UMC Utrecht and its partners have received a research grant to unravel how the intestinal microbiota can be exploited to boost cancer immunotherapy and limit therapy side-effects.
Close to €800,000 was awarded by Health~Holland to a public-private partnership between UMC Utrecht, Artizan Biosciences, Inc. (USA) and MicroViable Therapeutics (Spain).
The project will be headed by Marcel de Zoete, PhD of the Department of Medical Microbiology at UMC Utrecht.
Immune checkpoint inhibition (ICI) therapies enable the treatment of an increasing number of metastatic cancers and are designed to (re)activate potent anti-tumor T-cell responses.
The bacteria in the intestinal tract (‘microbiota’) play an important role in the success of ICI therapy, suggesting that crosstalk between the immune system and bacteria in the intestine can impact the overall anti-tumor T-cell activation status.
However, despite being well tolerated by part of the patients and ICI toxicity (immune-related adverse events or irAEs) can be severe, irreversible and even fatal. These adverse events often present in the intestinal tract as severe inflammation. Again, the composition of the microbiota is believed to be a key determinant for toxicity.
As part of the study, a large biobank of patient material from cancer patients prior to and during ICI therapy will be investigated, immune-stimulatory bacteria will be identified and isolated, and molecular mechanisms will be unraveled using various in vitro and in vivo models.
UMC Utrecht and its partners aim to provide a rationale for microbiota-targeted therapy that maximises efficacy of therapy while minimalising intestinal adverse events.
“In up to 56% of irAE cases in ICI-treated patients, symptoms present in the intestinal tract as moderate to severe intestinal inflammation, resembling what is seen in patients with inflammatory bowel disease,” said Marcel de Zoete, PhD, Associate Professor of Microbiome Research at the Department of Medical Microbiology at UMC Utrecht. “Recent data demonstrate a clear correlation between ICI-induced irAE severity and overall cancer survival. The key challenge is how to maximise ICI therapy effectiveness while minimising irAEs.”
