EPO2229 – Preliminary phase 1 safety of ATA188, a pre-manufactured, unrelated donor (off-the-shelf, allogeneic) Epstein-Barr virus (EBV)-targeted T-cell immunotherapy for patients with progressive multiple sclerosis (MS)
Background and aims
Epidemiological and serological evidence suggest EBV infection is associated with MS pathogenesis. Previously, we showed that treatment with an autologous EBV-targeted T-cell immunotherapy in 10 patients with progressive MS may prevent MS progression and improve clinical symptoms. This study evaluates safety and feasibility of monotherapy with pre-manufactured, unrelated donor (off-the-shelf, allogeneic) EBV-targeted T cells (ATA188) for adults with progressive MS.Methods
A phase 1 multicentre, open-label, single-arm, 2-population, dose-escalation study enrolled EBV-seropositive adults with primary/secondary progressive MS (NCT03283826). Cohorts 1-4 receive 5.0×106, 1.0×107, 2.0×107, and 4.0×107 cells, respectively, on days 1, 8, and 15 in 2 cycles. Plasma inflammatory biomarkers (IL-2, IL-1β, TNF-α, IL-6) are monitored throughout treatment.Results
By 7 January 2019, 6 participants in cohort 1 (mean age: 58.2 years; 50% female) and 6 participants in cohort 2 (mean age: 56.7 years; 83% female) have received ≥1 dose. No dose-limiting toxicities or serious or grade ≥3 treatment-emergent adverse events (TEAEs) were reported. TEAEs occurred in 58% (7/12) participants (4/6 in cohort 1 and 3/6 in cohort 2); all TEAEs were grade 1 (17%) or grade 2 (42%). Most common TEAEs (n=2) were rhinorrhoea, fall, contusion, and headache. Two participants reported possibly-related grade 2 TEAEs. In cohort 1, 3 participants experienced upper respiratory infection symptoms, with 2 developing symptoms 2-5 months after treatment. Inflammatory cytokines remained at or near baseline throughout treatment.
ConclusionInitial safety data indicate ATA188 is well tolerated by adults with progressive MS and support proceeding with the study and identification of recommended phase 2 dose.
In this vaccine they take CD8 T cells that are responsive to Epstein Barr Virus. They spot virally infected cells and kill them. This is not news they have done this already. There they took the individual cells made the antiviral cells and then injected them. Personalised medicine. However in this case they are made by some one else. These are termed allogeneic cells.
This makes it easier to make as a produce as one cell can be mass produced allowing for better quality control and more of a pharmaceutical product and so it may be one cell may be suitable for many different people.
This study says they are safe. Immunologically I do not really buy this approach. I am sure they an matched for important transplantation antigens so they will work, but the cells will be different and so rejectable but the immune system of the recipient. Next and more worrying is that the the cells may be able to reject the the person they are going into.
A theorectical poosibility that I hope doesn’t happen. But if it does it will be a case of I told you so.