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

Front Immunol. 2023 Aug 9:14:1207276. doi: 10.3389/fimmu.2023.1207276. eCollection 2023.

Abstract

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.

Keywords: NK cell engager (NKCE); cancer; functionality; immunotherapy; manufacturability; natural killer (NK) cell.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • Humans
  • Immunity, Innate*
  • Immunotherapy
  • Killer Cells, Natural
  • Neoplasms* / therapy

Substances

  • Antibodies

Grants and funding

This work was supported by the National Research Foundation (NRF) Competitive Research Programme (CRP) grant (Grant No. CRP26-2021RS-0002) and the core fund of Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Singapore.