Gene-modified NK cells expressing CD64 and preloaded with HIV-specific BNAbs target autologous HIV-1-infected CD4+ T cells by ADCC.

ABSTRACT: Natural killer (NK) cells can efficiently mediate antibody-dependent cellular cytotoxicity (ADCC) of antibody coated target cells via the low-affinity Fc-receptor, CD16, but cannot retain antibodies over time. To increase antibody retention and facilitate targeted ADCC, we genetically modified human NK cells with the high-affinity Fc receptor, CD64, so that we could preload them with HIV-specific broadly neutralizing antibodies (BNAbs) and enhance their capacity to target HIV-infected cells via ADCC. Purified NK cells from the peripheral blood of control donors or persons living with HIV were activated with interleukin (IL)-2/IL-15/IL-21 cytokines and transduced with a lentivirus encoding CD64. High levels of CD64 surface expression were maintained for multiple weeks on NK cells and CD64-t

SUBMITTER: Tomescu C 

PROVIDER: S-EPMC11878998 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature