STING Agonist 8803 for Blood-Brain Barrier Opening in Glioblastoma Treatment

SHORT DESCRIPTION

Chemical compound that opens the blood-brain barrier to enhance delivery of therapeutics for treating glioblastoma.

• Amy Heimberger*
  • Northwestern University Feinberg School of Medicine, Department of Neurological Surgery

NU Tech ID: NU 2025-212

IP STATUS

US Patent Pending

DEVELOPMENT STAGE

TRL-3 Experimental Proof-of-Concept: Active R&D is initiated with robust preclinical studies in murine glioma models.

BACKGROUND

The blood-brain barrier (BBB) is a highly selective interface that regulates the exchange of substances between the bloodstream and the brain, preserving the stable conditions required for normal brain activity. While this barrier plays a critical role in protecting neural tissue from harmful agents, it also greatly limits the delivery of many therapeutic agents to the brain. As a result, effective treatment of neurological disorders such as brain tumors, Alzheimer’s disease, and Parkinson’s disease is challenging. Current treatments for brain tumors face challenges such as high cost, invasiveness, and poor permeability. Clinicians and researchers need improved methods that safely and effectively open the BBB to allow better treatment of neurological diseases.

ABSTRACT

Northwestern researches found that STING Agonist 8803 is a chemical compound that opens the BBB to improve drug delivery for glioma treatment. The small molecule 8803 increases BBB permeability through targeted activation of endothelial cells lining the brain microvasculature. By precisely modulating endothelial tight junctions, 8803 enables the safe and efficient delivery of drugs, biologics, and cell-based gene therapies to the brain. Preclinical studies in mouse models show that combining 8803 with radiation therapy increases survival outcomes. It also enables non-invasive monitoring of BBB opening using PET imaging. This approach is broadly applicable across neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and brain tumors. Importantly, 8803 supports combination strategies that enhance the brain delivery of existing CNS therapeutics with poor intrinsic BBB penetration, reducing development risk while accelerating timelines and improving therapeutic efficacy.

APPLICATIONS

• Glioblastoma treatment: Enhances delivery of therapeutics across the BBB.
• Combination therapy with radiation: Improves immune infiltration and survival outcomes.
• Non-invasive BBB modulation: Supports improved imaging and therapeutic monitoring.

ADVANTAGES

• Rapid BBB opening: Achieves diffuse barrier modulation within hours.
• Enhanced immune response: Activates anti-tumor immunity to support therapeutic outcomes.
• Synergistic with radiation: Provides added value when combined with standard radiation treatments.
• Non-invasive monitoring: Uses [18F]-FLT PET imaging for real-time assessment of BBB status.

PUBLICATIONS

• Najem H et al., STING agonist 8803 reprograms the immune microenvironment and increases survival in preclinical models of glioblastoma. J Clin Invest. Jun 17,  2024.

• Youngblood, MW et al., STING activation induces cytotoxic and immune responses in meningiomas via inflammatory cell death pathways. Nat Commun. Feb 12,  2026.

• Tripathi, S et al. STING-Induced Blood-Brain Barrier Opening Combined with Radiotherapy Potentiates Antitumor Response in a High-Grade Glioma Model. J Clin Invest. Feb 16, 2026

• Rohman, M. Targeting STING Pathway Triggers Cytotoxic and Immune Responses Against Meningioma. Feinberg School of Medicine News Center. Feb 19, 2026.