XMT-2056, a HER2-Directed STING Agonist Antibody-Drug Conjugate, Induces Innate Antitumor Immune Responses by Acting on Cancer Cells and Tumor-Resident Immune Cells.

ABSTRACT:

Purpose

Targeted tumor delivery may be required to potentiate the clinical benefit of innate immune modulators. The objective of the study was to apply an antibody-drug conjugate (ADC) approach to STING agonism and develop a clinical candidate.

Experimental design

XMT-2056, a HER2-directed STING agonist ADC, was designed, synthesized, and tested in pharmacology and toxicology studies. The ADC was compared with a clinical benchmark intravenously administered a STING agonist.

Results

XMT-2056 achieved tumor-targeted delivery of the STING agonist upon systemic administration in mice and induced innate antitumor immune responses; single dose administration of XMT-2056 induced tumor regression in a variety of tumor models with high and low HER2 expressions. Notably, XMT-20

SUBMITTER: Bukhalid RA 

PROVIDER: S-EPMC12010966 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature