Pushing cancer immunotherapy forward
Saman Maleki, PhD, is combining the strength of the microbiome and the immune system to boost our body’s natural ability to fight cancer
By Crystal Mackay, MA’05
In Saman Maleki’s bright office, three floors above the London Regional Cancer Program, shelves are cluttered with books on oncology and the immune system – an expected collection for a researcher who studies how the power of the immune system can be harnessed to more effectively treat cancer.
But it’s the poop emojis that draw attention, including the large, stuffed version he displays prominently during Zoom calls.
“People just keep buying me poop emoji gifts,” he said with a laugh. “My wife even ordered me a big poop emoji cake for my birthday.”
He enjoys the humour in the cartoon eyes and friendly smile, but for Maleki, PhD’14, Assistant Professor, Oncology, this cheeky emoji represents something far more serious. It is the symbol of the way forward in his cancer immunotherapy research, a gateway to boosting the power of immunotherapy and potential key to why some people respond to this treatment when others don’t.
His latest research focuses on modifying patients’ gut microbiome, through fecal (poop) transplants, from healthy donors to improve the effectiveness of immunotherapy in skin and kidney cancer patients before they receive their therapy.
“We think it provides a boost to the immune system to further help the drug do its work. The beauty of the microbiome is that we can change it in the gut, and you can generate a systemic response in the immune system that can target a tumour anywhere else in the body, which is remarkable,” said Maleki.
“There will always be setbacks, and people who don’t see things the way you do, but that doesn’t mean you should quit. Our lab motto is, ‘people who say it can’t be done should never interrupt those who are doing it.’”
— Saman Maleki, PhD’14
Maleki’s interest in immunotherapy began while completing his PhD research at Schulich Medicine & Dentistry. It has always been his belief that there needs to be close collaborations between scientists and clinicians, and so he designed his own training program to be sure he could spend time with clinicians and medical fellows to understand their challenges and successes in the clinic and how that might be reverse translated to the lab. It was during that time that the world’s first cancer immunotherapy drug was approved for use.
Called Ipilimumab, it is the first member of a class of drugs known as check-point inhibitors, and works by taking the brakes off the immune system in order to ramp up its power to fight cancer. Our immune system already has a natural ability to seek out and destroy tumour cells and does so on a daily basis.
“This drug demonstrated that we didn’t need to push the immune cells to remove cancer, we just needed to remove the brakes from them to let them do their job,” he said.
With the field just starting to re-emerge during his graduate training, he was often scoffed at and even laughed at when he talked about the power of immunotherapy with his colleagues. But this only made him more determined to demonstrate that it could work.
“There will always be setbacks, and people who don’t see things the way you do, but that doesn’t mean you should quit,” he said. “Our lab motto is, ‘people who say it can’t be done should never interrupt those who are doing it.’”
By learning everything he could about the field and spending time following physicians and practitioners in the cancer centre, Maleki quickly realized that while immunotherapy seemed to work wonders for some patients – shrinking their tumours almost completely with a long-lasting effect – it had little to no effect on others, with no real explanation as to why.
“As amazing as these drugs are, and they have been life-changing for a lot of patients, they still don’t work in everyone,” he explained. This was the spark that moved his research forward, as he began to investigate ways to increase the response rate for all patients.
He is currently doing that in two ways: through a method that instigates DNA damage in the tumour cells to make them more visible to the immune system; and fecal transplants into patients from healthy donors, an idea Maleki dreamt up when the literature started to show that patients who responded more effectively to immunotherapy had more diverse gut microbiomes than those who didn’t.
Researchers were able to show that if they took the microbiome from the patients that responded well and those who did not, and transplanted into a mouse model of cancer, immunotherapy only worked in the mice with the fecal transplants from responders.
He again had to convince his colleagues in the field that this was a worthwhile line of research to pursue in patients. He and his team are now one of the first in the world to try this same approach in humans. Early results are showing that they’ve been able to more than double the clinical benefit of the drug in the patients who had the transplanted microbiome.
“That is the most incredible part for me because I had this vision five years ago and I can see today that it is actually helping patients,” he said. “You can always learn from those who criticize you, but you never want to lose sight of where you are going.”
