Fighting brain tumors with genetically modified immune cells
Published: Thursday, Sep 26th 2024, 12:40
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Scientists in Geneva have developed genetically modified immune cells that can target certain brain tumors such as glioblastoma. This should be possible while sparing healthy brain tissue. Clinical trials on humans are to follow.
Glioblastomas are the most malignant form of tissue degeneration in the brain. They have characteristics that make them particularly difficult to treat, as they are able to create a microenvironment that restricts the immune system's attack. They evade standard treatments and recur quickly, according to a press release issued by the University and University Hospital of Geneva (Unige/HUG) on Thursday.
Denis Migliorini, Assistant Professor at Unige and holder of the ISREC Endowed Chair of Immunology of Brain Tumors, is a specialist in "CAR-T" cells, or T lymphocytes with chimeric antigen receptors.
In this immunotherapy, T lymphocytes, i.e. immune cells, are taken from the sick person and genetically modified in the laboratory. They are equipped with antibodies that can recognize specific elements in tumour cells. They are then re-injected so that they can specifically attack the tumor.
"We have been trying for several years to identify protein markers that are expressed by the cells that make up these malignant gliomas," Migliorini is quoted as saying in the press release. "One of these markers, PTPRZ1, proved to be particularly important: we were able to generate CAR-T cells that carried antibodies against PTPRZ1," the expert added.
The scientists introduced the messenger RNA of the desired antibody into the T lymphocytes. The cellular machinery then ensures that the correct protein is produced to create the receptor, which is placed on the surface of the lymphocyte and recognizes the tumour target.
Effectiveness and safety
In order to verify that CAR-T only attacks tumor cells, the Geneva team first tested it in vitro on healthy and diseased cells.
They were pleasantly surprised that the CAR-Ts not only attacked healthy cells, but were also able to identify and combat diseased cells that did not carry the PTPRZ1 marker due to the "proximity effect", says Migliorini.
The second step was to test the treatment in a mouse model. Tumor growth was controlled and the life of the mice was remarkably prolonged without any signs of toxicity, as the paper published in the journal "Cancer Immunology Research" shows. The scientists conclude that all the signals are green for considering a first clinical trial in humans.
According to the University Hospital of Zurich, three out of every 100,000 people in Switzerland are diagnosed with glioblastoma every year. Men are affected more frequently than women.
©Keystone/SDA
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