A novel off‐the‐shelf trastuzumab‐armed NK cell therapy (ACE1702) using antibody‐cell‐conjugation technology

Abstract

Natural killer (NK) cells harbor efficient cytotoxicity against tumor cells without causing life‐threatening cytokine release syndrome (CRS) or graft‐versus‐host disease (GvHD). When compared to chimeric antigen receptor (CAR) technology, Antibody‐Cell Conjugation (ACC) technology has been developed to provide an efficient platform to arm immune cells with cancer‐targeting antibodies to recognize and attack cancer cells. Recently, we established an endogenous CD16‐ex-pressing oNK cell line (oNK) with a favorable expression pattern of NK activation/inhibitory recep-tors. In this study, we applied ACC platform to conjugate oNK with trastuzumab and an anti‐hu-man epidermal growth factor receptor 2 (HER2) antibody. Trastuzumab‐conjugated oNK, ACE-oNK‐HER2, executed in vitro and in vivo cytotoxicity against HER2‐expressing cancer cells and showed enhanced T cell‐recruiting capability and secretion of IFNγ. The irradiated and cryo-preserved ACE‐oNK‐HER2, designated as ACE1702, retained superior HER2‐specific in vitro and in vivo potency with no tumorigenic potential. In conclusion, this study provides the evidence to support the potential clinical application of ACE1702 as a novel off‐the‐shelf NK cell therapy against HER2‐expressing solid tumors.