Australian Scientists Employ Bacteria as 'Living Medicines' to Combat Cancer
Despite significant progress, a definitive 'cure' for cancer remains elusive. However, the future may hold a groundbreaking approach: self-navigating bacteria that can detect tumors, administer targeted treatments, and then disappear without a trace. This article delves into the current state of this innovative scientific endeavor.
Current cancer treatments face several limitations. Tumors often prove resistant, and treatments may struggle to penetrate them. Additionally, tumors can suppress the immune system, reducing the effectiveness of treatments, or even develop resistance to them. Employing bacteria as a therapeutic tool could potentially overcome these challenges.
A century ago, surgeons observed that individuals with cancer who developed bacterial infections unexpectedly entered remission, marked by a decrease or disappearance of cancer symptoms. Scientists are now unraveling the underlying mechanisms. Bacteria can stimulate the body's immune system to target cancer cells. This method is already utilized in clinical settings, particularly for bladder cancer. By introducing a weakened version of Mycobacterium bovis into the bladder via a catheter, the immune system is triggered to destroy the cancer.
The choice of bacteria is not arbitrary. Certain bacteria possess a unique ability to locate and thrive within solid tumors, which form in organs and tissues, while leaving healthy tissue largely unaffected. Solid tumors provide an ideal environment for these bacteria due to their nutrient-rich nature, low oxygen levels, and compromised immune function, making them susceptible to bacterial colonization.
This has sparked interest in utilizing these bacteria as delivery vehicles for targeted anti-tumor therapies. Over the past three decades, over 500 research papers, 70 clinical trials, and 24 startup companies have focused on bacterial cancer therapy, with rapid growth observed in the past five years. Current clinical trials primarily target solid tumors, including pancreatic, lung, and head and neck cancers, which often resist conventional treatments.
Bacteria can also be employed to deliver cancer vaccines. Cancer vaccines work by presenting the immune system with unique molecular markers of cancer, known as tumor antigens, enabling the immune system to identify and eliminate tumor cells displaying these antigens. Bacteria can act as couriers for these vaccines, with genetic engineering used to remove harmful bacterial DNA and replace it with DNA encoding immune-stimulating tumor antigens.
Listeria monocytogenes is a key player in over 30 cancer vaccine clinical trials. However, most of these trials have not demonstrated superior efficacy compared to existing treatments. The challenge lies in teaching the immune system to recognize cancer antigens strongly enough to remember them without causing excessive immune system activation.
Bacteria can also enhance existing cancer therapies by combining them with immunotherapies or chemotherapy as part of personalized treatment plans. Several approaches have completed phase 2 clinical trials, such as using immunotherapy alongside modified Listeria to activate the immune system for recurrent cervical cancer. Another trial utilized modified Salmonella in conjunction with chemotherapy to improve survival rates in individuals with advanced pancreatic cancer.
Furthermore, bacteria can be engineered to release drugs directly into tumors, creating 'bugs as drugs'. Researchers have already demonstrated the ability to reprogram bacteria to sense, compute, and respond to molecular signals around tumors. They can also engineer bacteria to self-destruct after drug delivery, secrete immune-boosting molecules, or activate other therapies on command.
Scientists are developing 'multi-function' bacterial strains that combine multiple treatment strategies simultaneously. Probiotic species like Escherichia coli Nissle, Lactobacillus, and Bifidobacterium, which have been used in humans for years, are also being engineered to produce cancer-killing molecules or alter the tumor environment.
While early human trials have shown the approach's safety, finding the optimal dosage remains a critical challenge. Bacteria are living organisms that can evolve unpredictably, and their use in humans requires stringent safety measures. Even strains modified for safety can potentially cause infections or trigger excessive inflammation.
To address these concerns, scientists are developing 'biocontainment' strategies, which include engineered safeguards to prevent bacterial spread beyond tumors or trigger self-destruction after treatment. If these issues are overcome, 'living medicines' would need to complete clinical trials and receive regulatory approval before becoming a common clinical practice.
This potential shift from static drugs to adaptive biological systems could revolutionize cancer treatment, marking a significant advancement in the field.
