Identification of a Novel Linker Enabling the Bioconjugation of a Cyclic Dinucleotide for the STING Antibody-Drug Conjugate TAK-500.

ABSTRACT: STING activates the innate immune system by inducing type-1 interferon (IFN) production and has been pursued as a therapeutic option in immuno-oncology. The targeted delivery of STING agonists to CCR2+ immune cells could enhance the therapeutic window of the agonists by selectively activating the STING pathway within targeted immune cells. The chemistry strategy was established to enable the targeted delivery of the cyclic dinucleotide STING agonist dazostinag to CCR2+ cells through an antibody-drug conjugate (ADC) approach. A self-immolative spacer between the adenine of dazostinag and the Cathepsin-B cleavable Val-Ala dipeptide linker rendered a linker payload that exhibits strong plasma stability while allowing the rapid payload release upon internalization into lysosomes. The stochasti

SUBMITTER: Lee HM 

PROVIDER: S-EPMC12635970 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature