Researchers use bacteria that colonize the skin to create a topical cancer treatment in mice.news center

As controls, other mice were treated with either no bacteria, wild-type S. epidermidis (not expressing ovalbumin peptides), or heat-killed ovalbumin-expressing S. epidermidis.

Six days later, the scientists injected mice with melanoma tumor cells that expressed ovalbumin. All three types of control mice developed skin tumors rapidly, whereas mice treated with live, genetically engineered S. epidermidis had tumors that grew much more slowly and often did not grow at all. did not.

When researchers went looking for an explanation, ovalbumin-specific CD8 T cells were found in draining lymph nodes in the skin, the spleen, and in slow-growing tumors. In other words, T cells generated by bacterial colonization have the same level of immunity as normal killer T cells.

“Honestly, I didn’t expect it to work,” Chen said. “All other types of tumor vaccine research involve radiation, chemotherapy, or surgery, but we did very little to these mice. rice field.”

15 out of 16 tumors disappeared

To test whether their method could treat established melanoma, the researchers tried to inject cancer cells up to two weeks before colonizing with genetically engineered Staphylococcus epidermidis.

Even when melanoma metastasized to the lungs, treatment with bacteria greatly reduced or eliminated tumor size and greatly improved survival of mice. This method also worked when the researchers used naturally occurring melanoma antigens rather than ovalbumin.

The benefits were even more pronounced when researchers combined the new treatment with a second type of immunotherapy designed to enhance T-cell activity called “checkpoint blockade.” Fifteen of the tumors that had been injected disappeared. Thirty days later, when the mice were re-injected with more cancer cells, the tumors still did not grow.

“This appears to be evidence of a memory immune response,” Fischbach said, “similar to what happens after vaccination.”

Researchers now believe that the host organism produces these T cells to essentially vaccinate the colonists, protecting them from the inevitable cuts and scrapes that allow the bacteria to breach the skin barrier. I believe there is.

“In these experiments, we basically tricked the host into thinking the tumor was infected with bacteria,” Fischbach said.

Scientists have also swapped melanoma antigens for prostate tumor antigens and tested the method in a mouse model of prostate cancer. This suggests that skin-colonizing bacteria can generate potent immune responses against other than skin cancer.

Translating therapy to humans

Researchers are quick to point out that cancer treatments developed in mice don’t always work in humans. But Fischbach says there is reason for hope.First, the previous study A research team led by co-author Dr. Yasmin Belcaid, chief of the Metaorganism Immunology Section at the National Institutes of Health, has shown that S. epidermidis induces the same type of CD8 T-cell response in primates as it does in mice. Second, S. epidermidis is usually cleared from the skin of mice within a few weeks, whereas most humans are permanently colonized by certain bacterial strains.

“Human skin is a natural habitat for Staphylococcus epidermidis,” Fischbach said. “In humans, bugs may colonize more efficiently, constantly renewing their supply of tumor-specific T cells.”

Other forms of cancer immunotherapy require collecting T cells from patients, manipulating them in the laboratory to produce tumor-specific antigens, and injecting them into the same individual, often resulting in severe disease. It comes with side effects.

“We found that the host vaccinates itself every day against organisms that live on the barrier surface,” Fischbach said. “If we can direct this immune interest to specific cancers or potential infections, we could have highly effective, low-cost treatments that can be easily applied to the skin.”

Funding for this study was provided by the Stanford Microbiome Therapy Initiative, Open Philanthropy, Chau Hui Xuan Foundation, HHMI Hannah H. Gray Fellowship, Swiss National Science Foundation, Human Frontier Science Program (grant LT000493/2018-L). Astellas Metabolic Disorders Research Foundation Fellowship, NIAID Intramural Research Division (Grants 1ZIA-AI001115 and 1ZIA-AI001132), HHMI-Simons Undergraduate Scholar Award, Leona M. and Harry B. Helmsley Charitable Funds, National Institutes of Health (Grant DK110174), Chan Zuckerberg Biohub, Stand Up to Cancer, MAC3 Impact Philanthropies.