Dr. Franz Sempf chills as he talks about how his idea of targeting specific cancer cells developed.
“I never thought I’d get this close to patients. I never thought something I built or designed would be put into clinical trials,” said Dr. says Zemp, an assistant professor. “I think it’s every medical person’s dream to build or be a part of something that can someday help someone.”
Zemp designed a chimeric antigen receptor (CAR) T cell therapy to attack alveolar soft tissue sarcoma (ASPS) for Calgary’s Milan Heck. In 2015, Heck was a patient at Alberta Children’s Hospital. After undergoing initial removal of a sarcoma in her hip, she was approached to donate a cancer sample. Clark H. Smith Tumor and Tissue Bank at the University of Calgary.
“I was thinking, why not? We’re not going to do anything with large amounts of tumor tissue. It was hard to imagine any kind of research and development from just a few samples,” he said at the time. The old Heck recalls: “I thought it might freeze somewhere.”
This donation will be one of many as her cancer kept coming back. During each surgery, a portion of the removed tissue is sent to a biobank. Some of these samples were used by Drs. Donna Senger, PhD, and Jennifer Chan, MD, developed a mouse model of Milan cancer. Researchers say this was a crucial part of the process.
“In 2021, I received an email from Dr. Douglas Mahoney informing me that a project was being started using my samples that could have great clinical potential,” Heck says. “He told me that a postdoc in his lab had developed a new CAR-T cell immunotherapy for my cancer, and it was showing signs of working.”
Find immunotherapy targets
ASPS is a unique form of cancer that affects children and young adults that is caused by rearrangements in a single molecule. Chromosomes break and reform, essentially creating new genes not found in nature. Professor Zemp wondered whether these irregular chromosomes could cause changes within the cells, making them a potential target for CAR T-cell immunotherapy. He looked for proteins that were present in cancer cells but not in normal cells.
“T cells, one of our immune cells, are great at killing cancer cells if they can find them,” Zemp says. “This treatment works by genetically engineering a patient’s T cells to detect cancer-specific markers. We genetically engineered Milan’s T cells in the lab and transferred them to mice. I gave it to the model.”
Zemp hoped that T cells would do the same thing they do in nature. He remembers the first time he checked on mice to see if their modified immune systems were responding.
“We were shocked to see such an immediate reaction from the mice. it was unbelievable! It was a cool day, probably the best day of my career,” says Zemp. “It wouldn’t have been possible without her sample. And not just to test the drug we developed. And the markers we chose to target were even after other treatments, Milan’s We also needed to test the hypothesis that cancer manifests consistently over time. Everything moved forward from there.”
It moved quickly. Collaborations were formed at the local, state, and national levels. Local collaborators included scientists from the University of Calgary, biomanufacturing experts from Alberta Precision Labs, and clinicians from Tom Baker Cancer Center and Alberta Children’s Hospital.
“We needed to quickly understand whether this drug we had developed had real-world potential. It wasn’t easy. It was a lot of work. We needed the right team. It took time to build it the right way,” says Dr. Mahoney, associate professor at CSM and associate director of basic and translational research at the Ernie Charbonneau Cancer Institute.
Establishment of Liddell Cancer Immunotherapy Center
Researchers quickly realized that what they learned from Heck’s cancer could be applied to other ASPS patients and perhaps other cancers.
“That’s probably what I’m most proud of. The entire effort from idea to first patient experience took less than three years. That’s very unusual. It’s a huge commitment to the university and the province of Alberta to accomplish this. Because we had a lot of resources and a lot of support from the Health Service (AHS),” Mahoney added.
Scientists at the University of California, Calgary say this surprising timeline and discovery was made possible by philanthropy.
“This kind of research is not possible without philanthropy. It’s that simple,” Mahoney says. “Translating discoveries and inventions into clinical practice is expensive and resource-intensive.”
Thanks to a generous $25 million gift from the Liddell family, the immunotherapy program has a bright future. The creation of the Liddell Center for Cancer Immunotherapy includes projects at several locations, including the Arthur JE Children’s Comprehensive Cancer Center.
“We are very excited about the future of immunotherapy as a mainstay of cancer treatment. From cell-based therapies like the CAR T cells created for Milan, to the development of new treatments. We are very excited about the future of immunotherapy,” says Charbonneau Director Chan. From antibodies to immunomodulators to cancer vaccines, we are working to find new ways to harness the body’s immune system to treat cancer and ultimately improve outcomes. We innovate, collaborate and leverage new technologies with our partners every day. ”
The Liddell Center will enable expansion of our translational pipeline from laboratory discovery and invention to biomanufacturing and testing of clinical-grade cell and immunotherapy products. Mahoney said the inclusion of scientists and clinicians at Arthur Child increases the potential for collaboration and speeds up the translation of ideas into clinical trials.
“We are extremely grateful to the Liddell family for this transformative gift,” said Dr. Todd Anderson, Cumming Medical Director. “This research is central to CSM’s precision medicine focus on finding personalized treatments specific to patients. This is a very exciting time in cancer research.”
Dr. Mona Shafey is excited to be a part of this scientific endeavor, which has the potential for new treatment options for patients. She says immunotherapy has proven to be very effective in some patients with blood cancers, particularly patients with an aggressive form of non-Hodgkin’s lymphoma called diffuse large B-cell lymphoma. .
“It can be very dramatic. In some cases, you can see results within a week to two weeks after treatment,” says CSM, a hematologist and clinical associate professor at Foothills Medical Center. says Mr. Sheifei. “And in fact, some patients have been shown to have a complete response within a month of receiving CAR T therapy.”
Although the results are promising and offer hope for new treatment options for some cancer patients, we have only scratched the surface of the potential of immunotherapy, and to date CAR-T cell therapy has been unsuccessful. It is important to remember that the It is used to treat blood cancer patients who have not responded to other treatments in hopes of achieving remission.
She hopes the Riddell Center will become a place where new drugs are developed, including new CAR-T therapies for a wide variety of cancers for many patients like Heck. Patients like Heck never imagined that the tumor tissue she donated could lead to personalized treatments. Or when she needs it.
“I remember being diagnosed at age 14. Doctors said there was no standard treatment for this cancer and that it was best to try radiation therapy and surgery,” Heck said. Masu. “My dream is that one day the CAR T therapy developed in the Mahoney lab will become the standard of care. I can’t say enough about this team. They are truly amazing people. The work they do. It’s not just the research, it’s the compassion they show and the work they’ve done to develop something that actually has promise. I’m so grateful to them for who they are.”
Heck recently completed her Bachelor of Health Sciences degree at the University of Calgary and is currently a research assistant in immunology at CSM. She plans to earn her master’s degree and is considering a career in the field of scientific translation. She clearly knows that what’s happening in her lab has the potential to translate into the real world, and she wants to help others understand that.
