Bacteria are quickly emerging as a new class of “living medicines” used to eliminate cancer cells.
We are still far from finding a “cure” for cancer. But one day we may have programmable bacteriacapable of finding their way to tumors on their own, delivering treatment only where necessary and then disappearing without a trace.
Current treatments against different types of cancer are not perfect; many tumors are difficult to treatand in some cases there are currently no effective treatments.
Sometimes, treatments cannot penetrate to the sites of neoplasia. In other situations, tumors are able to “fight back”suppressing certain parts of the immune system and thus reducing the effect of treatments. Or, tumors develop resistance to treatments.
A use of bacteria can help overcome these obstacles, they explain Josephine Wright e Susan Woodsresearchers from the South Australian Health & Medical Research Institute, in Australia, in an article in .
More than a century ago, some surgeons noticed that people with cancer who developed bacterial infections came in unexpectedly in remission. In other words, the signs or symptoms of cancer decreased or disappeared.
Now, we begin to understand what can explain this phenomenon. In general terms, Bacteria can activate the body’s immune system to attack cancer cells.
In fact, this approach already used in clinical settings. Around the world, the treatment of choice for certain cases of bladder cancer involves bacteria.
When doctors introduce a toned-down version of Mycobacterium bovis directly into the bladder, through a catheter, body’s immune response destroys cancer.
Why bacteria?
Certain bacteria have an unusual ability: they can, naturally, localize and proliferate within solid tumors – those that grow in organs and tissues – leaving healthy tissue virtually untouched.
Os solid tumors are the ideal habitat for these bacteria, as they contain many nutrients from dead cells, they have low oxygen levels (an environment preferred by these bacteria) and, normally, they have a reduced immune function, unable to defend themselves against the bacteria.
All this suggests a possible future for these bacteria as carriers of targeted therapies against tumors.
Over the last 30 years, there have been published more than 500 scientific articlescarried out 70 clinical trials and founded 24 startups focused on bacterial therapy against cancer, with a strong increase in this interest in the last five years, note Wright and Woods.
Currently, most bacterial therapies in clinical trials target solid tumors, including pancreatic, lung, head and neck cancer – types often resistant to conventional treatments.
Currently, cancer vaccines work by presenting the immune system with unique molecular “fingerprints” of cancerknown as tumor antigensso that it can identify and eliminate the tumor cells that exhibit them.
Bacteria can serve as carriers of these anticancer vaccines. Through genetic engineering, it is possible to remove DNA from bacteria that could cause disease and replace it with DNA that encodes tumor antigens that stimulate the immune system.
A Listeria monocytogenes is the protagonist of more than 30 clinical trials of cancer vaccines. Unfortunately, most of these trials have not demonstrated that these treatments are superior to current treatments.
O main challenge is to teach the immune system to recognize the antigens characteristic of cancer in a strong enough to memorize themwithout provoking an excessive and dangerous immune response.
Bacteria can enhance existing therapies
About half of current clinical trials using bacteria in cancer therapies arecombine them with immunotherapies or chemotherapyas part of personalized treatment plans to strengthen the body’s attack on cancer.
Several approaches have already completed phase 2 clinical trials. Among them is the use of immunotherapy combined with Listeria modified to activate the immune system in case of recurrent cervical cancer.
Another trial used Salmonella modified in people with advanced pancreatic cancer, in conjunction with chemotherapy, to increase survival, explain the two researchers. Arming bacteria with drugs means they can destroy the tumor from withincreating “microorganisms as medicines”.
To do this, you need a precise genetic control the behavior of bacteria. Researchers can now reprogram bacteria to detect, process and respond to molecular signals around the tumor.
It is also possible Program bacteria to self-destruct after releasing the medicine, which secrete molecules that reinforce the immune systemor that activate other therapies on command.
Furthermore, Wright and Woods note, “multipurpose” strains are being developed that combine several treatment strategies simultaneously.
Probiotic species used for many years in humans are also candidates, including Escherichia coli Nissle, Lactobacillus e Bifidobacterium. These can be modified to produce molecules that kill cancer or to alter the environment around the tumor.
After all, how close are we?
Although early human trials have shown that this approach is generally safe, find the correct dose It remains a delicate balance.
Bacteria are also living beings that can evolve in unpredictable ways, and their use in humans requires strict security controls. Even strains engineered to be safe can cause infections or trigger excessive inflammation.
Therefore, scientists are developing “biocontainment” strategies” – safety mechanisms that prevent the spread of bacteria beyond tumors or that lead to self-destruction after treatment.
If we can overcome these challenges, these “live medicines” will still have to successfully complete clinical trials and obtain regulatory approval before they can be routinely used in a clinical setting.
If this happens, we could see a profound change in the way we treat cancer: from static medicines to biological systems adaptive, conclude Wright and Woods.
