A recent study has shown how a skin-colonising bacteria could be used to treat cancer. The work, published in Science, describes how a genetically engineered Staphylococcus bacteria could be applied as part of a topical treatment to combat melanoma, after showing promising results in mice.
Makes your skin crawl
The skin is covered in millions of microbes, which typically exist in harmony with the host and do not trigger a significant immune response. Nonetheless, there are always exceptions to the rule. For example, the bacterial species Staphylococcus epidermidis is known to elicit a strong adaptive immune response in the form of CD8 T cell production in the host. Despite this, there is no accompanying inflammation, and the role of the immune cells in wound healing is an atypical function for a CD8 T cell to exhibit.
Whilst studying the immune response to S. epidermidis in mice, the team from Stanford Medicine chose to engineer a tumour-specific antigen into the bacteria to determine if the immune cells produced in response to colonisation could be re-engineered to act like a regular T cell.
The researchers engineered ovalbumin into both the bacteria and melanoma cells. After applying the bacteria topically and allowing it to colonise the mice’s skin, the animals were injected with the cancer cells. Following this, researchers confirmed that the mice were expressing ovalbumin-specific T cells. These cells sought out and destroyed the ovalbumin-expressing tumour cells, preventing disease progression.
These results were further validated by an experiment in which the melanoma cells were injected prior to S. epidermidis exposure and left to metastasise. Even in these severe cases, the bacterial treatment appeared to halt disease progression. The results were mirrored when the ovalbumin antigen was replaced with a melanoma-specific trigger.
The ease with which this non-invasive, topical treatment can be applied makes it an exciting prospect. In combination with other therapies, it was even more effective, and showed signs of immune memory that prevented the return of the tumours. Discussing the potential clinical applications in humans, the authors stressed that, whilst efficacy in mice does not always translate to efficacy in humans, S. epidermidis is a natural coloniser of human skin and induces similar immune responses.
Senior author Michael Fischbach stated: “In humans, the bug will colonize more efficiently, potentially leading to a constantly renewing supply of tumour-specific T cells.” He added: “We’ve discovered that the host is vaccinating itself, day in and day out, against organisms that live at barrier surfaces. If we can direct even a bit of this immune attention toward specific cancers — or potentially infectious diseases — we will have a very effective, low-cost therapy that can simply be applied to the skin.”