Our lead iPSC-derived cancer immunotherapy program is a targeted NK cell therapy product created from a master engineered iPSC line expressing a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor. Our novel hnCD16 Fc receptor has been modified to augment its binding affinity to monoclonal antibodies and to prevent the receptor’s shedding from the surface of NK cells upon activation, which can otherwise diminish the cells’ anti-tumor activity.
Engineered high-Affinity non-Cleavable CD16 Fc Receptor
In preclinical studies, we have shown that our hnCD16-iNK cell therapy product exhibits potent and persistent anti-tumor activity in multiple tumor cell recognition and killing assays:
- hnCD16-iNK cells augment anti-tumor activity in combination with trastuzumab (brand name Herceptin) in vivo, as compared to mice treated with trastuzumab alone, in a HER2+ ovarian cancer model;
- hnCD16-iNK cells exhibit superior ADCC when combined with cetuximab (brand name Erbitux), as compared to conventional NK cells sourced from peripheral blood and cord blood, in an in vitro killing assay of a human ovarian cancer cell line; and
- hnCD16-iNK cells show a dose-dependent killing response in combination with rituximab (brand name Rituxan) in vitro in a CD20+ human lymphoblast-derived B-lymphocyte cell line killing assay.