New oral nanomedicine boosts effectiveness of cancer immunotherapies
Immune checkpoint blockade is a form of cancer treatment that works by releasing the natural brakes on the immune system, allowing T cells to find and destroy cancer cells. Although it has transformed cancer immunotherapy, patients usually have low response rates. In a new study published in Nature Nanotechnology, University of Michigan researchers developed an oral drug that can increase T…
A groundbreaking study in Nature Nanotechnology reveals how an oral drug can significantly enhance the effectiveness of cancer immunotherapies. Scientists from the University of Michigan have discovered that a compound produced by gut bacteria, 3,4-dihydroxybenzoic acid (DHB), can boost the immune system's ability to attack tumors.
This natural microbial metabolite, typically produced during the breakdown of dietary fiber, was identified as a potential drug candidate. DHB works by training T cells to become memory T cells, which are crucial for effective cancer immunotherapy. However, natural compounds like DHB are poorly absorbed and quickly eliminated by the body, making them challenging to use.
To overcome this issue, the researchers created a prodrug version of DHB, encapsulating it in a protective nanoemulsion shell and converting it into an inactive precursor that becomes active after reaching target tissues. In mouse models, the oral prodrug formulation, combined with immune checkpoint blockade therapy, successfully eradicated melanoma, colorectal, and breast tumors.
The treated mice also developed long-term immune memory, preventing tumor recurrence. The researchers believe their findings could also improve the efficacy of CAR T-cell therapies, which reengineer a patient's immune cells to target cancer. The team is hopeful that their methods for formulating nanomedicines will eventually be applied in treating autoimmune diseases.
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