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

Nat Commun. 2024 Dec 3;15(1):10339. doi: 10.1038/s41467-024-54595-2.

Abstract

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 78 patients from 19 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 is well tolerated with few adverse effects. Importantly, 46/71 (65%) patients show definitive clinical improvement including reduction in viral load, clinical symptoms and complete resolution of end-organ disease. In addition, seven high-risk patients remain 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 considered to provide T cell therapies for critically ill patients for compassionate use.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Australia
  • BK Virus / immunology
  • Compassionate Use Trials
  • Female
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunocompromised Host
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Male
  • Middle Aged
  • New Zealand
  • Retrospective Studies
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / transplantation
  • Viral Load
  • Virus Diseases / immunology
  • Virus Diseases / therapy
  • Young Adult