Glioblastoma is the most common and aggressive brain tumor, with patients surviving less than two years after diagnosis. Current treatments could be more effective.
Researchers from the University of Geneva and Geneva University Hospitals have discovered a specific marker on glioblastoma cells and created immune cells called CAR-T cells that can target and destroy these tumor cells.
CAR-T cells can also attack nearby diseased cells, leaving healthy ones unharmed. This discovery is a promising step toward future clinical trials with patients. Glioblastomas are challenging to treat because they create an environment that protects them from the immune system and quickly return after treatment.
Denis Migliorini is an assistant professor at the University of Geneva and an expert in CAR-T cell therapy, a type of immunotherapy. This treatment involves taking immune T cells from patients, altering them in the lab to recognize specific proteins on tumor cells, and injecting them back into the patient to attack the tumor.
Migliorini’s team has been working to find protein markers on glioblastoma cells, and they discovered one called PTPRZ1. They successfully created CAR-T cells that target this marker, which is essential to developing effective treatments for malignant gliomas.
Most CAR-T cells are made with viral vectors suitable for blood cancers but can harm the brain. The brain is fragile, and long-lasting CAR-T cells can cause problems. Researchers used messenger RNA (mRNA) to guide T-cells in making antibodies that target tumor cells. This method allows the therapy to adapt as the tumor changes.
In lab tests, these CAR-T cells only attacked tumor cells. Due to a “bystander effect,” they could even target some without the specific PTPRZ1 marker. This means they can help fight other tumor cells, too.
When tested on mice with human glioblastoma, the treatment controlled tumor growth and extended the mice’s lives without harmful effects. By injecting CAR-T cells directly into the tumor, fewer cells were used, and side effects were reduced. With these promising results, the researchers are preparing for human clinical trials.
Journal reference :
- Darel MartÃnez Bedoya, Eliana Marinari, et al., PTPRZ1-targeting RNA CAR T cells exert antigen-specific and bystander antitumor activity in glioblastoma. Cancer Immunology Research. DOI: 10.1158/2326-6066.CIR-23-1094.
