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Research Using Bacteria to Treat Cancer

The possibility of giving microbes in the future (whether bacteria, viruses, or fungi) to treat cancer is amazing. Of course big pharma is pursuing this line of research, which is called immunotherapy (stimulating the body's ability to fight tumors). The Bloomberg Business article discusses a number of big pharma companies entering the field and their main focus. The study in the journal Science finding that giving common beneficial bacteria (Bifidobacterium breve and Bifidobacterium longum) to mice to slow down melanoma tumor growth is a first step. The researchers themselves said that the 2 common beneficial bacteria species exhibited anti-tumor activity in the mice and was as effective as an immunotherapy in controlling the growth of skin cancer. But note that the bacteria needed to be live. Stay tuned....

From Bloomberg News: How Gut Bacteria Are Shaking Up Cancer Research

Top scientists at Roche Holding AG and AstraZeneca Plc are sizing up potential allies in the fight against cancer: the trillions of bacteria that live in the human body. "Five years ago, if you had asked me about bacteria in your gut playing an important role in your systemic immune response, I probably would have laughed it off," Daniel Chen, head of cancer immunotherapy research at Roche’s Genentech division, said in a phone interview. "Most of us immunologists now believe that there really is an important interaction there."

Two recent studies published in the journal Science have intrigued Chen and others who are developing medicines called immunotherapies that stimulate the body’s ability to fight tumors.In November, University of Chicago researchers wrote that giving mice Bifidobacterium, which normally resides in the gastrointestinal tract, was as effective as an immunotherapy in controlling the growth of skin cancer. Combining the two practically eliminated tumor growth. In the second study, scientists in France found that some bacterial species activated a response to immunotherapy, which didn’t occur without the microbes. 

That’s increased drugmakers’ interest in the human microbiome -- the universe of roughly 100 trillion good and bad bacteria, fungi and viruses that live on and inside the body. Roche is already undertaking basic research in the field and plans to investigate the microbiome’s potential for cancer treatment, Chen said."Certainly, we are already scanning the space for interesting opportunities as the science continues to emerge," he said. "We are very interested in testing these in a controlled setting."

Another startup, 4D Pharma Plc, in November said it had discovered a bacterium that produces a response comparable to that of an immunotherapy in animal tests for breast and lung cancers. The London-listed company plans to start trials in patients by the end of this year. To support research in autoimmune and neurological diseases, in addition to cancer, the company has raised over 100 million pounds ($140 million) from investors over the last two years, CEO Duncan Peyton said in a phone interview.

"We are in active discussions with the usual suspects in the immunotherapy space," Belichard said in an interview in London. Those active in the field include a wide range of pharma companies including AstraZeneca, Roche, Bristol-Myers Squibb Co., and Merck & Co....The sheer number of bacteria, some of which could actually switch off an immune response, and the question of how much bacteria is needed, make it a complex area of research, Roche’s Chen said. It’s possible that the same bacteria could induce both harmful and helpful responses, depending on the patient, he said. Still, "it’s one of the most interesting developments we’ve seen in science over the last several years," he said.

The Abstract and excerpts of the article in the journal Science: Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy.

T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8(+) T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.

Bifidobacterium-treated mice displayed significantly improved tumor control in comparison to non-Bifidobacterium treated counterparts which was accompanied by robust induction of tumor specific T cells in the periphery and increased accumulation of antigen -specific CD8+T cells within the tumor. These effects were durable for several weeks....Heat inactivation of the bacteria prior to oral administration also abrogated the therapeutic effect on tumor growth and reduced tumor-specific T cell responses to baseline, suggesting that the antitumor effect requires live bacteria. As an alternative strategy, we tested the therapeutic effect of B. breve and B. longum strains obtained from the ATCC, which also showed significantly improved tumor control.... Oral administration of Lactobacillus murinus to TAC mice, which was not among the overrepresented taxa in JAX (Jackson Laboratory)-fed mice, had no effect on tumor growth or on tumor-specific T cell responses, suggesting that modulation of antitumor immunity depends on the specific bacteria administered. Collectively, these data point to Bifidobacterium as a positive regulator of antitumor immunity in vivo.

Our studies demonstrate an unexpected role for commensal Bifidobacterium in enhancing antitumor immunity in vivo. Given that beneficial effects are observed in multiple tumor settings, and that alteration of innate immune function is observed, this improved antitumor immunity could be occurring in an antigen-independent fashion. The necessity for live bacteria may imply that Bifidobacterium colonizes a specific compartment within the gut that enables it to interact with host cells that are critical for modulating DC function, or to release soluble factors that disseminate systemically leading to improved DC function.

Bifidobacterium longum. Courtesy of Mark Schell, Univ.of Georgia

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