Calgary, AB - Researchers with the Charbonneau Cancer Institute at the University of Calgary and McMaster University have identified a unique target present on a specific group of solid cancerous tumours. Using this discovery, UCalgary scientists developed an experimental chimeric antigen receptor (CAR) T‑cell therapy that trains a patient's immune system to recognize this target and kill the cancer cells. The work, reported in companion papers in Nature and Nature Cancer , offers a blueprint for tackling solid tumours that resist current treatments.
"We've developed a first-in-class CAR T cell therapy, called GCAR1, that is showing strong preclinical and early clinical promise in sarcoma and other cancers. Our colleagues at McMaster University have further demonstrated its potential in mouse models of a deadly brain cancer. This work reflects a close collaboration between the University of Calgary, Cancer Care Alberta, Alberta Precision Laboratories, and other key partners around the country, bringing discovery science and clinical expertise together at every step." - Dr. Douglas Mahoney, PhD, director of the Riddell Centre for Cancer Immunotherapy at the Cumming School of Medicine and the principal investigator on the Nature Cancer study.
Mahoney says the work is a testament to the support of Calgary's philanthropic community and the power of collaboration. Boreal Biomanufacturing, part of The Ottawa Hospital, played a key role in this advance by manufacturing the virus used to engineer the CAR T cells. BC Cancer also provided critical reagents required for the biomanufacturing.
In Calgary, the therapy has been given to two Canadian patients with alveolar soft-cell sarcoma, a rare type of malignant tumour. The first patient, Stéphanie Alain, lived significantly longer than expected. Her doctors say the therapy extended her life expectancy by 18-months. Her bravery, in the face of tremendous health challenges, and her willingness to be part of this important study throughout her treatments allowed the scientists to look more closely at how to make the medicine more effective. Co-principal investigator Dr. Sorana Morrissy, PhD, led the data science team.
"We anticipated learning something from Stéphanie's tissue and studied lung biopsies taken before and after treatment. We also generated data from dozens of blood samples, each comprising many thousands of cells," says Morrissy, associate director of Discovery and Innovation at the Riddell Centre.
With insights from that data, a second patient, a 55-year-old man from Calgary was treated with GCAR1 in combination with a well-tolerated effective companion immunotherapy. The results have been overwhelmingly positive. His progress is still being followed.
"This clinical trial gave me hope. I was told there wasn't anything more that could be done to treat my cancer. I saw several CT scans of my cancer. It had metastasized to my lungs. After the second therapy the scans showed that many of the tumours shrank, and some had disappeared." - Kent B., husband and father of two daughters.
Kent's treatment at the Arthur J.E. Child Comprehensive Cancer Centre was overseen by Dr. Mona Shafey, MD, a clinician and co-principal investigator on the study.
"One of the lesions in Kent's lungs was over 2.5 centimeters in size, and now it's less than one centimeter. There was another smaller lesion that we could see on the first scan and then barely see it on the second," says Shafey, a hematologist and cell therapy specialist at the Arthur Child. "With research we can bring new experimental treatments to patients who have exhausted all standard treatments. Cancer Care Alberta's leadership in conducting early-phase clinical trials and caring for patients receiving novel therapies is helping accelerate promising research into treatments that can extend and improve lives."
First author of the study, Dr. Franz Zemp, PhD'13, says CAR T therapy has changed cancer treatment, and he believes, while it's still early days, the Mahoney lab's discovery and development of a GCAR1 therapy could have a global impact on sarcomas and other cancers one day.
"We have had laser focus on this new target since 2021. Within six-months of building the medicine we had data back from mouse studies. The results were so striking we were able to get approval and move the therapy to a patient in 2023," says Zemp an adjunct assistant professor in the Department of Biochemistry and Molecular Biology. "That speed of translation from the lab to the clinic is remarkable."
The researchers are studying Kent's tumour samples before and after the GCAR1 therapy and are already working toward more advanced versions of the GCAR. The distinct marker the GCAR therapy targets is also present on kidney and brain cancers. The Nature paper led by Dr. Sheila Singh, MD, PhD, at McMaster, reports on the exciting pre-clinical success of GCAR1 against glioblastomas.
This research is one example of therapies being developed as part of the Living Medicine Initiative at the Cumming School of Medicine. These therapies use the body's own building blocks, including cells, genes and microbes to detect, respond to, and repair disease at its source.
The study conducted at UCalgary was supported by generous philanthropic contributions, as well as grants from Canadian Cancer Society, Canadian Institutes of Health Research (CIHR), BioCanRx, Alberta Children's Hospital Foundation and Alberta Cancer Foundation. Additional support is detailed in the paper.
Mahoney and Zemp are the inventors of the GCAR therapy and have a patent pending.
