STING Agonist VB-85247 Induces Durable Antitumor Immune Responses by Intravesical Administration in a...

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Bacillus Calmette-Guérin (BCG) is the standard treatment for non-muscle-invasive bladder cancer (NMIBC), but high recurrence rates necessitate new therapies.
• Patients unresponsive to BCG require alternative treatment options, highlighting a significant unmet medical need.

Purpose of the Study:

• To develop and evaluate a novel Stimulator of Interferon Genes (STING) agonist, VB-85247, for intravesical delivery in NMIBC.
• To assess the efficacy and immunomodulatory effects of VB-85247 in preclinical NMIBC models.

Main Methods:

• Development of STING agonist VB-85247 for intravesical administration.
• Evaluation of VB-85247 efficacy in an orthotopic NMIBC model compared to BCG.
• Assessment of immune responses, including cytokine profiles and dendritic cell activation.
• Combination therapy studies with anti-PD-1 antibodies.

Main Results:

• VB-85247 induced complete tumor regression in an NMIBC model, outperforming BCG.
• The treatment was well-tolerated and generated immunologic memory, protecting against tumor rechallenge.
• VB-85247 upregulated key inflammatory cytokines (IFNα/β, TNFα, IL6, CXCL10) and promoted dendritic cell maturation.
• Combination therapy with anti-PD-1 antibody showed additive therapeutic benefits.

Conclusions:

• Intravesical STING agonist VB-85247 demonstrates significant potential for treating BCG-unresponsive NMIBC.
• VB-85247 induces robust anti-tumor immunity and enhances efficacy when combined with immune checkpoint inhibitors.
• These preclinical findings support the clinical development of VB-85247 for NMIBC treatment.