Canada is working on the next generation of cancer treatment for those who have no other options.

Chimeric Antigen Receptor modified T-Cells (CAR-T) is a new treatment approved by the U.S. Food and Drug Administration (FDA).  BioCanRx a not for profit network of scientists, clinicians, academic institutions, NGO's and industry partners are working to create the capacity in Canada to treat patients using CAR-T cell therapy. 

Medical Oncologist blood specialist and Head of the Medical Oncology Department at Cancer Care Manitoba Dr. Matthew Seftel explain why this treatment is a big step in cancer care for Manitoba.

"We already have an existing and sophisticated stem-cell and bone-marrow program right here in Winnipeg. Once the product which was recently approved in the U.S. becomes licensed for use in Canada, we would be more than enthusiastic to try and introduce that treatment locally to Manitobans."

CAR-T therapy is the process of taking the body’s immune cells or T-cells and genetically modifying them to attack a specific marker. These markers are proteins found in leukemia and lymphomas when the T-cells locate these markers they attack and destroy it.

Image used with permission from Rockland Immunochemicals, Inc. A typical CAR T cell therapy involves four basic steps. (1) A patient or donor is leukapheresed to isolate peripheral blood mononuclear cells (PBMCs). (2) These cells are manipulated to express CAR by gene transfection. (3) CAR-expressing cells are differentiated into effector immune cells and expanded to sufficient number in vitro. (4) The CAR effector cells are then introduced into the patient. This is frequently done in conjunction with either chemo- or radiotherapy.
The CTL019 (tisagenlecleucel) r/r B-Cell ALL program approved in the U.S., uses CAR-T therapy, to treat patients with relapsed or refractory(r/r) ALL in pediatric and young adult patients.

Local oncologist Dr. Cornie Woelk, Medical Director for the Boundary Trails Regional Cancer program explains more about The CTL019 (tisagenlecleucel) program.

BioCanRx is looking to find feasible cost-effective methods of making CAR-T therapy available to Canadians, comparable to obtaining the resources for a bone marrow transplant

Currently, CTL019 can cost hundreds of thousands of dollars. 

A number of grants have been given to the Ottawa Hospital, one group co-led by Anaesthesiologist and Assistant Professor for the Department of Anaesthesiology and Pain Medicine at the University of Ottawa and Associate Scientist Doctor Manoj M. Lalu. His team is working on studies which would lead directly into the BioCanRx trials.

Lalu explains their job is to cross all their T’s and dot all their I’s as they work towards a trial period for this treatment.

"The first trial would be a small trial, you want to make sure number one it’s what we call feasible or in other words doable. That’s very important especially for a complex intervention like this cell therapy, you need to deliver what you're suggesting you're going deliver."

As the group works through this pilot study, Lalu says they'll learn what works and doesn't work as they move towards a possible human trial.

Another member of the Ottawa Hospital, Haematologist Clinician Scientist Dr. Natasha Kekre, holds three grants: How to make CAR-T optimized for cancers, help facilitate the development of CAR-T in Canada and a pre-clinical project to create a therapy for cancers using viruses.


Image used with permission from Cancer Care Manitoba. CAR-T isn't just used to treat blood cancers, CAR-T cells are theoretically able to treat all cancers, with research in development currently to treat brain cancers.

Kekre says this treatment is designed for patients who are r/r, where their disease has returned after chemotherapy or never went away. These patients don't have many options with the most aggressive currently being a stem-cell transplant. Even with that therapy, the response rate for patients with the aggressive disease is as low as 30 percent.

The early CAR-T trials have seen response rates as high as 50 to 60 percent depending on the type of patient and disease.

The treatment is also extremely toxic says Kekre, as the treatment agitates the immune cells a patient who revives these cells can become incredibly sick, become confused, or end up in the intensive care unit in a coma.

Kekre describes some of these symptoms as the worst flu imaginable, however, these symptoms are reversible in almost all patients. Kekre explains this is one thing the team is looking to improve in terms of side-effects.

CAR-T therapy has received a lot of interest in its blood cancer treatment, however, Kekre says it goes beyond just blood cancers.

"Right now we are specifically targeting a protein or marker found in leukemia or lymphoma tumors. You can do the same model with CAR-T cells but attack other proteins on other cancers. There’s already a CAR-T cell being generated to see if maybe we can start using that in a clinical trial for brain cancers."

The team is hoping to begin patient trials with CAR-T therapy as early as January 2019.