Single atom engineering for radiotherapy-activated immune agonist prodrugs.

ABSTRACT: Immunotherapy has revolutionized cancer treatment by leveraging the body's immune system to combat malignancies. However, on-target, off-tumour (OTOT) toxicity poses significant challenges, often leading to the failure of clinical trials for the development of immunotherapeutic drugs. The molecular engineering of clinically relevant, tumour-selective prodrugs, activated in a targeted way, could help minimize systemic toxicity while maximizing anti-tumour efficacy. Here, we propose a Single Atom Engineering for Radiotherapy-Activated Prodrug (SAE-RAP) technique for the development of radiotherapy-activatable small-molecule immune agonist prodrugs. We show that introducing a single oxygen atom into the TLR7/8 agonist R848 significantly reduces the EC₅₀ value by over 4000-fold, hen

SUBMITTER: Ding Z 

PROVIDER: S-EPMC12218326 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature