High-throughput drug screening identifies SMAC mimetics as enhancers of NK-cell cytotoxicity in chronic myeloid leukemia.

ABSTRACT:

Abstract

Natural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK-cell function with oncological drugs could improve NK-cell-based immunotherapies. Here, we used a high-throughput drug screen consisting of >500 small-molecule compounds, to systematically evaluate the effects of oncological drugs on primary NK cells against CML cells. We identified second mitochondrially derived activator of caspases (SMAC) mimetics as potent enhancers of NK-cell cytotoxicity in both cell lines and primary patient samples. In contrast, several drug classes, including glucocorticoids and tyrosine kinase inhibitors such as dasatinib, inhibited NK-cell cytotoxicity. Single-cell RNA sequ

SUBMITTER: Nygren P 

PROVIDER: S-EPMC12000656 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature