-of-Kind Phase I Clinical Trial
Nature Medicine. 2019; 25: 82–88.Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency
FT819: Advanced B-Cell Malignancies
A Phase I Study of FT819 in Subjects With B-cell Malignancies (NHL, CLL, ALL)