T-Cell Injections Effective, Safe for Severe Viral Infections After HSCT

Virus-specific T-cells (VSTs) are a safe and effective treatment for patients who develop severe, drug-resistant viral infections following an allogenic hematopoietic stem-cell transplantation (HSCT), according to a recent study.

To improve cure rates in patients receiving HSCT, efforts to decrease treatment-related mortality from severe viral infections are needed. Adoptively transferred VSTs generated from eligible, third-party donors could provide broad antiviral protection to recipients of HSCT as an immediately available, off-the-shelf product.
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In their study, the researchers assessed 38 patients who had undergone HSCT and had a total of 45 infections. The researchers developed a bank of VSTs—derived from healthy seropositive donors—to treat patients with Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and/or human herpesvirus 6 (HHV-6). These VSTs were subsequently administered to patients.

Results indicated that a single injection had produced a cumulative complete or partial response rate of 92% overall. All patients with EBV (n = 2) and BKV (n= 16) had achieved a complete or partial response rate. About 94% of those with CMV (n = 17), 71%  with AdV (n = 7), and 67% with HHV-6 (n = 3) had achieved a response rate.

The clinical benefit was achieved in 31 patients treated for 1 infection and in 7 patients treated for multiple co-infections. Additionally, 13 of 14 patients treated for BKV-associated hemorrhagic cystitis had experienced complete resolution of gross hematuria by week 6.

Ultimately, the researchers found that the infusions were safe and only observed 2 occurrences of grade 1 de novo graft vs host disease. VST tracking by epitope profiling revealed persistence of functional VSTs of third-party origin for up to 12 weeks.

“The use of banked VSTs is a feasible, safe, and effective approach to treat severe and drug-refractory infections after HSCT, including infections from two viruses (BKV and HHV-6) that had never been targeted previously with an off-the-shelf product,” the researchers concluded. “Furthermore, the multispecificity of the VSTs ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections.”

—Christina Vogt

Reference:

Tzannou I, Papadopoulou A, Naik S, et al. Off-the-shelf virus-specific T cells to treat BK virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, and adenovirus infections after allogeneic hematopoietic stem-cell transplantation [Published online August 7, 2017]. J Clin Oncol. doi:10.1200/JCO.2017.73.0655.