In a phase II study reported in the Journal of Clinical Oncology, Tzannou et al found that use of off-the-shelf, broad-coverage, adoptively transferred, virus-specific T cells was feasible and effective in treating viral infections in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT).
In the study, a bank of adoptively transferred virus-specific T cells generated from eligible third-party donors was developed that recognized Epstein-Barr virus (EBV), adenovirus (AdV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV-6). Virus-specific T-cell infusions were given to 38 patients with 45 infections.
Of the 38 patients, 32 had acute myeloid leukemia/myelodysplastic syndrome (n = 20), acute lymphoblastic leukemia (n = 9), or lymphoma/multiple myeloma (n = 3), and 6 had nonmalignant conditions. A total of 23 patients received a single infusion, 11 received 2 infusions, and 4 had 3 infusions.
Response Rates and Toxicity
A single virus-specific T-cell infusion produced complete or partial response in 92% of patients, including response in 100% of the 16 patients with BKV infections, 94% of the 17 patients with CMV infections, 71% of the 7 patients with AdV infections, 2 of the 2 patients with EBV infections, and 2 of 3 patients with HHV-6 infections. Clinical benefit was achieved in each of the 31 patients treated for 1 infection and each of the 7 patients treated for multiple infections. Complete resolution of gross hematuria by week 6 was observed in 13 of 14 patients treated for BKV-associated hemorrhagic cystitis.
Infusions were well tolerated. Apart from an isolated fever in 1 patient within 24 hours of infusion, no immediate toxicities were observed, and no patients developed cytokine-release syndrome. Two patients had de novo graft-vs-host disease, both grade 1. Tracking of the infused product indicated that functional virus-specific T cells persisted for up to 12 weeks.
The investigators concluded: “The use of banked [virus-specific T cells] 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. Furthermore, the multispecificity of the [virus-specific T cells] ensures extensive antiviral coverage, which facilitates the treatment of patients with multiple infections.”
The study was supported by grants from the National Heart, Lung, and Blood Institute, Conquer Cancer Foundation/ASCO, Dan L. Duncan Cancer Center, and National Institutes of Health.
Bilal Omer, MD, of the Center for Cell and Gene Therapy, Baylor College of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
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