In addition to CD38 targeting in multiple myeloma, targeting of other tumor-associated cell-surface proteins has been clinically investigated. Of these antigens, the TNF-superfamily member B-cell Maturation Antigen (BCMA) is among the most researched. Several clinical trials in multiple myeloma have shown promising initial results targeting BCMA with CAR T cells.
We are developing FT576, an investigational, universal, off-the-shelf NK cell cancer immunotherapy derived from a clonal master iPSC line. FT576 incorporates four functional modifications: a proprietary CAR that targets BCMA; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to augment ADCC; an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity; and the elimination of CD38 expression to mitigate the potential for NK cell fratricide. Together, these features are intended to enable multi-antigen targeting of myeloma cells, augment ADCC, enhance cell persistence and prevent anti-CD38 monoclonal antibody-induced fratricide.