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Updated: Aug 7, 2026
Artificial Antigen Presenting Cell (aAPC) Mediated Activation and Expansion of Natural Killer T Cells
Published on: December 29, 2012
CD16 polymorphisms and NK activation induced by monoclonal antibody-coated target cells
Julie A Bowles1, George J Weiner
15970 JPP, Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, United States.
Abstract:
CD16 and natural killer (NK) cells appear to play a central role in mediating the anti-tumor effects of monoclonal antibody (mAb) therapy, yet little is known about changes in NK cells that result from interaction of the NK cells with mAb-coated tumor cells under physiologic conditions. We developed a system using peripheral blood mononuclear cells (PBMCs) and either transformed B cells or breast cancer cells to assess how mAbs impact on NK cell phenotype. Rituximab, apolizumab and trastuzumab induced modulation of CD16 and upregulation of CD54 on NK cells when the appropriate target cells were present. Higher concentrations of mAb were needed to induce these changes on NK cells from subjects with the lower affinity CD16 polymorphism. Phenotypic changes were greater in NK cells from subjects with the higher affinity polymorphism even when saturating concentrations of mAb were used, demonstrating increased concentration of mAb can overcome some, but not all, of the influence CD16 polymorphisms have on NK activation. These studies provide a straightforward and easily reproducible technique to measure the ability of mAb-coated tumor cells to activate NK cells in vitro which should be particularly useful as mAbs with varying affinity for both target antigen and Fc receptor (FcR) are developed.
Insights
Monoclonal antibody (mAb) therapy efficacy in cancer relies on natural killer (NK) cells. This study reveals how NK cells change when interacting with mAb-coated tumor cells, impacting treatment effectiveness.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Natural killer (NK) cells and CD16 are crucial for monoclonal antibody (mAb) therapy's anti-tumor effects.
- Limited understanding exists regarding NK cell alterations upon interaction with mAb-coated tumor cells under physiological conditions.
Purpose of the Study:
- To investigate the impact of mAbs on NK cell phenotype through interaction with mAb-coated tumor cells.
- To establish a reproducible system for assessing NK cell activation by mAb-coated tumor cells.
Main Methods:
- Utilized peripheral blood mononuclear cells (PBMCs) co-cultured with transformed B cells or breast cancer cells.
- Assessed phenotypic changes in NK cells, including CD16 modulation and CD54 upregulation, in response to specific mAbs (Rituximab, apolizumab, trastuzumab).
- Evaluated the influence of CD16 polymorphisms (high-affinity vs. low-affinity) on NK cell responses to varying mAb concentrations.
Main Results:
- Rituximab, apolizumab, and trastuzumab induced CD16 modulation and CD54 upregulation on NK cells when appropriate target cells were present.
- Higher mAb concentrations were required to elicit these changes in individuals with low-affinity CD16 polymorphisms.
- NK cells from individuals with high-affinity CD16 polymorphisms exhibited greater phenotypic changes, even at saturating mAb concentrations, indicating partial overcoming of polymorphism influence by mAb concentration.
Conclusions:
- Developed a straightforward in vitro system to measure NK cell activation by mAb-coated tumor cells.
- NK cell activation is influenced by both mAb concentration and CD16 polymorphisms.
- This method is valuable for developing future mAbs with tailored Fc receptor affinities for enhanced anti-tumor activity.
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