Progressive multifocal leukoencephalopathy (PML) is a life-threatening rapidly progressive demyelinating disease of the central nervous system. It is caused by infection with JC virus (JCV), which is favored by polyetiologic immunodeficiency syndromes. To date, there is no approved effective therapy. In 2018, an open case series described the successful treatment of three PML patients with allogeneic virus-specific T cells (Muftuoglu M, Olson A, Marin D, et al. Allogeneic BK Virus-Specific T Cells for Progressive Multifocal Leukoencephalopathy. N Engl J Med 2018;379:1443-1451.).
At the Department of Neurology at Hannover Medical School (MHH), Germany, two patients with severe PML have now been successfully treated with BK virus-specific T cells for the first time, according to Prof. Günter Höglinger, MD, director of the department.
The treatment used BK virus-specific T cells that also target JCV because of a similarity between the JC and BK virus epitopes, according to Prof. Thomas Skripuletz, MD, one of the lead authors of the study (Hopfner et al., 2021). The BK virus-specific T cells administered were from partially HLA-matched donors. Stem cells were obtained from blood via leukapheresis. In contrast to the previously described cases from the USA, suitable donors for the patients treated at MHH were identified in a very short time by HLA typing from a pre-screened donor database of potentially available donors. “This time advantage seems particularly important because initiating therapy as soon as possible seems to be crucial for the extent of the expected therapeutic success,” Höglinger said.
Within a few weeks, both patients experienced an improvement in all neurological symptoms, accompanied by a significant decrease in viral load in the CSF and a regression of the image morphological changes in the MRI. In addition, the administration of the donor cells evoked a relevant number of endogenous BK- and JC virus-specific T cells in the patients, “as an activation of their own immune response,” said Franziska Hopfner, MD.
Therapy with allogeneic BK virus-specific T cells represents an innovative and promising therapeutic concept for the treatment of PML, a disease that has so far been infectious and resistant to therapy. This highly complex therapeutic procedure requires rapid action after diagnosis as well as an interdisciplinary medical setting with close cooperation of different disciplines, in particular neurology, neuroradiology, hematology, transfusion medicine, transplant engineering and virology. The preliminary results of this novel therapeutic concept raise great hope – controlled clinical trials must follow without fail, says Prof. Günter Höglinger.
In the meantime, further patients with PML have been successfully treated or are currently being treated at the Department of Neurology of the MHH. Inquiries regarding the treatment of PML patients as well as enrollment in the PML registry to document the natural history of the disease as a basis for conducting a controlled therapy study, can be directed to the following email address: Cure.PML@mh-hannover.de.
Franziska Hopfner*, Nora Möhn*, Britta Eiz-Vesper*, Britta Maecker-Kolhoff, Jens Gottlieb, Rainer Blasczyk, Nima Mahmoudi, Kaweh Pars, Ortwin Adams, Martin Stangel, Mike P. Wattjes*, Günter U. Höglinger*, Thomas Skripuletz*