Glioblastoma is the most common and aggressive brain tumor; a cancer against which most current treatment methods are largely ineffective.
The disease is deadly. As we’ve covered in recent stories, most patients with glioblastoma only live another 12-18 months following diagnosis. Roughly 25% of patients survive more than one year, and only 5% of patients survive more than five years.
But recently, glioblastoma has been the focus of a variety of studies and innovations – from a newly discovered brain pathway allowing promising treatment to kill glioblastoma cells, to an antidepressant capable of crossing the blood-brain barrier and aiding in the fight against the deadly disease.
Now, a team of Swiss researchers say that CAR T cells could be joining the list, as the key to targeting diseased cells, while sparing healthy cells.
Coming Up Short Against Glioblastoma
Effective treatments for glioblastoma have long eluded healthcare providers. Current treatment methods for the disease – such as surgery, radiation therapy and chemotherapy – often see tumors return.
In recent years, immunotherapies have had modest success among glioblastoma patients. But the approach is far from a treatment solution.
CAR T is the Key
A team from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) has successfully identified a specific marker on the surface of tumor cells, while also generating immune cells carrying an antibody to destroy the tumor cells.
The immune cells, known as chimeric antigen receptors T-cells (CAR T cells), are able to target diseased cells in the tumor that do not carry the antigen, while sparing the surrounding healthy cells.
CAR T cells have been getting a lot of attention lately, as the key player in a relatively new immunotherapy known as CAR T cell therapy.
Editor-in-chief at Breaking Cancer News, Jamie Reno, has covered CAR T extensively. It’s a treatment he knows a thing or two about, because it saved his life.
Jamie describes CAR T cell therapy as a living treatment that “deploys the patient’s own cells to fight cancer.”
According to researchers, these same CAR T cells that are the stars of their namesake therapy offer a key to fighting glioblastoma, as the cancer carries biological characteristics that make them particularly difficult to treat.
These unique characteristics give glioblastoma the ability to “induce a microenvironment that limits the attack of the immune system, they escape standard treatments and recur rapidly.”
”For several years we have been trying to identify the protein markers expressed by glioblastoma cells,” said Denis Migliorini, assistant professor in the Department of Medicine at the UNIGE Faculty of Medicine, ISREC Foundation Chair in Brain Tumour Immunology, member of the Translational Research Centre in Onco-Haematology (CRTOH) and attending physician in charge of the HUG Neuro-oncology Unit. ”One of these markers, PTPRZ1, proved particularly important: we were able to generate CAR T cells carrying antibodies targeting PTPRZ1. This is a first step towards CAR T cells effective against malignant gliomas.”
Effectively Targeting Tumor Cells
The research team first tested the CAR T cells in culture on both healthy cells and tumor cells to ensure they would limit their attack to the latter.
”To our surprise, not only did CAR Ts not attack healthy cells, but they were also capable, by bystander effect, of identifying and fighting tumor cells not expressing the PTPRZ1 marker,” said Migliorini. ”In this context, CAR Ts are probably capable of secreting pro-inflammatory molecules that are responsible for eliminating tumor cells even in the absence of the original marker when co-cultured with target positive tumor cells.”
Next, researchers tested the treatment in mouse models of human glioblastoma. These tests showed controlled tumor growth, “prolonging the lives of the mice remarkably well without signs of toxicity.”
The team says that these results, published in Cancer Immunology Research, represent a first step toward testing the approach in clinical trials with human Glioblastoma patients.
