Superiority of placenta-derived Natural Killer cells combined with Tri-Specific Engagers for cell therapy 4570

Abstract Description Cellular therapy using NK cells has shown exciting results against hematologic malignancies, but success in solid tumors has been limited. One limitation to successful solid tumor targeting may be the loss of CD16 in ex vivo activated and expanded NK cells since CD16 is a critical receptor for antibody-dependent cellular cytotoxicity. The human placenta represents a novel source of allogenic NK cells that may be harnessed for cell therapy. The goal of this study was to investigate placenta-derived NK (PL-NK) cells as an alternative and superior source of expanded NK cells compared to peripheral blood mononuclear cell-derived NK (PBMC-NK) cells. Lymphocytes from human placenta and PBMCs from human donors were obtained and co-cultured with irradiated K562.cl9mIL21 cells and IL-2. Resting and day 14 expanded cells underwent phenotypic analysis via flow cytometry and functional analysis by cytotoxicity assays. At rest, PL-NK cells exhibit higher expression of the activating receptor NKG2D. PL-NK cells demonstrated significantly higher expression of CD16 and CD69 compared to PBMC-NK cells along with significantly increased cytotoxicity against K562 target cells at 1:10 and 1:1 E:T ratios. Addition of B7-H3 tri-specific killer engager increased PL-NK cytotoxicity at all E:T ratios. These results suggest superiority of PL-NK cells over PBMC-NK cells and provide rationale for strategies using PL-NK cells with novel tri-specific engagers for ADCC enhancement against solid tumors. Funding Sources Suported by NIH/NCI R03CA252793, R03CA270854, U01CA224166, U01CA224166-02S1 Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)