Inside Dr. Saman Maleki’s lab on the fourth floor of LHSC’s Verspeeten Family Cancer Centre, cutting-edge immuno-oncology research is exploring how fecal transplants (yes, poop transplants!) can improve the effectiveness of cancer treatment. It’s called fecal microbiota transplantation (FMT), a treatment that targets the gut microbiome – the bacteria, fungi, and viruses that naturally live inside our bodies. By tweaking this microbial community, FMT can shift the bacteria that protect tumours, making cancer treatments like immunotherapy and chemotherapy more effective.
The process involves taking stool from healthy donors, processing it in a lab, and providing it to patients in tasteless, odourless capsules. These capsules were pioneered and are developed right here in London, Ontario by Dr. Michael Silverman’s team at Lawson Research Institute of St. Joseph’s Health Care London.
From the bench to beside
In the photos below, Dr. Maleki, Scientist at London Health Sciences Centre Research Institute (LHSCRI), takes us into his lab, showcasing how his team’s research is transforming lab results into clinical trials and improving cancer therapies. His out-of-the-box thinking and visionary approach to cancer treatment using FMT are pushing the boundaries of science, offering researchers worldwide a promising new avenue in the fight against cancer.
Most of Dr. Maleki’s projects are translational in nature, meaning they focus on analyzing patient samples being treated in clinical trials that he’s co-leading with his oncology and St. Joseph’s colleagues. These studies aim to better understand what is happening with the patients’ immune system and gut microbiome as they receive cancer treatments. Dr. Maleki – who was named 2024 Researcher of the Year by Western University’s Schulich School of Medicine & Dentistry – closely monitors the experimental progress of these projects in the lab, observing how cancer cells respond to treatment.
Above: In the microscope, Dr. Maleki observes cancer cells and how they have responded to treatment.
About 10 years ago, Dr. Maleki and his colleagues started exploring the potential of FMT to boost the effectiveness of cancer therapies, and the results have been groundbreaking. In 2023, Dr. Maleki, along with scientists from Lawson Research Institute, Centre Hospitalier de l’Université de Montréal, and Lady Davis Institute of the Jewish General Hospital, published a world-first study involving 20 patients with advanced melanoma, which was featured by CBC News. Typically, 30 to 40 per cent of melanoma patients respond to immunotherapy. However, in this phase I trial, 65 per cent of those who received stool capsules showed an improved response to immunotherapy, with cancer becoming completely undetectable in four patients.
Testing cancer therapies in preclinical models
Biomedical research will only advance when scientists in the lab gain a deep understanding of what occurs in the body when treating patients. This knowledge is crucial for developing new therapies. To help Dr. Maleki understand the impact of patients’ microbiomes on cancer treatment, his research team conducts studies using preclinical cancer models.
They introduce a patient’s microbiome and tumour into the preclinical models, creating a model that mimics the patient’s condition. They then test the same treatment the patient received. The team isolates immune cells from tumours in these models, as these cells play a critical role in fighting diseases like cancer, and study how changes in the microbiome affect the immune cells’ ability to respond to immunotherapy.
Above (from left to right): Dr. Maleki oversees experiments in the laboratory with members of his research team: Tiffany Cheung, Master of Science student; Rene Figueredo, Research Assistant, lead technician and lab manager; and Chloe Davidson, Master of Science student.
Analyzing data
Dr. Maleki and his bioinformatics team analyze and discuss data generated from clinical trials. They monitor patients’ gut microbiome data and track how it changes over time following fecal transplants and immunotherapy. Patients who experience better integration of their donor’s microbiome from fecal transplants tend to respond more favourably to immunotherapy.
In the photos below, Dr. Maleki examines the features of immune cells inside lymph nodes near a tumour, which was isolated from a preclinical study. He is working to understand how changing the tumour environment impacts immune cells both within the tumour and in the nearby lymph nodes, where immune cells get activated to target tumour cells.
Above: Dr. Maleki examines data with Behnam Jabbarizadeh, Research Data Analyst.
Recruiting patients and discussing treatment plans
Patients from across southwestern Ontario are recruited to clinical trials at London Health Sciences Centre Research Institute (LHSCRI) or other centres in Canada when participating in multi-centre trials led by LHSCRI. For many cancer patients, the motivation to participate in these clinical studies extends beyond the hope of benefiting from the treatments — they are also driven by a desire to help future patients.
In the photos below, Dr. Maleki discusses a patient’s treatment plan with his clinical fellow, Dr. Danial Hadi. Dr. Hadi is currently recruiting pancreatic cancer patients for an ongoing FMT clinical trial at LHSCRI and Lawson. Common treatment plans often involve a combination of two immunotherapy drugs, chemotherapy, or a combination of chemotherapy and immunotherapy, depending on the type of cancer.
Above (from left to right): Dr. Maleki discusses treatment plans with clinical fellow Dr. Danial Hadi and patient recruitment with Clinical Research Assistant, Sophie Harris.
What’s next?
In another world-first study, Dr. Maleki and his colleagues are investigating the potential of FMT to enhance chemotherapy for patients with advanced pancreatic cancer. The research team will test the treatment in 20 cancer patients from the Baker Centre for Pancreatic Cancer, which is part of Verspeeten Family Cancer Centre at LHSC. The goal is to determine whether a successful shift in the gut microbiome can lead to a better response to chemotherapy.
Building on positive results from the study with melanoma patients, Dr. Maleki and the research team at the Canadian Cancer Trials Group have also launched one of the world’s largest randomized clinical trials to explore how FMT can improve outcomes for patients with advanced melanoma.
Their research is giving new hope to patients worldwide and paving the way for the next generation of microbiome-based therapies in oncology. As the team expands its studies, the future of cancer treatment looks brighter, with FMT emerging as a potentially transformative approach to improving patient outcomes and survival rates.