Fighting cancer with living drugs
Originally published in The Queen's Gazette. Cell therapy is changing how we treat cancer, and Annette Hay is working at the forefront of this very big wave.
When Annette Hay was in medical school in Scotland in the early 2000s, cell therapy wasn’t even a topic in the curriculum. In 2019, she saw it save the life of young man with leukemia who had exhausted every other option.
“He was in his early twenties, and he was about to die of his disease. We’d tried everything we knew how to do, and nothing was working,” says Dr. Hay, Associate Professor in the Queen’s Department of Medicine and Senior Investigator with the Canadian Cancer Trials Group. “We managed to get cell therapy for him, and now he is in remission and getting on with life.”
While Dr. Hay was already interested in cell therapies by this time, this remarkable clinical turnaround focused her attention on the promise of this rapidly developing method of treatment. At the same time, the story also illustrated how far cell therapy still needs to go to reach its full potential, as the young man nearly died waiting a month for the engineered cells to arrive from the United States.
Dr. Hay saw the opportunity for a new system to advance cell therapies and get them to patients much sooner. She began discussions with colleagues across the country and, along with Jonathan Bramson of McMaster, established ExCELLirate Canada. This newly formed network brings together existing expertise from organizations and individuals across Canada so they can leverage each others’ resources, coordinate efforts, identify gaps, and fill them. ExCELLirate Canada’s goal is to develop and test new cell therapies and create an economic framework to make them more accessible.
One of Dr. Hay’s roles in ExCELLirate Canada is to help organize clinical trials in cell therapy through the Canadian Cancer Trials Group (CCTG), a Queen’s-based cooperative oncology organization with an expansive network of investigators.
The Queen’s Gazette recently connected with Dr. Hay to learn more about cell therapy and the ways in which microscopic “living drugs” could soon lead to sweeping changes in how we treat cancer. In the not-too-distant future, according to Dr. Hay, the body’s own cells – rather than treatments like surgery or chemotherapy – could become the frontline defense against the disease.
Let’s start with the basics. What is cell therapy and how does it work?
It’s a revolutionary way of treating cancer by using the body’s own immune system. The specific form of cell therapy we use now is called CAR T-cell therapy, short for Chimeric Antigen Receptor T-cell therapy. It starts by taking a patient’s own blood cells — their lymphocytes — and engineering them to make them recognize the cancer. Then you produce millions of the enhanced cells and infuse them back into the patient so they can kill the cancer cells. That engineering is an involved process, because you’re essentially manufacturing a living drug. This kind of cellular engineering can only be done in a biomanufacturing factory set up to do it, and there’s a limited number of those in North America.
It sounds like cell therapy has come a long way in a short period of time. How has the field evolved in recent years?
It’s evolved incredibly quickly. Effectively, it didn’t exist even ten years ago. Over the last three or four years it went from something that we started to hear about in clinical trials to being an established, funded standard of care for people in Canada who have certain types of leukemia and lymphoma. There are three cell therapy products that are available in Canada, and one more is expected imminently. And there are hundreds of clinical trials testing lots of different types of cell and gene therapy products in cancer as well as other diseases, such as HIV, sickle cell anemia, and hemophilia. While the currently approved cell therapies only work against blood cancers, it’s only a matter of time until we learn how to use the method to fight against solid tumours as well. So, it’s exploding now. I feel as if we’re still at the start of a very big wave.
Now that ExCELLirate Canada is off the ground, what role are you and the Canadian Cancer Trials Group (CCTG) playing in the development of new cell therapies?
Other organizations and individuals in the network bring expertise in biomanufacturing and the discovery of novel therapies. We specialize in clinical trials, and we are developing multi-centre clinical trials that incorporate the expertise of the entire ExCELLirate Canada network. CCTG is uniquely positioned to lead these complex collaborative trials with the established investigator network across Canada and internationally. No other organization in the country has the same scope and track record.
You say you want the ExCELLirate team to address the challenges that are preventing cell therapies from being used to their full potential. What are some of those challenges?
There are two different sets of challenges, those we’re facing right now and those we’ll face in the future. Right now, we need to make sure that as many people as possible who may benefit from the approved products can get them. There are a few things standing in the way of reaching that goal. It’s a mix of cost, hospital capacity, and time.
Right now, it costs around $400,000 (USD) for a dose of CAR T-cells. If the price tag stays there, it is never going to reach its full potential. There’s also more demand for cell therapy than there is capacity to provide it. It can take more than a month to secure a manufacturing slot and make the cells patients need, and they sometimes die waiting for the treatment. We need to deliver the therapies more efficiently in order for patients to receive the full benefits.
The delays and costs are compounded by the fact that most people have to travel to access cell therapies. Patients used to have to travel to the United States for treatment but now you can usually go to Ottawa or another city in Canada. But we’re working to expand the number of places you can receive cell therapy even further. Locally, we’re working to establish Kingston Health Sciences Centre as an approved centre for CAR T-cell therapy, so we can treat our own patients here. We’re aiming to have this completed by the end of 2023.
For the future, we need to prepare to scale up for the tsunami of demand that’s coming.
What do you think the future of cell therapy could look like?
This field is evolving so quickly, nobody knows what it will look like even ten years from now. But it is definitely here to stay. It is a whole new way of approaching cancer. It’s going to expand. We’ll be continually finessing the products patients use to make them more effective and safer. So, we probably won’t be using the treatments we’re using today ten years from now.
If cell therapy reaches its full potential, we’ll see it available to patients with a wide variety of cancers, achieving meaningful clinical responses – ideally, cures. I would love to see it become affordable enough to be widely available in developing countries, not just wealthy ones.
I think cell therapy will expand beyond cancer and become an effective treatment for numerous other conditions, including hereditary conditions, autoimmune conditions, and infections.