University of Chicago scientists turn probiotic bacteria into pancreatic cancer drug factories
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University of Chicago researchers have engineered a strain of probiotic bacteria that carries an immune-stimulating treatment directly into pancreatic tumors and slowed tumor growth in animal models. The therapy, BifidoSumIL-2, selectively activated cancer-fighting T cells and grew more effective when combined with chemotherapy, radiotherapy, or immunotherapy, according to a study published in Science Advances.
Key Facts
- University of Chicago researchers created BifidoSumIL-2, an engineered strain of the probiotic bacterium Bifidobacterium longum, to release a modified version of the immune signaling molecule IL-2 inside tumors.
- In animal models, BifidoSumIL-2 slowed pancreatic tumor growth by selectively activating T cells that fight cancer.
- The therapy's effects became stronger when researchers combined it with chemotherapy, radiotherapy, or immunotherapy.
- Bifidobacterium longum grows in anaerobic, low-oxygen environments that are common inside many solid tumors, including pancreatic tumors, while healthy tissues generally contain more oxygen.
- Conventional IL-2 treatment can produce serious side effects and stimulate immune cells that weaken the antitumor response, prompting the use of engineered SumIL-2.
Probiotic Engineering
BifidoSumIL-2 was created to release a modified version of interleukin-2, a potent immune signaling molecule that activates T cells involved in attacking cancer, once it reaches a tumor. Conventional IL-2 treatment can produce serious side effects and can also stimulate immune cells that weaken the antitumor response. Researchers used SumIL-2, a modified form of IL-2 engineered to more precisely activate cancer-fighting T cells while reducing stimulation of regulatory T cells. They placed SumIL-2 inside Bifidobacterium longum so the therapeutic molecule could be concentrated within tumors instead of throughout the body. Developing the treatment required specialists from four disciplines: microbiology, synthetic biology, oncology, and immunology.
Tumor Delivery Mechanism
Bifidobacterium grows in anaerobic environments, meaning places with very little oxygen. Low oxygen levels are common inside many solid tumors, including pancreatic tumors, while healthy tissues generally contain more oxygen and are therefore less suitable for the bacteria. The bacterium's preference for low-oxygen tumor regions offered researchers one unusual advantage as a delivery system. Ralph Weichselbaum, chair of radiation and cellular oncology at the University of Chicago, called pancreatic cancer 'a big unmet medical need' and a mountain to climb. Mark Mimee, assistant professor of microbiology at the University of Chicago, described the work as a highly interdisciplinary effort that brought together specialists in bacteria, tumors, and the immune system.
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University of Chicago scientists turn probiotic bacteria into pancreatic cancer drug factories
