CD16A is a potent cytotoxicity receptor on human NK cells, which can be exploited by therapeutic bispecific antibodies. So far, the effects of CD16A-mediated activation on NK cell effector functions beyond classical antibody-dependent cytotoxicity have remained poorly elucidated. Here, we investigated NK cell responses after exposure to therapeutic antibodies such as the tetravalent bispecific antibody AFM13 (CD30/CD16A), designed for the treatment of Hodgkin lymphoma and other CD30+ lymphomas. Our results reveal that CD16A engagement enhanced subsequent IL2 and IL15¬-driven NK cell proliferation and expansion. This effect involved the up-regulation of CD25 (IL2Ralpha) and CD132 (gammac) on NK cells, resulting in increased sensitivity to low-dose IL2 or to IL15. CD16A engagement initially induced NK cell cytotoxicity. The lower NK cell reactivity observed one day after CD16A engagement could be recovered by re-culture in IL2 or IL15. After re-culture in IL2 or IL15, these CD16A-experienced NK cells exerted more vigorous IFNgamma production upon re-stimulation with tumor cells or cytokines. Importantly, after re-culture, CD16A-experienced NK cells also exerted increased cytotoxicity towards different tumor targets, mainly through the activating NK cell receptor NKG2D. Our findings uncover a role for CD16A engagement in priming NK cell responses to re-stimulation by cytokines and tumor cells, indicative of a memory-like functionality. Our study suggests that combination of AFM13 with IL2 or IL15 may boost NK cell anti-tumor activity in patients by expanding tumor-reactive NK cells and enhancing NK cell reactivity, even upon repeated tumor encounters.
This research output has an Altmetric Attention Score of 16. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 April 2026.
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Altmetric has tracked 32,178,296 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,828 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.7. This one has done well, scoring higher than 81% of its peers.
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