Despite this early promise, progress in bacteria-based cancer therapies has been slow
Imagine a
world where bacteria, typically feared for causing disease, are turned into
powerful weapons against cancer. That's exactly what some scientists are
working on.
And they
are beginning to unravel the mechanisms for doing so, using genetically
engineered bacteria to target and destroy cancer cells.
Using
bacteria to fight cancer dates back to the 1860s when William B Coley, often
called the father of immunotherapy, injected bacteria called streptococci into
a young patient with inoperable bone cancer. Surprisingly, this unconventional
approach led to the tumour shrinking, marking one of the first examples of
immunotherapy.
Over the
next few decades, as head of the Bone Tumour Service at Memorial Hospital in
New York, Coley injected over 1,000 cancer patients with bacteria or bacterial
products. These products became known as Coley's toxins.
Despite
this early promise, progress in bacteria-based cancer therapies has been slow.
The development of radiation therapy and chemotherapy overshadowed Coley's
work, and his approach faced scepticism from the medical community.
However,
modern immunology has vindicated many of Coley's principles, showing that some
cancers are indeed very sensitive to an enhanced immune system, an approach we
can often capture to treat patients.
How
bacteria-based cancer therapies work
These
therapies take advantage of the unique ability of certain bacteria to
proliferate inside tumours. The low oxygen, acidic and dead tissue in the area
around the cancer – the tumour “microenvironment” (an area I am especially
interested in) – create an ideal niche for some bacteria to thrive.
Once there,
bacteria can, in theory, directly kill tumour cells or activate the body's
immune responses against the cancer. However, several difficulties have
hindered the widespread adoption of this approach.
Safety
concerns are paramount because introducing live bacteria into a patient's body
can cause harm. Researchers have had to carefully attenuate (weaken) bacterial
strains to ensure they don't damage healthy tissue. Additionally, controlling
the bacteria's behaviour within the tumour and preventing them from spreading
to other parts of the body has been difficult.
Bacteria
live inside us, known as the microbiome, and treatments, disease and, of
course, new bacteria that are introduced can interfere with this natural
environment. Another significant hurdle has been our incomplete understanding
of how bacteria interact with the complex tumour microenvironment and the
immune system.
Questions
remain about how to optimise bacterial strains for maximum anti-tumour effects
while minimising side-effects. We're also not sure of the dose – and some
approaches give one bacteria and others entire colonies and multiple bug
species together.
Recent advances
Despite
these challenges, recent advances in scientific fields, such as synthetic
biology and genetic engineering, have breathed new life into the field.
Scientists can now programme bacteria with sophisticated functions, such as
producing and delivering specific anti-cancer agents directly within tumours.
This
targeted approach could overcome some limitations of traditional cancer
treatments, including side-effects and the inability to reach deeper tumour
tissues.
Emerging
research suggests that bacteria-based therapies could be particularly promising
for certain types of cancer. Solid tumours, especially those that have a poor
blood supply and are resistant to conventional therapies, might benefit most
from this approach.
Colon
cancer, ovarian cancer and metastatic breast cancer are among the
high-mortality cancers that researchers are targeting with these innovative
therapies. One area we have the best evidence for is that “bug drugs” may help
the body fight cancer by interacting with routinely used immunotherapy drugs.
Recent
studies have shown encouraging results. For instance, researchers have
engineered strains of E coli bacteria to deliver small tumour protein fragments
to immune cells, effectively training them to recognise and attack cancer
cells.
In lab
animals, this approach has led to tumour shrinkage and, sometimes, complete
elimination.
By
exploiting these mechanisms, bacterial therapies can selectively colonise
tumours while largely sparing healthy tissues, potentially overcoming
limitations of conventional cancer treatments.
Ultimately,
we need human trials to give us the answer about whether this works, by
controlling or eradicating cancer and, of course, if there are side-effects,
its toxicity.
In one study
I worked on, we showed that part of a bacterial cell wall, when injected into
patients, could safely help control melanoma – the most deadly form of skin
cancer.
While we're
still in the early stages, the potential of bacteria-based cancer therapies is
becoming increasingly clear. As our understanding of tumour biology and
bacterial engineering improves, we may be on the cusp of a new era in cancer
treatment.
Bacterial-based
cancer therapies take advantage of several unique mechanisms to specifically target
tumour cells. As a result, these therapies could offer a powerful new tool in
our arsenal against cancer, working in synergy with existing treatments like
immunotherapy and chemotherapy.
And, as we
look to the future, bacteria-based cancer therapies represent a fascinating
convergence of historical insight and groundbreaking science.
While
challenges remain, the progress in this field offers hope for more effective,
targeted treatments that could significantly improve outcomes for cancer
patients.
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