Fecal microbiota transplants show promise in improving response to immunotherapy for melanoma

In a groundbreaking clinical trial published in the prestigious journal Nature Medicine, researchers from Lawson Health Research Institute, the Centre hospitalier de l’Université de Montréal (CHUM), and the Jewish General Hospital (JGH) have made a significant discovery. They found that fecal microbiota transplants (FMT) from healthy donors can be safely used and hold promise in enhancing the response to immunotherapy in patients with advanced melanoma.

Immunotherapy drugs work by stimulating a person’s immune system to target and eliminate cancer cells. While these drugs have shown remarkable improvements in survival rates for melanoma patients, they are only effective in around 40 to 50 percent of cases. Early research indicated that the human microbiome, which comprises a vast array of microorganisms in our bodies, may play a role in determining whether a patient responds positively to treatment.

Dr. John Lenehan, a Medical Oncologist at London Health Sciences Center’s (LHSC) London Regional Cancer Program (LRCP), Associate Scientist at Lawson, and Associate Professor in the Department of Oncology at Western University’s Schulich School of Medicine & Dentistry, explained the objective of the study: “In this study, we aimed to enhance melanoma patients’ response to immunotherapy by improving the health of their microbiome through fecal transplants.”

A fecal transplant involves the collection of stool from a healthy donor, which is then carefully screened and processed in a laboratory before being transplanted into the patient. The goal is to introduce the donor’s microbiome, allowing beneficial bacteria to thrive in the patient’s gut.

Dr. Saman Maleki, a Scientist at Lawson and LHSC’s LRCP, Assistant Professor in Schulich Medicine’s Departments of Oncology, Pathology and Laboratory Medicine, and Medical Biophysics, and senior investigator on the study, emphasized the significance of the microbiome-immune system-cancer treatment connection: “The relationship between the microbiome, the immune system, and cancer treatment is an emerging field of scientific inquiry. This study aimed to leverage microbial communities to improve outcomes for patients with melanoma.”

The phase I clinical trial involved 20 melanoma patients recruited from LHSC, CHUM, and Jewish General Hospital. These patients received approximately 40 fecal transplant capsules orally during a single session, one week before commencing their immunotherapy treatment.

This groundbreaking research provides hope for improving the effectiveness of immunotherapy for melanoma patients. By harnessing the potential of fecal microbiota transplants to enhance the health of the microbiome, scientists have taken an important step toward advancing cancer treatment options.

Dr. Saman Maleki and Dr. John Lenehan discuss the results of their recent study on fecal transplants for advanced melanoma patients. Credit: Lawson Health Research Institute

In a significant phase I clinical trial, researchers have successfully demonstrated the safety and potential efficacy of combining fecal transplants with immunotherapy for melanoma patients. The primary objective of this trial was to assess the safety of the treatment, and it was found to be safe for patients. Additionally, an encouraging 65 percent of patients who retained the donors’ microbiome exhibited a clinical response to the combination therapy. However, it is worth noting that five patients experienced adverse events commonly associated with immunotherapy, leading to the discontinuation of their treatment.

Dr. Bertrand Routy, Oncologist and Director of CHUM’s Microbiome Center, expressed the potential impact of this study, stating, “We have reached a plateau in treating melanoma with immunotherapy, but the microbiome has the potential to be a paradigm shift.” This research places Canada at the forefront of microbiome research, highlighting the ability to enhance patients’ response to immunotherapy through fecal transplants.

Dr. Wilson H. Miller Jr. of the JGH and Professor in the Departments of Medicine and Oncology at McGill University echoed the significance of these findings, stating that they contribute to the growing body of evidence supporting the idea that targeting the microbiome could be a major advancement in utilizing immunotherapy for cancer patients.

One unique aspect of this study is the administration of fecal transplants in capsule form to cancer patients, a technique pioneered by Dr. Michael Silverman, a Lawson Scientist, Chair of Infectious Diseases at Schulich Medicine, and Medical Director of the Infectious Disease Care Program at St. Joseph’s Health Care London. Dr. Silverman’s team has been conducting fecal transplants for 20 years, initially focusing on successfully treating C. difficile infections. Their expertise in this field allowed them to develop highly effective methods, resulting in a high rate of donor microbes surviving in the recipient’s gut with just a single dose. The efficacy of the capsules is believed to contribute to the success observed in melanoma patients.

Building on these promising results, the research team has initiated a larger phase II trial involving multiple centers in Ontario and Quebec. Furthermore, Lawson researchers are exploring the potential of fecal transplants in treating other types of cancer, such as renal cell carcinoma, pancreatic cancer, and lung cancer, as well as studying its potential in managing HIV and rheumatoid arthritis.

Source: Lawson Health Research Institute

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