Rapid success: innovative therapy stops deadly brain inflammation PML

MHH team successfully uses foreign immune cells against the human JC virus to cure seriously ill patients.

Progressive multifocal leukoencephalopathy (PML) is a rare but serious brain infection. It gradually destroys brain tissue and often leads to death within a few weeks. It is caused by the human polyomavirus 2 – also known as the John Cunningham (JC) virus. In 2021, an interdisciplinary team at the Hannover Medical School (MHH) led by Professor Dr Thomas Skripuletz, senior physician at the Clinic for Neurology with Clinical Neurophysiology, found a groundbreaking way to stop the virus from spreading. Since then, the clinic has been offering a treatment with new immune cells that can suppress the virus in the body of those affected. These directly isolated allogeneic virus-specific DIAVIS T cells come from the blood of healthy people who were infected with the virus. They have precisely fitting defence cells from the group of white blood cells. The T-lymphocytes recognise the attacking JC viruses as foreign to the body and initiate an immune response.

The DIAVIS-T cells are isolated directly from donor blood at the Institute for Transfusion Medicine and Transplant Engineering and are available for therapy within 24 hours. In a scientific evaluation of 28 patients, the researchers have now analysed the effectiveness of their therapy. ‘We found that the majority of our patients respond to the treatment, recover from their symptoms and survive the virus infection thanks to the therapy,’ emphasises Professor Skripuletz. The results have been published in the journal JAMA Neurology.

Dormant virus is reactivated

The virus infects around 70 to 90 per cent of people worldwide, without most of them even noticing. But once it enters the body, the genetic material of the pathogen remains dormant there. If the immune system is weakened or shut down by a serious illness or immunosuppressive medication, the virus can undergo a genetic mutation. This mutation enables the virus to migrate via the blood into the central nervous system and infect cells there. Until the development of the new treatment method, there was only one option for patients taking drugs to suppress their immune system: the immunosuppressants were discontinued. Since the discovery of the therapeutic option with DIAVIS T cells, PML patients from Germany and abroad have been coming to the MHH for treatment. However, so far it has been a case-by-case decision for this treatment option.

Unique T-cell donor registry

However, the transfer of DIAVIS T cells only works if the tissue markers of the donor cells match those of the recipient by at least 50 per cent, i.e. they are HLA partially matched. The virus-specific T cells usually come from family donors or from the unique T cell donor register alloCELL at the MHH. ‘There, we not only register the HLA characteristics of the blood cells, but also determine the number of specific T cells against different viruses at the same time,’ says Professor Dr. Britta Eiz-Vesper, an immunologist at the MHH Institute for Transfusion Medicine and Transplant Engineering. Because the institute is also one of Germany’s leading manufacturers of virus-specific T cells, the scientist can quickly find suitable individuals for a T cell donation and then provide the T cell products within a few days of the patient’s request. This short time frame is crucial for people with PML. Because only a low dose of cells is required, the likelihood of complications such as graft-versus-host disease, in which the donor’s immune cells attack the recipient’s body, is low because only a low dose of cells is required.

Method can also be applied to other viral diseases

In order to scientifically confirm the results, the researchers are now preparing a phase 2 clinical trial, which is funded by the German Federal Ministry of Education and Research (BMBF). If the clinical trial provides general proof of the effectiveness of the treatment method, it could become an approved therapy for all PML sufferers. And this may affect more people than previously assumed. ‘PML is probably not often enough on the radar of treating physicians, also because there has been no cure for it so far,’ says the neurologist. And in the long term, the therapeutic principle could also be extended to other neurological viral diseases. ’We are convinced that our method will revolutionise the treatment of infectious diseases.’

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For further information, please contact Professor Dr Thomas Skripuletz, skripuletz.thomas@mh-hannover.de, phone +49 511 532-3816.

Originalpublikation:

The original paper ‘Directly Isolated Allogeneic Virus-Specific T Cells in Progressive Multifocal Leukoencephalopathy’ can be found here: https://jamanetwork.com/journals/jamaneurology/fullarticle/2824325

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