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Possibly lifesaving therapy in refractory PML

Presented by
Dr Erin Beck, National Institute of Health in Bethesda, USA
AAN 2019
Transfer of anti-polyomavirus-specific T cells (PyVSTs) from healthy related donors is feasible and safe as adoptive immunotherapy of severely immunocompromised patients with refractory progressive multifocal leukoencephalopathy (PML). Encouraging results in 12 patients suggest PyVSTs may be a lifesaving therapy [1].

PML is an opportunistic infection of the central nervous system caused by activation of the JC polyomavirus (JCV) in immunosuppressed patients. “Until now, there has been no treatment for PML, which is almost like a death sentence for the patient”, explained Dr Erin Beck (National Institute of Health in Bethesda, USA). “Basically, what we did was borrow immune cells from close relatives of the patients and make them active against the JVC.” Dr Beck's group used peptide libraries derived from BK Large T (LT) and Viral Protein 1 (VP1) that are highly cross-reactive with the structurally homologous JC proteins. PyVSTs were then generated from first-degree relatives of patients with refractory PML. Patients received 1x106 PyVST cells/kg, which could be followed by one or two additional infusions at 2x106 PyVSTs/kg, at minimal intervals of 28 days. The study's primary endpoint was safety.

In 12 subjects who received at least one infusion, there were no serious treatment-related adverse events. Dr Beck was particularly relieved to see no cases of overt immune reconstitution inflammatory syndrome, which can be fatal in itself. There were also no infusion reactions or graft versus host disease. The therapy was feasible; 7 patients (58%) survived and showed signs of neurological improvement. Dr Beck: “We did not expect them to do so well, since their condition was deteriorating even around the time of the first infusion. So, the results are very encouraging.” She could not say who benefitted the most from this therapy and which markers might predict survival.

1. Cortese I, et al. AAN 2019, Plen01.002.

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