Oral nanomedicine improves cancer immunotherapy by harnessing gut bacterial metabolite

A team of researchers from the School of Medicine and the University of Michigan have created the world's first oral nanomedicine that significantly boosts the effectiveness of cancer immunotherapy by utilizing gut bacterial metabolites. Immunotherapy, such as anti-PD-1 drugs, has shown promise in reactivating the body's immune system to fight cancer, but its success rate varies among patients.

The researchers focused on the connection between the gut microbiome and immunity, discovering that a metabolite called 3,4-dihydroxybenzoic acid (DHB) boosts the immune system and prolongs the lifespan of cancer-fighting CD8+ T cells. However, natural DHB breaks down quickly in the body, limiting its potential as a treatment. To solve this issue, the team developed an oral nanomedicine with DHB in a stable prodrug form and encapsulated it in an oleic acid-based nanoemulsion.

This oral nanomedicine, named Prodrug 201, enhances the drug's bioavailability by 14.3 times, allowing it to stay in the bloodstream longer and reach tumor sites more effectively. In animal models with colorectal cancer, melanoma, and breast cancer, the oral nanomedicine successfully targeted refreshed, stem-like T cells to the tumor sites, resulting in significant tumor reduction.

When combined with immune checkpoint blockade therapy, it led to complete tumor eradication and long-term immune memory, preventing cancer recurrence. This groundbreaking study, published in Nature Nanotechnology, demonstrates the potential of harnessing gut bacterial metabolites in developing a convenient oral medication for microbiome-based cancer immunotherapies.