Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation

Abstract

• Banked third-party virusspecific T cells can safely and rapidly treat severe or intractable viral infections after HSCT.Virus-specific T cell (VST) lines could provide useful antiviral prophylaxis and treatment of immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus (EBV), cytomegalovirus, or adenovirus. A total of 18 lines were administered to 50 patients with severe, refractory illness because of infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks postinfusion were 74.0% (95% CI, 58.5%-89.5%) for the entire group (n 5 50), 73.9% (95% CI, 51.2% -96.6%) for cytomegalovirus (n 5 23), 77.8% for adenovirus (n 5 18), and 66.7% (95% CI, 36.9%-96.5%) for EBV (n 5 9). Only 4 responders had a recurrence or progression. There were no immediate infusionrelated adverse events, and de novo graft-versus-host disease developed in only 2 patients. Despite the disparity between the lines and their recipients, the mean frequency of VSTs increased significantly postinfusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party VSTs is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. This study is registered at www.clinicaltrials.gov as NCT00711035. (Blood. 2013;121(26):5113-5123)

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

“…Potential solution in this scenario is the so called "third party bio-banks" of VSTCs where they can be selected by HLA haplotypes [105]. The first multicenter trial of ATCT with cells obtained from banked third-party VSTCs for the treatment of refractory viral infections after HSCT was reported by Leen et al in 2013 [106]. The Authors developed a bio-bank of 32 virus-specific lines from volunteers with common HLA polymorphisms against Epstein-Barr virus, CMV, or adenovirus.…”

EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT

“…Here, today's challenges are to make an at least partially HLA-compatible, highly purified T-cell product available in a timely manner for every patient in need. 45 …”

Umbilical cord blood graft engineering: challenges and opportunities

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