Natural Killer Cell Engagers (NKCEs): a new frontier in cancer immunotherapy

• Published in: Frontiers in immunology Vol. 14; p. 1207276
• Main Authors: Zhang, Minchuan, Lam, Kong-Peng, Xu, Shengli
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 09.08.2023
• Subjects: cancer; functionality; Immunology; immunotherapy; manufacturability; natural killer (NK) cell; NK cell engager (NKCE)
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1207276

Natural Killer (NK) cells are a type of innate lymphoid cells that play a crucial role in immunity by killing virally infected or tumor cells and secreting cytokines and chemokines. NK cell-mediated immunotherapy has emerged as a promising approach for cancer treatment due to its safety and effectiveness. NK cell engagers (NKCEs), such as BiKE (bispecific killer cell engager) or TriKE (trispecific killer cell engager), are a novel class of antibody-based therapeutics that exhibit several advantages over other cancer immunotherapies harnessing NK cells. By bridging NK and tumor cells, NKCEs activate NK cells and lead to tumor cell lysis. A growing number of NKCEs are currently undergoing development, with some already in clinical trials. However, there is a need for more comprehensive studies to determine how the molecular design of NKCEs affects their functionality and manufacturability, which are crucial for their development as off-the-shelf drugs for cancer treatment. In this review, we summarize current knowledge on NKCE development and discuss critical factors required for the production of effective NKCEs.