窪蹋勛圖厙

 

Channeling the power of natural killer cells to beat cancer

- June 17, 2024

Pancreatic cancer is one of the most difficult cancers to treat successfully, and one of the chief targets of the natural killer cell research Dr. Jeanette Boudreau and her graduate students and post-doctoral fellows pursue. (Provided photo)
Pancreatic cancer is one of the most difficult cancers to treat successfully, and one of the chief targets of the natural killer cell research Dr. Jeanette Boudreau and her graduate students and post-doctoral fellows pursue. (Provided photo)

When Dr. Jeanette Boudreau envisions the future of treating pancreatic, ovarian, and colorectal and cancers that are difficult to cure, she cant contain her excitement.

Dr. Boudreau, an immunologist and the scientific director of the Beatrice Hunter Cancer Research Institute, is pinning her hope and her knowledge on Natural Killer (NK) cells. These white blood cells, which circulate constantly through the bloodstream and tissues, eliminate viral infections and sick cells, including cancer cells.

Dr. Boudreaus research focuses on how to aim those cells at specific types of hard-to-treat cancers, super-charging the immune system to recognize the signals these tumours emit and then destroy them.

The way I see the future, there are vats of these things being made, and in the same way you (now) order up platelets or red blood cells for a transfusion, an oncologist could order up NK cells for therapy, says Boudreau, who is also an associate professor and Cameron cancer scientist at Dalhousie.

This is obviously down the road, but thats the space I am hoping we land in.

Killing pancreatic tumours


Pancreatic cancer is one of the most difficult cancers to treat successfully, and one of the chief targets of the natural killer cell research Dr. Boudreau and her graduate students and post-doctoral fellows pursue.

PhD candidate Stacey Lee, who studies in Dr. Boudreaus lab, has already demonstrated that NK cells can kill pancreatic cancer tumours. She has also created a mouse model with human tumours, which she can treat with human NK cells.

Lees work creates a living system the researchers can study. Thanks to her model, Lee has identified four proteins from pancreatic tumours she believes she can treat with NK cells creating the foundation for more precise immunotherapy.

Using donated tissue samples from patients undergoing surgery, a second PhD student, Riley Arseneau, identifies genetic mutations in the tumours of those surgery patients. Shes also identifying the genomic and genetic sequences of people in the Maritimes who come to Halifax for pancreatic cancer treatment.

Identifying those mutations is important. A small percentage of people with two types of gene mutations, called BRCA 1 and BRCA 2, respond better to a drug called cisplatin than they do to the usual chemotherapy cocktail for pancreatic cancer.

If Arseneau can also identify additional, rarer mutations in peoples tumours, the information will help doctors plan treatments that will work better for each individual.

Identifying mutations specific to the Maritime population will guide the type of precision therapy each patient would receive, Dr. Boudreau says.

Dr. Boudreau, Lee, Arseneau, and other team members are also building model systems of pancreatic tumours. Theyre gathering evidence to make the case that everyone diagnosed with pancreatic cancer should automatically have their tumours analyzed genetically.

That analysis would help to identify the best approach to treatment, using chemotherapy that is already available here.

This type of precision medicine does not require a clinical trial to implement it could be happening now, Dr. Boudreau emphasizes.

Our genetics arent informing [pancreatic cancer] treatment today, but they could be tomorrow, if we can just say this is the difference you could make, she says.

Once Dr. Boudreau and her colleagues understand the genetics of the Maritime population and the role NK cells can play in tackling pancreatic and other types of cancer, they can design new genetic-based therapies.

Demolishing ovarian cancer cells


Ovarian cancer is another focus of researchers in Dr. Boudreaus lab. PhD students Sarah Nersesian and Morgan Pugh-Toole, alongside MSc student Anna Nicolela, are determining ways to get natural killer cells to demolish ovarian cancer cells. This team shares their observations with Emily Carter, an MSc student, who is figuring out how to make large numbers of NK cells. Shes using Lees mouse model to test her hypotheses.

A good chunk of my lab is working on NK-cell based therapies for ovarian cancer, focusing a lot on the way the NK cells direct the rest of the immune system to interact with the tumors, Dr. Boudreau says.

New therapies using NK cells are five to 10 years in the future for hard-to-treat tumours like those in ovarian cancer, Dr. Boudreau estimates. But in other diseases, like pancreatic cancer, it may be possible to help at least a proportion of patients by implementing gene sequencing right away, she says.

One of Dr. Boudreaus critical roles is to work with patient partners, oncologists and other clinicians treating patients with cancer, to bring all parties the latest developments in immunotherapy research and treatment advances.

The clinicians Dr. Boudreau works with are eager to learn about and translate the discoveries researchers have made.

Weve got some really fantastic partnerships that we have formed, Dr. Boudreau says.

Meanwhile, she focuses on making a difference in peoples lives today, even as she also moves the dial on research that will deliver better outcomes tomorrow.

Im trying my best to do things on a scale that could be implemented, are not too expensive, and could be done with the processes that already exist, as patients are already being treated, says Dr. Boudreau.

The research Dr. Boudreau and her team is vital. Although immunotherapy is quickly becoming a mainstay of cancer treatment, its expensive and can be challenging to deliver, she points out.

We think with NK cells we can make a scalable, much more affordable immunotherapy, so we can treat more patients.