Cell-selective telomere damage by thiopurine-based oligonucleotide for diffuse large B cell lymphoma immunotherapy.

ABSTRACT: Telomerase (TERT) is an enzyme involved in maintaining telomere length in diffuse large B cell lymphoma (DLBCL). Previous attempts to target TERT⁺ cancers faced challenges, including the delayed clinical responses and on-target/off-tumor toxicities. Here, we present a DLBCL-targeted oligonucleotide designed to deliver a synthetic TERT substrate, 6-thio-2'-deoxy-guanosine (6tdG), damaging telomeres and triggering apoptosis. In vitro, 6tdG-oligonucleotides (6tdGOs) were selectively cytotoxic to TERT⁺ DLBCL cells without affecting activated T cells or non-malignant TERT^- cells. Repeated intravenous administration of 6tdGO, but not 6tdG nucleoside, had significant antitumor effects against xenotransplanted human DLBCL models and syngeneic Eμ-myc/15A lymphoma in

SUBMITTER: Yu C 

PROVIDER: S-EPMC12380039 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature