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Alliance Exploring Microbiome on Cancer Immunotherapy

Gut bacteria illustration

Bacteroides thetaiotaomicron, in white, a type of bacteria living on mammalian cells in the gut (MIT Media Lab/NIH)

14 November 2017. A biotechnology company and two research institutes are collaborating on a study of a proposed cancer treatment that targets the microbiome, communities of bacteria in the human body. The project will assess a treatment developed by Seres Therapeutics Inc. in Cambridge, Massachusetts at MD Anderson Cancer Center in Houston, sponsored by the Parker Institute for Cancer Immunotherapy in San Francisco.

Seres Therapeutics discovers and develops therapies related to disruptions in the microbiome, the complex aggregate community of diverse intestinal microbes associated with a wide range of health conditions. These disruptions to the microbiome known as dysbiosis  — resulting from pathogens, antibiotics, diet, or inflammation — are increasingly connected or contribute to many chronic and degenerative diseases.

The company’s technology is based on a library of microbial strains collected from healthy human donors. From this library, Seres uses computational techniques to identify microbial communities in the gut associated with healthy and diseased states, then zeroes-in on specific microorganisms, which in the right combinations, can restore healthy functions in the gut from a state of dysbiosis. The company purifies these target microbial combinations into therapy candidates for testing in lab cultures and animal models, and later in clinical trials.

For cancer immunotherapy, Seres has an option to license the rights to discoveries at MD Anderson, part of the University of Texas system, involving gut bacteria combined with cancer immunotherapies. Much of MD Anderson’s work in this field is done by Jennifer Wargo, who studies immunotherapy, particularly for melanoma, an aggressive form of skin cancer. In a paper published in Science magazine earlier this month, Wargo and colleagues tested fecal samples of melanoma patients undergoing immunotherapy targeting PD-1 proteins, known as checkpoint proteins, on T-cells in the immune system. These checkpoint inhibitors are designed to block the binding actions of PD-1 proteins, enabling T-cells to produce an immune-system response against cancer cells.

The researchers found melanoma patients who responded to immunotherapy treatments had a different gut microbe composition than patients that did not respond. Responding patients, for example, had a more diverse set of gut microbes, and while the responding patients’ microbial communities were not identical, they more often showed the presence of Ruminococcaceae bacteria than non-responders. These are common gut microbes that break down complex carbohydrates. Fecal transplants of responders’ gut microbes into lab mice also produced higher anti-tumor immunity.

“Immunotherapy has represented an important advance for melanoma and other cancers,” says Wargo in a joint statement. “However, in the majority of patients, the response is not adequate to durably control disease. Modulation of the microbiome is a promising approach that may improve the therapeutic benefit of checkpoint therapy.”

Seres is developing an oral therapy harnessing the microbiome code-named SER-401, now in preclinical testing. SER-401, says the company, is designed to boost the effectiveness and safety of anti-PD-1 checkpoint inhibitors with a specific collection of gut bacteria. The joint project includes a placebo-controlled clinical trial evaluating SER-401 among patients with advanced metastatic melanoma.

The Parker Institute is a foundation-supported consortium of immunologists and cancer specialists at academic cancer centers, including MD Anderson, that seeks to accelerate development of cancer therapies harnessing the immune system.

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