Engineered bacteria prime solid tumors for immunotherapy

Human T cell
An engineered, non-pathogenic bacterium armed with a cancer-fighting antibody primed immune-boosting T cells to attack solid tumors in mice. (NIAD)

Arming the immune system so it can recognize and attack cancer is now a proven strategy for success in fighting some forms of the disease, notably blood cancers. But immunotherapy for solid tumors has proven to be elusive.

Scientists at Columbia University hope to change that, using another emerging field of science: synthetic biology. A team at Columbia Engineering and the university’s Irving Medical Center are engineering bacteria that can deliver immunotherapy drugs straight to solid tumors.

In mice, the strain of bacteria that the researchers made was able to set up shop in the tumors they were injected into, releasing drugs from within that killed the cancer locally. The treatment also spread to distant tumors, slowing down cancer metastasis. The researchers published their findings in the journal Nature Medicine, and they’ve set up a company to develop the technology for use in people.

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The bacterium that the researchers developed is a non-pathogenic strain of E. coli. It’s designed to colonize solid tumors, replicating until the number of bacteria reaches a certain threshold. Then the bacteria self-destructs, releasing anti-cancer therapeutics in the tumors. A small number of bugs survive—enough to continuously deliver the drug.

The Columbia researchers first described the engineered bacteria in 2016, and for this experiment, they wanted to add a drug payload. So they attached a tiny antibody that targets CD47, a protein that normally shields cancer cells from immune attack. CD47 is present in many types of solid tumors.

“But CD47 is present elsewhere in the body, and systemic targeting of CD47 results in significant toxicity,” said lead author Sreyan Chowdhury, a Ph.D. candidate at Columbia, in a statement. “To solve this issue, we engineered bacteria to target CD47 exclusively within the tumor and avoid systemic side-effects of treatment.”

RELATED: AstraZeneca taps microbiome specialist Seres for I-O support

The engineered bacteria proved adept at “priming” tumor-specific T cells from the immune system to treat the primary tumor, and to travel to distant tumors, the Columbia team reported. The treatment cleared primary tumors in mice and reduced metastasis.

The potential role of bacteria in boosting cancer immunotherapy is an area of interest in the oncology research community, and some biopharma companies are investing significant resources in this emerging field of study. In March, for example, AstraZeneca laid out $20 million to collaborate with Seres Therapeutics on its microbiome-based drug, SER-401. It’s designed to modify the gut bacteria of cancer patients to boost the efficacy of immunotherapy, and the two companies plan to combine it with drugs that inhibit immune checkpoints.

Evelo Therapeutics teamed up with the Mayo Clinic in 2016 to build a library of gut bacteria that boost the immune response to cancer and use some of them to develop new therapeutics. Last year, Evelo pulled in more than $76 million in an initial public offering, which it is using to develop its lead candidate to treat melanoma.

In April of this year, a global research consortium led by Sanford Burnham Prebys said it identified 11 bacterial strains in the gut microbiome that unleashed a strong immune response to melanoma.

The next step for the Columbia team is to design studies to further prove out its strategy of attaching a cancer-fighting nanobody to engineered E. coli. The researchers are also planning safety studies in a range of solid tumors, which could lead to clinical trials in people.

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