Compassionate access to virus-specific T cells for adoptive immunotherapy over 15 years

<title>Abstract</title> Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral strategies. We present a retrospective analysis of 75 patients from 15 hospitals across Australia and New Zealand, treated over the last 15 years with “off-the-shelf” allogeneic T-cells directed to a combination of Epstein–Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), John Cunningham virus (JCV) and/or adenovirus (AdV) under the Australian Therapeutic Goods Administration’s Special Access Scheme. Most patients had severe post-transplant viral complications, including drug-resistant end-organ CMV disease, BKV-associated haemorrhagic cystitis and EBV-driven post-transplant lymphoproliferative disorder. Adoptive immunotherapy was well tolerated with few adverse effects. Importantly, 50/75 (66.7%) patients showed definitive clinical improvement including reduction in viral load, clinical symptoms, complete resolution of end-organ disease and remained disease free. Based on this long-term encouraging clinical experience, we propose that a dedicated nationally funded centre for anti-viral cellular therapies should be established to provide T cell therapies for critically ill patients for compassionate use.