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EBNA-1 transfer shows promise in avoiding Epstein-Barr virus reactivation
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Transfer of EBNA-1–specific T cells may be an effective method for preventing reactivation of Epstein-Barr virus after stem cell transplantation, according to study results.
Reactivation of Epstein-Barr virus after allogeneic stem cell transplantation can lead to life-threatening infections and trigger post-transplantation lymphoproliferative disease.
This disease may be prevented by Epstein-Barr virus T cells, which has prompted clinicians to pursue cellular immunotherapy as a treatment strategy. Generating antigen-specific T-cell populations in a short time period has proved challenging, according to researchers.
In the current study, Vanya Icheva, MD, of the department of general pediatrics, hematology and oncology at Children’s University Hospital in Tuebingen, Germany, and colleagues describe a rapid protocol for isolating polyclonal Epstein-Barr virus nuclear antigen 1 (EBNA-1)–specific T cells by using an interferon-gamma capture technique.
Ten pediatric and adult patients with Epstein-Barr viremia and/or post-transplantation lymphoproliferative disease after stem cell transplantation underwent adoptive transfer of EBNA-1–specific T cells.
The researchers observed no acute toxicity or graft-versus-host disease higher than grade 2.
After a median 16 days of follow-up, eight of 10 patients demonstrated in vivo expansion of transferred EBNA-1–specific T cells. Researchers reported clinical and virologic response in seven of the 10 patients. Response was defined as decrease of viral load more than 1 log and resolution of post-transplantation lymphoproliferative disease.
Among patients who responded to treatment, no deaths associated with Epstein-Barr virus were reported. Three deaths occurred as a result of other infections, and one patient died from a relapse of the malignancy.
Also, among the responders, three patients were disease-free by the last day of follow-up, which ranged from 2 to 36 months.
Two of 10 patients experienced Epstein-Barr virus-associated mortality. One other patient had ongoing viremia at the final follow-up.
Catherine M. Bollard
“The importance of the study by Icheva et al is that it demonstrates that rapidly generated [Epstein-Barr virus]-specific [cytotoxic T lymphocytes] can control [post-transplantation lymphoproliferative disease] similarly to the traditionally manufactured [Epstein-Barr virus]-specific [cytotoxic T lymphocytes],” Catherine M. Bollard, MD, of Baylor College of Medicine, wrote in an accompanying editorial.
The choice to target immunosubdominant Epstein-Barr antigen EBNA-1 rather than the dominant EBNA3, EBNA2 or LMP2 expressed in post-transplantation lymphoproliferative disease was a novel approach, Bollard said.
“Nevertheless, EBNA-1 was shown to be an effective target and, moreover, promises to broaden the applicability of this immunotherapy to other [Epstein-Barr virus] type 1 and 2 latency tumors (including Burkitt’s lymphoma and Hodgkin’s lymphoma, respectively) because all [Epstein-Barr ]–associated cancers express EBNA-1,” Bollard wrote.
Disclosure: The researchers report no relevant financial disclosures.
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