A team of researchers in Geneva has disclosed a breakthrough that could provide new hope to patients suffering from one of the deadliest forms of brain cancer. Scientists at prominent Swiss institutions have created personalised immune cells capable of identifying and combating glioblastoma, an aggressive malignancy with a five-year survival rate of fewer than five per cent. 

Glioblastoma is notorious for its rapid spread and resistance to nearly all available treatments, including radiation, chemotherapy, and even contemporary immunotherapy. The tumour differs from many other malignancies in that it hides from the immune system. "However, glioblastoma is unique in that it contains very few T cells, which are immune cells that can recognise and destroy cancer cells," noted Valerie Dutoit, a study researcher. "This is why glioblastoma… does not respond to standard immunotherapies."

To overcome this issue, the researchers developed CAR-T cells, which are special immune cells. These are T cells extracted from the patient's own blood and genetically engineered in the lab to aid in the identification of cancer cells. Once enhanced, the cells are returned to the patient to locate and eliminate the tumour. 

The researchers made a significant step forward when they discovered two key targets associated with the cancer. "In a previous study, we identified an important target, the PTPRZ1 marker, which is present on the surface of certain tumour cells," said Denis Migliorini, who leads the neuro-oncology team involved in the research. However, focusing on a single target was deemed too dangerous because glioblastoma contains a variety of cell types, making relapse likely. 

To address this, the researchers introduced a second target: tenascin-C, a protein found in the jelly-like environment that surrounds the tumour. When CAR-T cells assault this protein, they cause severe inflammatory responses that kill adjacent cancer cells. "Furthermore, we have been able to demonstrate that CAR-T cells are capable of locally destroying cancer cells that do not produce tenascin-C," according to Migliorini. 

Another challenge faced by the researchers was the rapid fatigue of CAR-T cells once they entered the tumour. "By identifying three markers of cell exhaustion and counteracting their activity, we were able to significantly prolong the efficacy of CAR-T cells," Dutoit told me. 

The excellent findings in animal models have set the stage for a clinical trial to commence next year. "Our goal is to generate genetically modified immune cells against several targets at once in the hope of reaching as many cancer cells as possible," according to Migliorini. For patients with few options, this customised approach could be a significant step towards more effective treatment.