Compassionate access to virus-specific T cells for adoptive immunotherapy over 15 years
Michelle A. Neller, George Ambalathingal, Nada Hamad, Joe Sasadeusz, Rebecca Pearson, Chien‐Li Holmes‐Liew, Deepak Singhal, Matthew Tunbridge, Wei Yang Ng, Kirsty Sharplin, Andrew S. Moore, David Deambrosis, Trisha Soosay Raj, Peter McNaughton, Morag Whyte, Chris Fraser, Andrew Grigg, David Kliman, Ashish Bajel, Katherine D. Cummins, Mark R. Dowling, Zhi Han Yeoh, Simon J. Harrison, Amit Khot, Sarah Tan, Izanne Roos, Ray Mun Koo, S. Döhrmann, David Ritchie, Brynn Wainstein, Karen McCleary, Adam Nelson, Bradley J. Gardiner, Shafqat Inam, Xavier C. Badoux, Kris Pui Kwan, Claudia Toro, Diane Hanna, David J. Hughes, Rachel Conyers, Theresa Cole, Stacie Shiqi Wang, Lynette Chee, Jacqueline Fleming, Ashley Irish, Duncan Purtill, Julian Cooney, Peter J. Shaw, Siok‐Keen Tey, Stewart Hunt, Elango Pillai, George John, Michelle Ng, Shanti Ramachandran, Peter Hopkins, Daniel C. Chambers, Scott B. Campbell, Ross S. Francis, Nicole Isbel, Paula Marlton, Hilary Reddiex, Katherine Matthews, Meggie Voogt, Archana Panikkar, Leone Beagley, Sweera Rehan, Shannon E. Best, Jyothy Raju, Laëtitia Le Texier, Pauline Crooks, Matthew D. Solomon, Lea Lekieffre, Sriganesh Srihari, Corey Smith, Rajiv Khanna
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.