STING agonist combined with Vps34 inhibitor results in markedly reduced tumour size

April 2024 Science Willem van Altena

Researchers in Luxembourg have uncovered a new approach for shrinking tumours. Their findings, recently published in Molecular Oncology Journal, outlines a potent immunotherapy combination. This combination involves pairing a STING agonist, which enhances the immune system, with a compound that targets autophagy, a mechanism implicated in cancer immune evasion. This dual therapeutic approach markedly reduced tumour size and improved survival rates in preclinical studies, offering new hope of shifting the paradigm in cancer treatment.

Groundbreaking research

A collaborative team effort led by the Tumor Immunotherapy and Microenvironment (TIME) group at the Luxembourg Institute of Health, along with Sprint Bioscience and Karolinska Institutet (Sweden) has published groundbreaking research article in the Molecular Oncology Journal, outlining a promising new strategy for cancer treatment. This strategy focuses on unlocking the full potential of STING agonists, a new class of drugs designed to boost the body’s immune system to fight cancer.

Cancer cells can employ various strategies to evade the body’s natural defences, rendering existing immunotherapies ineffective. Previous research work by the TIME group and Sprint Bioscience showed how inhibiting a specific protein (Vps34) involved in this immune evasion could enhance the effectiveness of existing cancer immunotherapy based on checkpoint blockades. Building upon this success, the latest study explores the exciting synergy between Vps34 inhibitors and STING agonists.

Robust response

STING agonists work by stimulating a pivotal protein known as STING, which acts as a central coordinator of the immune system. Upon activation, STING triggers a robust response against cancer cells, mobilizing and empowering diverse immune cells, including T cells, natural killer cells, and dendritic cells.

The new research demonstrates that combining a Vps34 inhibitor with a STING agonist results in a potent double atack on tumours. This combination significantly shrinks tumours and improves survival rates in preclinical studies, offering a potential paradigm shift in cancer treatment.

“This research offers a new hope for overcoming the several disappointments encountered in past clinical trials with STING agonists,” explains Dr Bassam Janji, Head of the TIME group. “By enhancing the STING pathway and circumventing cancer’s immune evasion strategies, we have the potential to develop durable and powerful new immunotherapies.” This exciting research paves the way for further development, aiming to bring the promise of STING agonists to cancer patients.

Reference

Yu Y, Bogdan M, Noman MZ, Janji B, et al. Combining VPS34 inhibitors with STING agonists enhances type I interferon signaling and anti-tumor efficacy. Mol Oncol. 2024 Mar 20. doi: 10.1002/1878-0261.13619. Epub ahead of print. PMID: 38506049.