Leveraging CD16 fusion receptors to remodel the immune response for enhancing iPSC-derived NK cell anti-tumor immunotherapy

We developed a novel hnCD16FR construct that exhibit more potent cytotoxicity than reported hnCD16, which is a promising approach to treating hematologic malignancies and solid tumors with improved ADCC properties. We also offer a rationale for NK activation domains that remodel immune response to enhance CD16 signaling in NK cells. Overall design: To expand applications of hnCD16-mediated ADCC for NK-cell–based immunotherapy in cancer, we designed the ectodomain of hnCD16 fused with NK cell-specific activating domains in the cytoplasm (hnCD16 Fusion Receptor, FR), then transduced them to CD16-negative NK cell line and human iPSCs-derived NK (iNK) cells, and tested the function of several constructs in vitro and in vivo.