Engineered probiotic bacteria show promise in boosting immune response against pancreatic cancer

University of Chicago researchers have engineered a probiotic bacterial strain, BifidoSumIL-2, to deliver immune-stimulating therapy directly inside pancreatic tumors. Tested in animal models, this anaerobic bacterium selectively targets low-oxygen tumor environments, activating cancer-fighting T cells and slowing tumor growth. The treatment shows enhanced efficacy when combined with chemotherapy, radiation, or immunotherapy, offering a promising strategy to overcome pancreatic cancer's immunosuppressive barriers.

BifidoSumIL-2 engineered probiotic therapy

• ▪Researchers at the University of Chicago engineered a bacterial strain of Bifidobacterium longum, named BifidoSumIL-2, to deliver an immune-stimulating therapy directly inside pancreatic tumors.
• ▪BifidoSumIL-2 is designed to release SumIL-2, an engineered version of interleukin-2, to selectively stimulate cancer-fighting T cells while limiting the activation of regulatory T cells.

Pancreatic cancer treatment challenges

• ▪Traditional interleukin-2 therapy can cause harmful side effects and may activate immune cells that suppress the antitumor response.
• ▪Pancreatic cancer is difficult to treat because pancreatic tumors often create a cold tumor microenvironment that prevents immune cells from mounting a strong attack.

Tumor-targeted bacterial delivery mechanism

• ▪Bifidobacterium longum is a slow-growing anaerobic probiotic organism with limited genetic manipulation tools compared to model bacteria like Escherichia coli.
• ▪Bifidobacterium longum is an obligate anaerobe that thrives in low-oxygen environments, allowing it to selectively accumulate and grow in pancreatic tumors while being cleared from oxygen-rich healthy tissues.

Combination therapy efficacy results

• ▪In animal models, BifidoSumIL-2 selectively accumulated in tumors, activated CD8+ T cells, and slowed pancreatic tumor growth.
• ▪Combining BifidoSumIL-2 with chemotherapy, radiation therapy, or anti-PD-L1 immunotherapy improved tumor control and survival in animal models compared to single treatments.

Clinical translation needs

• ▪BifidoSumIL-2 has not yet been tested in humans, requiring future studies to evaluate long-term safety, durability of the immune response, and oral delivery feasibility.
• ▪Researchers plan to investigate combining BifidoSumIL-2 with newer pancreatic cancer therapies, including KRAS inhibitors.