In patients with the frequently fatal, rapidly progressive opportunistic brain infection progressive multifocal leukoencephalopathy (PML) for whom reversal of their immunodeficiency—the only treatment for PML—is impossible or would be too slow, there are currently no treatment options. While adoptive cellular immunotherapy—a strategy in which donor T cells are grown in culture with viral antigens to produce virus-specific T cells that are then given to patients—is increasingly being used successfully to treat various viral infections in post-transplant patients, whether this strategy offers a potentially powerful means to treat PML remains unclear, explains Erin Beck, MD, PhD.

For a study presented at the American Academy of Neurology’s 2019 annual meeting, Dr. Beck and colleagues sought to determine the safety and feasibility of treatment of PML with adoptive T cell therapy using T cells derived from patients’ first-degree relatives. “Our secondary outcomes were designed to measure efficacy and included survival as well as clinical, radiological, and immunological measures,” says Dr. Beck. “We focused on patients who did not have a readily reversible cause of immunosuppression and who were neurologically worsening at the time of enrollment.” Patients were treated with up to three infusions of polyoma-virus specific T cells (PyVST) each, with at least 28 days between infusions and followed with serial clinical exams, MRIs, and lumbar punctures for at least 1 year following their last infusion.

“We found that treatment with PyVST cells was safe, with no instances of immune reconstitution inflammatory syndrome (IRIS) that required treatment,” explains Dr. Beck. “Our strategy of using related donors was also feasible. Seven out of the 12 patients we treated survived PML, which was encouraging given that they were worsening at enrollment and not expected to do well without treatment.” Lower cerebrospinal fluid JC viral load in patients, JC virus seropositivity in donors, and anti-viral activity in the cell product were associated with survival.

Dr. Beck notes that while the study provides “a great deal about which patients may benefit most from this type of treatment and how to further optimize PyVST cell production and anti-viral activity in order to improve treatment efficacy, the number of patients treated was small and our results will need to be validated with further studies before being incorporated into general practice.”