Chemical anchoring of immunotherapeutic drugs within senescent tumor cells overcomes senescence-driven immunotherapy resistance - PubMed
5 hours ago
- #Immunotherapy Resistance
- #Drug Anchoring
- #Senescence
- Researchers developed a chemical anchoring approach to overcome senescence-driven immunotherapy resistance in cancer treatment.
- A senescent-tumor-targeted immunotherapeutic drug, DN-Ghcy, was created, combining a SA-β-gal-activatable bio-orthogonal receptor and an immunostimulatory prodrug.
- DN-Ghcy selectively immobilizes in senescent tumor cells, bypassing drug efflux and enabling drug retention via SA-β-gal-catalyzed reactions.
- Under near-infrared irradiation, DN-Ghcy mediates PD-L1 degradation, IDO inhibitor release, and lysosomal disruption, reversing immunotherapy resistance in female mice with senescent tumors.