Title:Antibody-Dependent Cell-Mediated Cytotoxicity Through Natural Killer
(NK) Cells: Unlocking NK Cells for Future Immunotherapy
Volume: 23
Issue: 4
Author(s): Ding Sheng Chin, Crystale Siew Ying Lim, Fazlina Nordin, Norsyahida Arifin and Tye Gee Jun*
Affiliation:
- Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Minden, Penang, Malaysiaa
Keywords:
Natural killer cell, antibody-dependent cellular cytotoxicity, Fc receptor, CD16, therapeutic antibodies, immunotherapy.
Abstract: Background: Natural killer (NK) cells have potent effector functions that can be further improved
for therapeutic purposes through antibody-dependent cell-mediated cytotoxicity (ADCC). Specific
killing of virus-infected cells and cancer cells is modulated through target specific antibodies that subsequently
recruit NK cells for ADCC. NK cells produce cytokines similar to activated T cells, but is less
persistent as NK cells have short-lived responses. These features benefit the development of customisable
and more individualised cell-based therapies.
Objectives: Preclinical studies with NK cells were promising and several clinical studies are ongoing to
investigate their use in antibody therapies. However, more reliable ADCC assays are required for evaluating
NK cell activity to optimise therapeutic antibodies. The therapeutic potential of NK cell therapy could
then be improved by harnessing ADCC.
Methods: This review discusses recent studies on key components of NK cell-mediated ADCC, current
clinical trials involving NK cells, ADCC assay developments and various techniques to improve ADCC.
Results: Improvements can be made to NK-mediated ADCC through modifications of antibodies, effector
cells and target antigens. Different aspects of antibodies were studied extensively, including modifying
glycosylation patterns, novel production methods, combination regiments, bispecific antibodies, and conjugated
antibodies. Modification of NK cells and tumour surface markers could improve ADCC of even
treatment-resistant cancer cells. Additives such as cytokines and other immunomodulatory agents can further
augment ADCC to supplement NK cell-based therapies.
Conclusion: ADCC improvements could be incorporated with current biological techniques such as
adoptive transfer of NK cells and chimeric antigen receptor (CAR) NK cells, to improve the outcome of
NK cell-based therapy and pave the way for future immunotherapies.