Preferred Label : iPSC-derived CD16/IL-15RF-expressing CD38-eliminated NK Cells FT538;
NCIt synonyms : Induced Pluripotent Stem Cell-derived CD16/IL-15RF-expressing CD38-eliminated Natural
Killer Cells FT538;
NCIt definition : An allogeneic, off-the-shelf, natural killer (NK) cell product derived from a clonal
master induced pluripotent stem cell (iPSC) line, and engineered and CRISPR-edited
to express a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor and a recombinant
fusion of IL-15 and IL-15 receptor alpha (IL-15RF), and to eliminate CD38 expression,
with potential immunostimulatory and antineoplastic activities. Upon administration,
iPSC-derived CD16/IL-15RF-expressing CD38-eliminated NK cells FT538 bind to stress-induced
ligands on tumor cells, leading to tumor cell lysis and release of tumor neoantigens.
Additionally, FT538 NK cells secrete inflammatory cytokines and chemokines, thereby
enhancing T-cell activity and recruitment to the tumor site. IL-15RF promotes the
survival of NK cells and enhances the cytotoxic effect of the NK cells and the activated
anti-tumor T-cells. When used in combination with monoclonal antibodies, the hnCD16
Fc receptor of FT538 binds to the Fc portion of tumor cell-bound monoclonal antibodies,
leading to NK cell activation, cytokine secretion and enhanced antibody-dependent
cellular cytotoxicity (ADCC). CD16, also known as Fc-gamma receptor III, is normally
expressed on the surface of NK cells, neutrophils, monocytes and macrophages, and
plays a key role in initiating ADCC. It is often downregulated in certain cancers,
thereby inhibiting the anti-tumor immune response. The lack of CD38 in FT538 NK cells
prevents NK cell fratricide upon co-administration with a CD38-targeting monoclonal
antibody as CD38 is normally expressed on the surface of activated NK cells. This
enhances ADCC mediated by CD38-targeting monoclonal antibodies.;
Molecule name : FT-538; FT 538;
NCI Metathesaurus CUI : CL1642672;
Origin ID : C176623;
UMLS CUI : C5447330;
Semantic type(s)
- Cell [UMLS semantic type]
- concept_is_in_subset
