Model FT536 - Solid and Hematopoietic Tumor Cells
MICA and MICB (MICA/B) are stress proteins expressed on a broad range of solid and hematopoietic tumor cells and serve as an activation signal for NKG2D+ NK and T cells. However, MICA/B are frequently shed as an immune escape mechanism, preventing recognition and destruction of tumor cells by the immune system. Proteolytic shedding of MICA/B can be inhibited by monoclonal antibodies targeting the membrane proximal α3 domain, which stabilizes MICA/B on the cell surface.
Details
We are developing FT536, an investigational, universal, off-the-shelf NK cell cancer immunotherapy derived from a clonal master engineered iPSC line. FT536 incorporates four functional modifications: a proprietary CAR that targets the α3 domain of MICA and MICB; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor that augments ADCC; an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity; and the elimination of CD38 expression which enhances NK cell metabolic fitness, persistence and anti-tumor functionality.
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