Third-Party Donor Virus-Specific T Cells Are Efficacious in the Treatment of Refractory Viral Infection Following Allogeneic HSCT, but May Not Persist Post-Infusion

• Published in: Blood 2015-12, Vol.126 (23), p.623-623
• Main Authors: Withers, Barbara, Blyth, Emily, Clancy, Leighton, Burgess, Jane, Simms, Renee, Micklethwaite, Kenneth, Gottlieb, David
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.623.623

▪ The efficacy of adoptive transfer of stem cell donor-derived virus-specific T cells (VST) to prevent or treat viral infection in allogeneic HSCT is well established. However, this approach has some limitations. It is prerequisite on the donor cells being accessible, and virus seropositive. The generation of a product applicable to a single intended recipient is cost- and labour-intensive, and may not be immediately available in urgent clinical scenarios. Creation of a bank of cryopreserved third party donor-derived VST addresses these limitations. We established such a bank of 177 VST, specific for cytomegalovirus (CMV n=77), Epstein Barr virus (EBV n=55), and adenovirus (AdV n = 47). To date, 19 allogeneic HSCT patients have been treated with partially HLA-matched VST for viral reactivation or disease (CMV=17 (2 with CMV colitis), EBV=1, AdV=1); persistent despite at least 14 days of antiviral treatment. Patients were transplanted from unrelated (n=12), sibling (n=4), or haploidentical (n=3) donors. The graft source was PBSC (n= 15), cord (n=1), or bone marrow (n=3), and 12/19 patients underwent in vivo T cell depletion. The 17 patients treated for CMV received a median of 31 (15-113) days of antiviral therapy prior to infusion, and 14/17 were transplanted from a CMV negative donor. Patients were eligible for up to 4 infusions of 2x107/m2 VST if viral persistence was documented 2 weeks after initial infusion. VST were matched at a minimum of one HLA allele between VST and recipient, and chosen on the basis of greatest number of HLA matches with preference for products with viral activity restricted through a shared HLA. A total of 31 VST have been infused; 1 patient received 4 infusions, 1 patient received 3 infusions, 7 patients received 2 infusions, and 10 patients received 1 infusion. VST were matched at 1/6 (n=4) to 4/6 HLA alleles, with 24/31 infusions matched at both a class I and class II HLA allele. The antiviral activity of VST products (determined by MHC tetramer staining or cytokine response to epitope stimulation) generated from 12 third-party donors was predominantly restricted through class I HLA alleles: A1 (n=4), A2 (n=2), A2 + B7 (n=1), A2 + DRB04:01 (n=1), A2 + B35 + DRB01:01 (n=1), A24 (EBV-specific, n=1), B7 (n=1), and DRB01:01 (Adv-specific, n=1). Best viral response post-initial VST was assessed in 18 evaluable patients. A complete response (CR) was documented if virus PCR negativity was achieved at any time, and partial response (