Work

685. Restoration of Antiviral Immunity Following Hematopoietic Stem Cell Transplantation with Virus-Specific T-Lymphocyte Therapy

Year: 2016

Type: article

Abstract: Background: Adoptive immunotherapy using virus-specific cytotoxic T-lymphocyte (VST) products has been successful in restoring antiviral immunity after hematopoietic stem cell transplantation (HSCT). VST may be produced from a stem cell donor in 10-14 days using current rapid protocols, or banked, partially-HLA matched VST may be used as an “off the shelf” treatment. Objective: To evaluate the clinical efficacy of HSCT donor-derived VST and third-party VST for prevention or treatment of CMV, EBV, and adenovirus following HSCT. Design/Methods: VST were cultured from HSCT or third-party donors using a GMP-compliant rapid-manufacture protocol. VST were tested for specificity and non-alloreactivity via IFN-γ ELISpot and cytotoxicity assays. Patients were monitored for 45 days following infusion for toxicity and for up to 22 months for immune reconstitution. Results: Nineteen patients received VST on existing protocols, of which 15 products were derived from HSCT donors, and 6 were from partially matched, third-party donors. Sixteen patients were treated for CMV (N=11), EBV (N=5), and/or adenovirus infections(n=3), of which fourteen (88%) had partial or complete antiviral responses. Immune reconstitution against targeted viruses was seen using IFN-g ELISpot at a median time of 28 days following infusion. Three patients developed grade I-II GVHD within 45 days of VST infusion, all of which was treatment responsive. Sixteen of the 19 patients remain alive and free of active viral infection up to 22 months post-VST infusion. Conclusions: VST are effective for the restoration of antiviral following HSCT. Expansion of targeted viruses may further extend the utility of this therapy.

Source: Molecular Therapy

DOI: 10.1016/s1525-0016(16)33493-1