Addition of varicella zoster virus-specific T cells to cytomegalovirus, Epstein-Barr virus and adenovirus tri-specific T cells as adoptive immunotherapy in patients undergoing allogeneic hematopoietic stem cell transplantation

作者：Ma Chun K K; Blyth Emily; Clancy Leighton; Simms Renee; Burgess Jane; Brown Rebecca; Deo Shivashni; Micklethwaite Kenneth P; Gottlieb David J^*

来源：Cytotherapy, 2015, 17(10): 1406-1420.

DOI：10.1016/j.jcyt.2015.07.005

• adoptive immunotherapy
• haematopoietic stem cell transplant
• immune reconstitution
• T cell therapy
• varicella zoster-specific T cells

Background aims. Virus-specific T-cell immunotherapy is emerging as a promising management strategy for virus infections in patients after hematopoietic stem cell transplant (HSCT). Here we present outcomes of 10 adult patients who received multi-virus-specific T cells prophylactically after HSCT. Methods. Donor-derived cytomegalovirus (CMV)-, Epstein-Barr virus (EBV)-, adenoviral- and varicella zoster virus (VZV)-specific T cells were generated in a single culture and administered to HSCT patients at a dose of 2 x 10(7)/m(2) virus-specific T cells at a median of 63 days post-transplant. Patients were monitored for 12 months for evidence of viral reactivation and graft-versus-host disease. Results. There was no acute infusion-related toxicity. Six patients developed CMV reactivation after T-cell infusion with a median peak CMV DNA titer of 600 copies per milliliter, and 1 received CMV-specific pharmacotherapy post-infusion. No EBV, adenoviral or VZV reactivation or disease was reported. Using interferon-gamma Elispot analysis on post-infusion samples, we identified anti-viral immunity against all viruses including VZV. Three patients (30%) developed grade II-IV acute graft-versus-host disease. Conclusions. This is the first description of the use of a multi-virus-specific T-cell product containing cells specific for VZV after allogeneic HSCT. The T-cell product appears safe in the setting of HSCT and confirms our previous findings regarding CMV control and treatment. A larger study with longer follow-up is required to determine the efficacy of VZV-specific T cells given prophylactically in controlling episodes of herpes zoster and disseminated varicella infection after cessation of prophylactic anti-viral treatment.

• 出版日期2015-10