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21-08-2017 | Oncology | News | Article

Off-the-shelf solution targets multiple post-allogeneic HSCT viral infections

medwireNews: Researchers have used pre-prepared virus-specific T cells (VSTs) to successfully treat five viral infections commonly seen in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT).

The off-the-shelf pentavalent T-cell lines were created using blood from healthy seropositive donors and included 12 viral antigens from Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6).

Researchers report in the Journal of Clinical Oncology that after one VST infusion, 91.9% of 37 patients had a complete or partial response by week 6.

Bilal Omer and colleagues, from the Baylor College of Medicine in Houston, Texas, USA, developed a bank of 59 VST lines, of which 23 were matched by human leukocyte antigen (HLA) type to 38 patients who had undergone allogeneic HSCT.

All of the patients included in the phase II trial had drug-refractory infections or diseases associated with at least one of the five viruses included in the VSTs.

The cumulative response rate (complete and partial responses) was 100% for the 16 patients undergoing treatment for BKV and for the two patients with EBV infection. It was 94.1% for the 17 patients with CMV, 71.4% for the seven patients with AdV, and 66.7% for the three patients being treated for HHV-6.

The researchers point out that all seven patients with two viral infections had clinical benefit for both infections with a single infusion.

Furthermore, 13 of 14 patients treated for BKV-associated hemorrhagic cystitis experienced complete resolution of gross hematuria by week 6, which is notable because there are currently no antiviral drugs approved to treat BKV, Omer et al remark.

Seven patients experienced a recurrence of their original viral infection at a median of 10 weeks, which was successfully treated with one (n=5) or two (n=1) additional infusions.

The researchers showed that functional VSTs persisted for up to 12 weeks and also found that there was no correlation between viral load reduction and HLA matching in patients who received low (1–3 alleles matched) versus high (4–8 matching alleles) HLA-matched VST lines.

Moreover, the treatment was well tolerated, with no cases of cytokine release syndrome and only two cases of de novo graft-versus-host disease (grade 1) occurring.

“Although a randomized trial will be required to definitively assess the value of banked VSTs, this study strongly suggests that off-the-shelf multiple-virus–directed VSTs are a safe and effective broad-spectrum approach to treat severe viral infections after HSCT,” Omer and team conclude.

They add: “These VSTs can be rapidly and cost-effectively produced in scalable quantities with excellent long-term stability, which facilitates the broad implementation of this therapy.

“More widespread and earlier use of this modality could minimize both drug-related and virus-associated complications and thereby decrease treatment-related mortality in recipients of allogeneic HSCT.”

By Laura Cowen

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