Women with red glasses
Charlotte Grad was one of the first in Canada to receive CAR-T cell therapy when it was in trial stages. Now she is living cancer-free. (Photo: UHN)

A new cellular therapy program at the Princess Margaret Cancer Centre (PM) marks a new era in realizing the full potential of immunotherapy treatments for cancer patients. 

Chimeric Antigen Receptor or CAR T-cell therapy — one of the most promising life-saving immunotherapies on the horizon — will be offered as standard of care. 

CAR T-cell therapy is when the body's own immune cells are removed from a patient and genetically engineered to recognize and fight their own tumour. 

"It's the definition of personalized medicine," says Sarah Coyle, Manager of Medical Oncology and Hematology, and Project Manager for the Cellular Therapy Program.

"You're manufacturing your own cells to recognize the cancer and then attack it."

Using a process called apheresis, T-cells (a critical cell in the immune system) are removed from the patient's blood and genetically engineered to express a protein called a Chimeric Antigen Receptor (CAR).  This CAR allows the T-cells to recognize and kill the patient's cancer cells.

Multiple labs across UHN are involved

Patients receive a strong chemotherapy to make room for the new cells, and the CAR T-cells are infused back into their body. 

Six beds are dedicated to the program and with no small amount of effort. The therapy is so unique that every person involved needs to have extremely specialized training. There are specific requirements in handling the cells as well as caring for patients who may develop unique symptoms related to the infusion of the T-cells.

Multiple labs across UHN, including the blood and flow lab will be heavily involved. The PM cell processing lab will play an integral role. Dedicated oncologists and nurses, who are typically the first to identify any adverse side effects, need to know what to expect.

The Mount Sinai Intensive Care Unit is involved in helping manage any serious side effects, and social work and educational teams help our patients navigate the requirements needed to move forward with the treatment.

"This is not just a drug but is rather a living drug," says Dr. Christine Chen, hematologist and Medical Director of the Cellular Therapy Program, "and therefore special accreditation is needed for cell handling and management of unique side effects that require a lot of care for patients after infusion.

"Hundreds of people are involved in caring for one person. Our partnerships need to be strong."

Difference between life and death for some patients

To prepare, more than 300 staff have received specialized education. Even with the herculean effort, everyone is dedicated to bringing the therapy to patients.

"There is a lot of change and new work," says Sarah. "But we're on the forefront of delivering this to patients, and that's something we can all rally around."

For patients such as Charlotte Grad, access to CAR-T cell therapy has been the difference between life and death.

In March 2017 at age 63, Charlotte was diagnosed with stage 4 non-Hodgkin's lymphoma and swiftly began chemotherapy treatment. Her positive can-do attitude towards the journey ahead was shaken when she received further bad news: two unique mutations were discovered. Her cancer was resisting chemotherapy.

 That fall, she was told she had six to 12 months to live.

"I had to cancel my life," says Charlotte. "Everything became urgent.

"My kids got married...no plans were made beyond a month at a time."

The decision was made to try a stem cell transplant. Her oncology care team prepared, but with the chemo and progressing cancer, she wasn't strong enough to proceed with the transplant.

"I was living in a cloud of terminal diagnosis and a fog of several chemo failures and refractory treatments," she says.

One of the first in Canada to receive the treatment

Despite bad news after bad news, her mindset remained strong with the help of her primary hematologist, Dr. John Kuruvilla.

"He was ever-hopeful," says Charlotte. "I was always encouraged by him."

That is when Dr. Kuruvilla presented one more option for Charlotte: CAR T-cell therapy.

With a supportive force behind her, Charlotte decided to proceed with the revolutionary therapy in the fall of 2018.

"Without such a fantastic team at Princess Margaret, and the support of every single one of my friends and family, especially my children and partner, I could not have proceeded," she says.

 She is one of the first in Canada to receive the treatment in its trial phase.

Now, just over a year after her treatment, Charlotte is in remission, with a new lease on life.

'Look forward to new life lessons'

"I have a future now," she says. "I'm back in the gym; I'm taking a drama course and even going to Portugal.

"I have been able to rekindle my thirst for adventure, create new goals and look forward to new life lessons."

With the opening of the cellular therapy program, more patients like Charlotte will have a chance to plan for the future while embracing a healthy present.

Andrew Winter, Clinical Coordinator for the Cellular Therapy Program, has seen decades of patients such as Charlotte and is excited for this next frontier. 

"Our patients have been let down once, then again by treatment," he says. "Now, we have something to offer them.  Something that has a better chance of being a cure."

The Princess Margaret is the third centre in Ontario to offer CAR T-cell therapy as a standard of care, joining The Hospital for Sick Children (SickKids) in Toronto and Hamilton's Juravinski Cancer Centre.

Currently, it is only used for acute leukemia and non-Hodgkin's lymphoma, but the potential for CAR T-cell could carry across a wide array of cancers and other diseases.

For Charlotte, it's simple: "This is a game-changer."

The heart of processing cells at the Princess Margaret

A small but mighty team at the Princess Margaret (PM) played an integral role in CAR-T cell therapy becoming a standard of care: the Cell Processing lab. The lab is at the heart of PM’s extensive stem cell transplant program, allowing cells to be safely removed, processed and infused while maintaining the highest quality of care. To be able to offer CAR-T cell therapy, a highly trained group of laboratory professionals in the Cell Processing Lab, called stem cell specialists, need to process the T-cells before they are transfused. The cells are minimally manipulated and then preserved with a special medium, which allows for safe transportation to the manufacturing site for genetic modification. The process takes about four hours of delicate work and the specialists are directly involved with handing off cells to the care team for a safe arrival.

Team photo in lab coats
(L to R) The Cell Processing Laboratory team (Front row) Tulsidai Ramdass, Rashied Kawsher Molla, Mily Alvarez, Agustina Boriano, Arpita Parikh. (Back row) Orlay Lopez, Rouzbeh Chegeni, Mark Camacho, Ed Brindle, Melissa Kissoon, Ronal Ramos deArmas, Muhammad Badawi. (Missing) Valerie Mckay. (Photo: UHN)

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