FT596 is an iPSC-derived, universal, off-the-shelf chimeric antigen receptor (CAR) NK cell immunotherapy for B-cell malignancy as a monotherapy and in combination with monoclonal antibody therapy such as rituximab. FT596 is created from a clonal master iPSC line engineered with the following features to enhance anti-tumor effector function:
- An NK cell-specific anti-CD19 CAR promotes enhanced cytotoxicity against CD19-expressing malignancies
- A high-affinity, non-cleavable CD16 Fc receptor promotes enhanced antibody-dependent cellular cytotoxicity (ADCC) when combined with therapeutic monoclonal antibodies
- A novel IL-15 receptor fusion enhances the persistence and expansion capabilities without requiring co-administration of cytokine support
In preclinical studies, FT596 has been shown to prevent tumor progression and to promote sustained long-term survival in a B-cell leukemia xenograft model. Moreover, as proof-of-concept for the mitigation of antigen escape, FT596 in combination with rituximab completely eliminates CD19+ and CD19- B-cell tumor cells in a co-culture cytotoxicity assay.
FT596 iPSC-Derived NK Cell Cancer Immunotherapy (2018 ASH)
Off-the-Shelf Natural Killer Cells with Multi-Functional Engineering Using a Novel Anti-CD19 Chimeric Antigen Receptor Combined with Stabilized CD16 and IL15 Expression to Enhance Directed Anti-Tumor Activity