CD16 pre-ligation by defucosylated tumor-targeting mAb sensitizes human NK cells to γ_c cytokine stimulation via PI3K/mTOR axis.

ABSTRACT: Obinutuzumab is a glycoengineered tumor-targeting anti-CD20 mAb with a modified crystallizable fragment (Fc) domain designed to increase the affinity for the FcγRIIIA/CD16 receptor, which was recently approved for clinical use in CLL and follicular lymphoma. Here we extend our previous observation that, in human NK cells, the sustained CD16 ligation by obinutuzumab-opsonized targets leads to a markedly enhanced IFN-γ production upon a subsequent cytokine re-stimulation. The increased IFN-γ competence in response to IL-2 or IL-15 is attributable to post-transcriptional regulation, as it does not correlate with the upregulation of IFN-γ mRNA levels. Different from the reference molecule rituximab, we observe that the stimulation with obinutuzumab promotes the upregulation of microRNA (miR)-1

SUBMITTER: Capuano C 

PROVIDER: S-EPMC7113231 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature