Can your microbiome fight cancer? WIRED Health speaker and Evelo Biosciences CEO Simba Gill is trialing ways to harness microbes against an array of cancers
In 2015, Thomas Gajewski was researching new treatments for cancer when he noticed something unusual in his lab mice. Gajewski is a professor of medicine and pathology at the University of Chicago, and his lab gets its mice from two different suppliers, Jackson Laboratory (JAX) and Taconic Biosciences (TAC). When the scientists implanted small tumours under the skin of the JAX mice, the animals’ immune systems fought the cancer rigorously. The TAC mice, in contrast, would show only a weak immune response. Mix the two sets together in a cage for a few weeks, and the difference was abolished. The TAC mice were able to fight the cancer with the same vigour as the JAX animals.
Gajewski realised that the difference could be explained by discrepancies between the animals’ microbiomes, the teeming mass of bacteria and other microbes that live in the gut of all living creatures. Something in the gut of the JAX mice dramatically improved its ability to deal with cancer, and the effect was transferred to the TAC mice after the two sets swapped bacteria (endearingly, mice eat each other’s poop). The close connection between the gut microbiome and the immune system has only recently been made. Gajewski’s finding pointed to a way to exploit the connection – to improve the body’s resilience by manipulating the gut.
This is the sort of finding that greatly interests Simba Gill, the chief executive of Evelo, a biotech company based in Cambridge, Massachusetts. Evelo was established three years ago in order to develop a suite of new medicines based on the understanding that the gut-body network plays a critical role in our biology and immunology. The company has so far raised $100 million; investors include Flagship Pioneering, Google Ventures and Mayo Clinic.
Evelo’s remit goes beyond cancer. The company is currently investigating treatments for multiple sclerosis, rheumatoid arthritis, asthma, inflammatory bowel disease and diabetes, to name a few. This year, Evelo will begin clinical trials of some of its medicines, called monoclonal microbials – “monoclonal” because each medicine harnesses a single microbe strain. It was recently issued a patent for a cancer treatment based on Gajewski’s work. “The core of what we’re doing now is in recognition of the fact that the gut is networked to the rest of the body and drives many of the central aspects of how we fight disease,” Gill says.
Gill has worked in biotechnology for three decades. After his PhD at King’s College, London, he worked for Celltech in the early days of antibody engineering. Later, he worked at a company that uses stem cells to treat diseases, and spent a decade collaborating with biotech entrepreneur Alejandro Zaffaroni. “I’ve focused my whole career on big, bold platform biotech ideas,” Gill says. “What I mean by platform is a new modality of medicine which has very broad applicability, that can allow for many products to treat diseases in ways which have not otherwise been possible.” In 2015, he joined Flagship Pioneering, a builder and funder of platform biotech start-ups.
For centuries, medical science ignored the trillions of microorganisms that share our bodies – it was the dangerous invaders that needed attention. In the past decade, we have come to appreciate better the role that these microbes play in an array of bodily functions, from digestion and immunity to organ health and even things like mood, sleep and stress. The gut contains 99% of the body’s microbial mass, representing thousands of species. “Humans evolved together with microbes,” says Gill. “What we hypothesised was, because of that reason, it was very likely that there were specific, individual microbial strains which have evolved to act through the gut with the immune system to modulate our systemic biology.” If Evelo could only find these individual strains, they might use them to develop a new class of medicine.
Monoclonal microbials work by commandeering one of the body’s routine immunological processes. The idea is to load a capsule with a single strain – perhaps tens of billions of microorganisms. After the capsule is swallowed, it makes its way to a part of the small intestine that is lined with gut-associated lymphoid tissue. Through the tissue interface, dendritic cells sample the gut and alert the lymphatic system to changes. Depending on which microbe is detected, a specific immune response is hatched. In the case of cancer, Gajewski’s team found that when Bifidobacterium (Bifs) was introduced to the digestive track of a mouse, it boosted the ability of animal’s immune system to attack tumour cells.
Gill admits that a lot of work still needs to be done. “It’s very difficult to find the strains which have the [desired] type of activity,” he says. And while models (mouse and computer) have been encouraging, trials in humans need to be carried out. It is in people that most promising new medicine falls down.
But if trials are successful, Gill believes that microbes could be harnessed against an array of cancers including colon, lung, melanoma, renal, bladder and head and neck cancer, either alone or in combination with existing immunotherapies. In the lab, when specific strains of Bifs were combined with a type of immunotherapy drug called a checkpoint inhibitor, the tumour growth in mice was nearly abolished.
More broadly, Gill sees a gap in the market for effective early-stage treatments for disease. “Modern medicine is still very limited,” he says, pointing out that many conditions are not treated until the late stages because the treatment might be expensive, have side effects or require professional administration. Monoclonal microbials, in contrast, could be swallowed at home. He thinks that they could be used as a preventative medicine, one that ensures that the gut-body network stays in healthy, homeostatic balance. Such a thing is not a new concept, he points out. It was just that, for a long time, he found it hard to imagine how it could be done.