Journal Article

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

Sharplin, Kirsty, Wainstein, Brynn, Dohrmann, Sara, Pearson, Rebecca, Chambers, Daniel, Beagley, Leone, Moore, Andrew, Dowling, Mark, Hunt, Stewart, Solomon, Matthew, Wang, Shiqi Stacie, Whyte, Morag, Yeoh, Zhi Han, Bajel, Ashish, Rehan, Sweera, Voogt, Meggie, Isbel, Nicole, Marlton, Paula, Tunbridge, Matthew, Cummins, Katherine, Chee, Lynette, Crooks, Pauline, Deambrosis, David, Panikkar, Archana, Raju, Jyothy, Khot, Amit, Fraser, Chris, Hanna, Diane, Gardiner, Bradley, Matthews, Katherine K., John, George, Tey, Siok-Keen, Hughes, David, Neller, Michelle A., Best, Shannon, Ramachandran, Shanti, Smith, Corey, Conyers, Rachel, Holmes-Liew, Chien-Li, Cole, Theresa, Le Texier, Laetitia, Soosay-Raj, Trisha, McNaughton, Peter, Badoux, Xavier, Srihari, Sriganesh, Hamad, Nada, Ng, Michelle, Harrison, Simon J., Hopkins, Peter, Kliman, David, Koo, Ray Mun, Tan, Sarah, Toro, Claudia, Francis, Ross, Grigg, Andrew, Ma, Kris, Khanna, Rajiv, Ritchie, David, Singhal, Deepak, Inam, Shafqat, Campbell, Scott, Irish, Ashley, Subramonia Pillai, Elango, Roos, Izanne, Reddiex, Hilary, Ng, Wei Yang, Cooney, Julian, Shaw, Peter, Nelson, Adam, F

2024

Overview

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. Adoptive T-cell immunotherapy offers promise to patients who are resistant to standard anti-viral strategies. Here the authors describe clinical observations in patients with viral complications treated with adoptive immunotherapy over the last 15 years.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/106 / 13/107 / 13/31 / 631/250/1619/554 / 631/250/251 / 631/250/255/2514 / 692/308/409 / Adolescent / Adoptive immunotherapy / Adult / Aged / Antiviral agents / Antiviral drugs / Australia / BK Virus - immunology / Cell therapy / Compassionate Use Trials / Cytomegalovirus / Drug resistance / Epstein-Barr virus / Female / Hemorrhagic cystitis / Herpesvirus 4, Human - immunology / Humanities and Social Sciences / Humans / Immunocompromised Host / Immunocompromised hosts / Immunotherapy / Immunotherapy, Adoptive - adverse effects / Immunotherapy, Adoptive - methods / Lymphocytes / Lymphocytes T / Male / Middle Aged / multidisciplinary / New Zealand / Patients / Retrospective Studies / Risk groups / Science / Science (multidisciplinary) / T-Lymphocytes - immunology / T-Lymphocytes - transplantation / Viral Load / Virus Diseases - immunology / Virus Diseases - therapy / Viruses / Young Adult