The concept of using bacteria to treat cancer dates back to the early 1800s, long before the advent of modern cancer treatments like chemotherapy or radiotherapy. Historical evidence suggests that rudimentary and crude forms of immunotherapy were practiced as early as Ancient Egypt. However, these early treatments of cancer using immunotherapy were risky and unreliable due to the lack of antibiotics and the potential for severe side effects.
More recently, with advancements in genetic modification, researchers have revisited bacterial therapies, aiming to genetically modify the bacteria to preserve their anti-cancer properties while ensuring patient safety. One of the most promising bacteria in this field is Salmonella, which has been engineered to target cancer cells without harming patients.
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The Role of Salmonella in Cancer Treatment
Salmonella, a genus of gram-negative bacteria, is well-known for causing food poisoning. However, its ability to take over tumours and inhibit their growth has made it a candidate for cancer therapy. Specifically, Salmonella Typhimurium has been engineered to express anti-cancer agents, making it a promising tool in the fight against cancer. Recent studies have shown that modified Salmonella can survive longer in tumours than in normal tissues, allowing it to selectively target cancer cells.
The modern approach involves genetically modifying bacteria like Salmonella to retain their cancer-fighting capabilities while eliminating harmful effects. Researchers indicate that Salmonella attacks the bowels and causes food poisoning, making it a perfect candidate for the treatment of bowel tumours. This research is imperative to turning once-dangerous pathogens like Salmonella into a standardised treatment option for cancer patients.
Recent research has focused on understanding why bacterial therapies, despite their potential, have not been as effective as hoped. A key issue is their impact on the immune system, particularly T-cells, which are important for fighting cancer. T-cells, cancer cells and bacteria have a particular nutrient vital to their composition and operation, an amino acid known as asparagine. T-cells require asparagine to function optimally and Salmonella’s depletion of these nutrients has been identified as a major obstacle.
Breakthrough in Salmonella-Based Therapies
A major breakthrough came from a joint study by researchers at the University of Birmingham and the University of Glasgow. This research, published in EMBO Molecular Medicine, explored how Salmonella interacts with T-cells in mouse models of bowel cancer. The study found that Salmonella depletes asparagine, an amino acid essential for both cancer cell growth and T-cell activation. While this depletion slows tumour growth, it also suppresses T-cell activity, preventing them from effectively targeting cancer cells.
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Mechanism of Action
The mechanism involves Salmonella competing with cancer cells for nutrients, effectively starving tumours of essential resources fundamental to its functionality. However, this competition also affects T-cells, which need these nutrients to function. By identifying asparagine as the key nutrient, researchers have pinpointed a genetic target for modification. This could enable the development of Salmonella strains that do not deplete asparagine, allowing T-cells to work together with the bacterial therapy to combat cancer more effectively.
The next steps involve further engineering Salmonella to selectively target asparagine in cancer cells without affecting T-cells. This could involve targeting genes like c-Myc, which drives cancer growth but is difficult to target with conventional drugs. This particular gene could be the key in fully unlocking the potential benefits of this therapy. The goal is to create a two-tiered approach where Salmonella weakens tumours while T-cells attack them, offering a more effective cancer treatment.
Clinical Trials and Outcomes
While the current research focuses on bowel cancer, other studies have shown promising results with Salmonella in different cancer types. For instance, a phase II clinical trial involving patients with metastatic pancreatic cancer used modified Salmonella expressing the immune-stimulating protein IL-2. Patients treated with this regimen showed a median overall survival of 24 months, compared to 13 months for those receiving standard chemotherapy alone.
Challenges and Opportunities
Despite these advances, challenges remain. Bacterial therapies are not yet mainstream due to historical safety concerns and the complexity of immune system interactions. However, recent progress in genetic modification has made it possible to engineer bacteria that are both safe and effective. The key is to balance the cancer-fighting capabilities of bacteria like Salmonella with their impact on the immune system, ensuring that they enhance rather than hinder the body’s natural defenses.
The future of bacterial cancer therapies looks promising. As researchers continue to refine their understanding of how bacteria interact with the immune system, they are developing more sophisticated tools to fight cancer. Researchers’ next step is to investigate how well these bolstered T-cells work with Salmonella against bowel cancers. By finding a way to use Salmonella to specifically deplete asparagine from cancer cells without inhibiting T-cells’ functionality, the potential to improve cancer treatment could significantly impact survival rates and give various treatment options for patients with various types of cancer.
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