From the MHH

Treating severe EBV infections with individual immunotherapy

Immune cells from outside the body can support the weakened immune system of seriously ill people. A multicentre study led by the MHH has now also demonstrated this for severe Epstein-Barr virus (EBV) infections.

Professor Dr Maecker-Kolhoff (left) and Professor Dr Britta Eiz-Vesper sit in the Institute for Transfusion Medicine and hold a patient file in their hands. Copyright: Karin Kaiser / MHH

Enabling individual immunotherapies with customised T cells: Professor Dr Britta Maecker-Kolhoff (left) and Professor Dr Britta Eiz-Vesper. Copyright: Karin Kaiser / MHH

When conventional treatment options fail in diseases such as severe viral infections or associated cancers, so-called adoptive immunotherapy comes into play. In this procedure, living immune cells are isolated from healthy individuals, multiplied if necessary, treated if required and then transplanted. T-cells in particular are promising candidates, as they can recognise the disease-causing antigens precisely and kill their target cells. In this way, specific cellular immunity should be transferred to the patients. In a multicentre case series, a team from Hannover Medical School (MHH) led by Professor Dr. Britta Eiz-Vesper from the Institute of Transfusion Medicine and Transplant Engineering and Professor Dr. Britta Maecker-Kolhoff from the Department of Paediatric Haematology and Oncology has now shown that the method can also help with severe infections with the Epstein-Barr virus (EBV).

The virus can cause infectious mononucleosis (mononucleosis) and is linked to the development of cancer. The researchers produced EBV-specific, personalised T cells to strengthen the defences of immunocompromised people against the virus. The T cells, which are precisely tailored to the patients, come from stem cell donations, unrelated donations and unrelated donations from the globally unique T cell donor register alloCELL at the MHH. This has existed since 2013 and now has more than 4,000 potential donors. The 500th T-cell product has just been produced, a personalised therapeutic for a person with adenovirus infection after stem cell transplantation. In the multicentre study, the researchers produced EBV-specific T-cells for 37 patients, some of whom were severely ill after transplantation or because of recurrent EBV infection. "About 75 to 80 per cent of those affected responded to the treatment," says Professor Maecker-Kolhoff. "Overall, the cell therapy was very well tolerated." The results of the study have been published in The Journal of Clinical Investigation.

Tailor-made immunotherapy for immunocompromised patients

"Thanks to our experience, we are able to produce the T cells within a few days," says Professor Eiz-Vesper. This is possible so quickly because the alloCELL register not only stores the HLA tissue characteristics of the blood cells, but also the number of specific memory T cells against the different viruses. "This allows us to use effective and compatible T cells from donors very quickly for cell therapy, even if they are not related to the potential recipients." The transfer of EBV-specific T cells was able to restore the immune-compromised sufferers' defence capabilities. "The patients have benefited considerably from the customised immunotherapy," notes Professor Maecker-Kolhoff. "The success of the treatment can be seen in both the drop in viral load and the decrease in symptoms associated with EBV infection."

Fast to produce, clinically effective and well tolerated is the bottom line of immunotherapy. "Our data suggest that the transfer of EBV-specific T cells is a promising therapeutic approach to successfully treat immunocompromised people with life-threatening EBV infection," says the paediatric haematologist.

Text: Kirsten Pötzke