Next-Generation HER-2 Tumor-Targeted Delivery of the STING Agonist Immune-Stimulating Antibody Conjugate (ISAC) Improves Anticancer Efficacy and Induces Immunological Memory.

ABSTRACT: Recently, rapidly evolving STING-based immunotherapies have offered novel therapeutic options for various cancer types. However, systemic administration of STING agonists raises safety concerns, and intratumoral injection is constrained by tumor accessibility. Herein we developed an immune-stimulating antibody conjugate (ISAC) that links STING agonists to antibodies that target HER2-positive tumor cells via a cleavable linker. In vivo studies demonstrated that the STING agonist ISAC is well tolerated and exhibits potent antitumor activity in syngeneic mouse tumor models. Investigations in STING-knockout HER2-positive tumor cells and STING-knockout mouse models revealed that the STING pathway primarily mediates antitumor effects upon the activation of immune and tumor cells and that the act

SUBMITTER: Wu G 

PROVIDER: S-EPMC12214944 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature