Researchers at Hannover Medical School (MHH) have identified biomarkers that can predict which patients with progressive multifocal leukoencephalopathy (PML) will benefit from therapy with immune checkpoint inhibitors (ICI). The results were published in the journal JAMA Neurology.

PML is a rare but usually fatal brain infection caused by human polyomavirus 2 (JC virus). It occurs mainly in severely weakened immune systems and destroys the brain tissue within a few weeks. One treatment option is the administration of checkpoint inhibitors, which reactivate the immune system. However, success varies widely, and serious side effects are possible. Until now, there have been no reliable predictions as to who will benefit from the therapy.

The interdisciplinary team led by Prof. Dr. Thomas Skripuletz (Department of Neurology with Clinical Neurophysiology) evaluated data from 111 PML patients from 39 clinics worldwide who were treated with ICI between 2021 and 2024. In some of the patients, the presence of functional, JC virus-specific T cells was tested in the blood before the start of therapy.

The evaluation revealed clear differences:

• Patients with detectable virus-specific T cells showed significantly higher response rates, better functional courses, lower viral loads in the cerebrospinal fluid and a significantly higher probability of survival during and after ICI treatment.
• At the same time, they experienced fewer immune-mediated side effects.

In patients without these T cells, ICI therapy was usually less effective. The MHH offers an alternative here: In the alloCELL registry, virus-specific T cells are collected from healthy donors and isolated precisely. These allogeneic DIAVIS T cells can be infused in the absence of their own immunity. Thanks to the registry and the high production capacity, suitable preparations are available within a few days – even for centers abroad.

The study shows for the first time in a larger cohort that a simple blood test for JC virus-specific T cells can serve as a biomarker. It identifies patients for whom checkpoint inhibitors are particularly likely to be effective and better tolerated. The results confirm the crucial role of existing antiviral immunity and make the test a potential standard before ICI therapy is initiated. The aim is to quickly transfer the findings into clinical practice and to make the treatment of PML more targeted and safer.

Original paper:

Virus-Specific T Cells and Response to Checkpoint Inhibitors in Progressive Multifocal Leukoencephalopathy | Neurology | JAMA Neurology | JAMA Network

Editor: X-Press Journalistenbüro GbR

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