GCAR1 Cell Therapy Shows Promise in Solid Tumor Patients

University of Calgary and McMaster University researchers discovered a unique target present on a specific group of solid cancerous tumours. 

Armed with that information, UCalgary scientists developed a new experimental therapy based on Chimeric Antigen Receptor T cell therapy (CAR T) that harnesses a patient’s immune system, training it to find the target and destroy the cancerous cells. 

Published in Nature and Nature Cancer, the findings provide a blueprint for combating some treatment-resistant cancers.  

“We developed a first-in-class CAR T cell therapy called GCAR1 that shows strong preclinical and early clinical promise in sarcoma, and other cancers,” says 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. “Our colleagues at McMaster have validated the therapy in mouse models of a deadly brain cancer. This research reflects a close collaboration between the University of Calgary, Cancer Care Alberta and key partners around the country, allowing discovery science and clinical expertise to work hand in hand.” 

The work is a testament to the support of Calgary’s philanthropic community and the power of collaboration, Mahoney adds. 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. How philanthropy powered a UCalgary cancer immunotherapy breakthrough

Promising single-patient clinical trials

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 dive deeper into 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. 

Calgary man thankful for research 

With insights from that data, a second patient 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.

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“This clinical trial gave me hope. I was told there wasn’t anything more that could be done to treat my cancer,” says 55-year-old Kent B., husband and father of two daughters. “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 had shrunk and some had disappeared.”

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 in size. 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.”

An idea in the lab results in a new therapy for treatment resistant cancer 

First author of the study, Dr. Franz Zemp, PhD, 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 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 cancers and glioblastomas. The Nature paper led by McMaster researchers delves into the pre-clinical findings associated with glioblastomas. 

Research in the Mahoney lab 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 (living organisms found in and on your body, such as in your gut and on your skin), to detect, respond to and repair disease at its source.