uPAR-Directed CAR T Therapy Supported Tumor Elimination in Glioblastoma Models

A next-generation cancer therapy being developed at McMaster University has shown early promise as a treatment candidate for glioblastoma, the most aggressive and most common type of primary brain cancer in adults.  

In preclinical research, published today in Science Translational Medicine, scientists showed that the newly developed drug candidate can eliminate deadly glioblastoma tumours, which typically resist standard treatments and often recur rapidly, even after surgery, radiation, and chemotherapy. 

Researchers say the findings could mark an important advance against the disease, which has a median survival rate of less than 15 months from diagnosis.  

“New therapies for glioblastoma are urgently needed,” says Sheila Singh, a professor in McMaster’s Department of Surgery and principal investigator on the new study. “The standard of glioblastoma care has remained largely unchanged for over two decades, and the disease remains uniformly fatal because of it.”  

The new drug candidate, called a uPAR Chimeric CAR T cell, is an early-stage immunotherapy that was developed using antibodies created in partnership with scientists at Canada’s National Research Council in Ottawa.  

The novel cell therapy reprograms the body’s own immune system to recognize and attack a specific protein found on the surface of glioblastoma cells, called the urokinase receptor - or uPAR. This protein is also found on nearby support cells that fuel tumour growth, allowing the new therapy to not only eliminate deadly cancer cells, but also to dismantle the biological infrastructure that allows glioblastoma to persist and recur after treatment.  

Singh says that this work is part of a broader shift in cancer research, noting that scientists at the Memorial Sloan Kettering Cancer Center and Columbia University have also recently converged upon uPAR as a promising drug target in lung and pancreatic cancers. She says that this broader focus on uPAR is driving new collaborative efforts aimed at developing therapies that could potentially work across multiple hard-to-treat cancers. 

In the meantime, Singh, whose work is based out of McMaster’s Centre for Discovery in Cancer Research and is supported by NexusHealth, says that discussions about moving her lab’s recent discovery toward clinical trials are already underway. 

“This is a very exciting clinical candidate,” says Singh, who is also a professor of neuro-oncology and neurosurgery at King’s College London in the United Kingdom. “Our goal is to continue pushing this research forward, so that we can translate these preclinical results into first-in-human studies.” 

For William Maich, a postdoctoral fellow at McMaster and first author on the new study, the prospect of translating some of his own science into a tangible treatment that can improve quality of care is deeply motivating, especially in a field where meaningful clinical advances have been rare for decades. 

“It would be a dream come true for me to have some of my work help glioblastoma patients,” says Maich, who works in Singh’s lab. “Over the years, I’ve had the privilege of getting to know patients and their families through our bequeathal program at McMaster, and being able to finally present them with an alternative to the current standard of care would be a great honour.” 

Singh’s group has patented the new therapy and is now exploring potential commercial and clinical pathways for the drug.