STING activation improves T-cell-engaging immunotherapy for acute myeloid leukemia.

ABSTRACT:

Abstract

T-cell-recruiting bispecific antibodies (BsAbs) are in clinical development for relapsed/refractory acute myeloid leukemia (AML). Despite promising results, early clinical trials have failed to demonstrate durable responses. We investigated whether activation of the innate immune system through stimulator of interferon (IFN) genes (STING) can enhance target cell killing by a BsAb targeting CD33 (CD33 bispecific T-cell engager molecule; AMG 330). Indeed, we show that cytotoxicity against AML mediated by AMG 330 can be greatly enhanced when combined with the STING agonist 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) or diamidobenzimidazole (diABZI). We used in vitro cytotoxicity assays, immunoblotting, transcriptomic analyses, and extensive CRISPR-Cas

SUBMITTER: Linder A 

PROVIDER: S-EPMC12105722 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature