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Establishment of a bank of blood donor derived epstein barr virus specific T cell lines for treatment of post-transplant lymphoproliferative disease

      EBV driven lymphomas associated with immunosuppression are a significant problem, particularly after transplantation. Conventional treatment [withdrawal of immunosuppression, administration of rituximab / chemotherapy] is often effective but risks organ rejection and causes significant side effects. EBV specific CTLs generated in vitro from autologous lymphocytes can be effective with few side effects, but take several months to prepare and so are difficult to deploy in clinical practice. We have established a bank of EBV CTLs derived from blood donors for issuing ‘off the shelf' to partially HLA matched patients. A panel of New Zealand blood donors was chosen to maximise the probability of HLA class I and II matches. We estimate that a panel of 25 donors should provide a match for around 80% of patients. So far 25 LCLs have been made, 16 CTLs generated of which 7 are approved for clinical release. Since the Centre was granted an MHRA ‘Specials’ licence for manufacture of Advanced Therapy Medicinal Products in January 2012, there have been enquiries about 18 patients: 7 improved on conventional treatment, 5 died before cells could be issued and 6 have received EBV CTL. The clinical indications have been 3 cases of post transplant lymphoproliferative disease, 2 with congenital immunodeficiency as a bridge to allogeneic HSC transplantation and 1 case of EBV driven leiomyosarcoma post-cardiac transplant. Clinical improvement has been seen in 3/4 assessable patients. An allogeneic EBV CTL bank can be operated for international use under curent regulatory legislation and is a valuable addition to current therapies for selected patients.
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