Phase I clinical trial of autologous Epstein–Barr virus-specific T cell therapy as treatment of progressive multiple sclerosis

Participants who meet the trial eligibility criteria following screening and review of blood test results will donate a 200-400 mL blood sample. Peripheral blood mononuclear cells from this sample will be used for laboratory generation of autologous latent membrane protein(LMP1&2)/Epstein-Barr virus nuclear antigen 1 (EBNA1)-specific T cells suspended in clinical grade normal saline. The investigational product is produced by stimulation with gamma-irradiated autologous peripheral blood mononuclear cells infected with the recombinant adenoviral vector AdE1-LMPpoly. This vector encodes multiple CD8+ T cell epitopes from the EBV latent proteins EBNA1 and LMP1&2. The T cell cultures will be assessed for cell yield, viability and T cell frequency. Approximately 5 weeks will usually pass between collection of the 200-400 mL blood sample and first cell administration. Patients will receive the T cell therapy intravenously, at fortnightly intervals. Each dose is given once, the initial dose will be 5 × 10^6 T cells, followed by doses of 1 × 10^7, 1.5 × 10^7, and 2 × 10^7 cells. A total of 4 doses will be given over a period of 8 weeks. The cells will be administered via an intravenous line drip, allowing the slow administration of T cells into the blood, rather than a bolus of cells. The cells will be thawed into 20 mL saline, and will be administered to patients via a normal saline intravenous line over 10–15 min. Participants will be followed up for 27 weeks from the first cell administration.