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Gene-Edited Treatments in Works for Safer Cancer Therapies

T-cells and cancer cells

Killer T-cells surround a cancer cell (NICHD, Flickr)

13 Sept. 2021. A cancer center and biotechnology enterprise are developing gene-edited therapies working in the gut to reduce adverse effects from cancer immunotherapies. The project brings together M.D. Anderson Cancer Center, part of the University of Texas system in Houston, and the company Snipr Biome in Copenhagen, Denmark.

M.D. Anderson and Snipr Biome aim to validate gut microbe targets and design therapies with the gene-editing technique Crispr that reduce adverse intestinal effects of immune checkpoint inhibitors, a type of immunotherapy for cancer. Immune checkpoint inhibitors block the ability of cancer cells to turn off the immune system, allowing T-cells in the immune system to attack tumors. While checkpoint inhibitors are effective in some forms of cancer, they also are associated with inflammatory bowel diseases, such as colitis, in patients receiving the therapy.

In a study published in July in Nature Medicine, a team led by Jennifer Wargo, professor of genomic medicine and surgical oncology at M.D. Anderson, found about about half of melanoma patients treated with immune checkpoint inhibitors that the team assessed, experienced severe or life-threatening adverse effects. The researchers went on to identify two specific types of gut bacteria produced in patients receiving immune checkpoint inhibitor therapies, who also developed colitis. The cancer therapies addressed CTLA-4 and PD-1 proteins often targeted by immune checkpoint inhibitors.

Snipr Biome develops therapies addressing gut microbes using the gene editing technology Crispr, short for clustered regularly interspaced short palindromic repeats. Crispr is a genome-editing process based on bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA. The company’s technology selectively delivers edited DNA killing harmful gut bacteria, like an antibiotic, or preventing bacterial infection. Snipr Biome says its Crispr process can also edit DNA to add genes coding for therapeutic proteins or peptides.

Regulate gut microbes to reduce toxicity

Snipr Biome says it uses Crispr’s RNA-guiding property to deliver therapies, either with bacteriophages, a type of virus that infects bacteria, or bacterial conjugation, where one organism transfers material to another through direct contact. The company says it can deliver therapies as oral drugs, injections, or through the skin.

“Treatment with immune checkpoint inhibitors and other forms of immunotherapy,” says Wargo in an M.D. Anderson statement, “has dramatically improved outcomes for patients with cancer, but these therapies can cause significant side effects. Microbes within the gut of patients have been shown to influence responses to immunotherapy, and we now have evidence that they can impact toxicity as well.”

Snipr Biome and M.D. Anderson first plan to validate microbiome targets associated with immune-related adverse effects from immune checkpoint inhibitors. The project team will then develop therapies for regulating gut microbes to reduce toxicity of those therapies. The parties expect to conduct preclinical studies, but also note the potential for a clinical trial. Financial and intellectual property terms of the agreement were not disclosed.

M.D. Anderson is conducting the work under its Program for Innovative Microbiome and Translational Research, or Prime-TR, that studies microbial communities in the body for ways to improve cancer prevention, diagnosis, and treatment. Wargo is director of Prime-TR.

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