Broad-spectrum T cells appear to effectively treat the viral infections that commonly follow an hematopoietic stem cell transplant, researchers reported.
In a small clinical trial, infusions of T cells were associated with a 94% response rate when used to treat patients with up to four viral infections, according to Ann Leen, PhD, of the Baylor College of Medicine in Houston, and colleagues.
The so-called virus-specific T cells, or VSTs, were safe in all patients, Leen and colleagues reported online in Science Translational Medicine.
The researchers cautioned that the study was small -- just 11 patients -- and cannot demonstrate definitively that the transplanted cells were responsible for curing the viral infections.
"Without a large-scale randomized controlled study," they noted, "it is not possible to definitively attribute clinical responses ... to the infused cells," since low-level transient viremia is often seen in the wake of an hematopoietic stem cell transplant and clears up without intervention.
But the phase I study offers preliminary evidence that the approach will work and is safe, they argued.
Opportunistic viral infections are common in the wake of an hematopoietic stem cell transplant for such diseases as acute lymphoblastic leukemia and non-Hodgkin's lymphoma.
For many viruses, there are no specific treatments, and while T cell approaches have been shown to work in some cases, making the cells is a long, complicated, and costly process.
Leen and colleagues derived T cells specific to five viruses -- cytomegalovirus, adenovirus, Epstein-Barr virus, BK virus, and human herpesvirus 6 -- by stimulating peripheral blood mononuclear cells with overlapping peptide libraries of viral antigens.
Of the 48 cell lines they created, 14 had activity in the lab against all five viruses and, importantly, none showed alloreactivity against the recipients, Leen and colleagues reported.
The number of viruses recognized by a given cell line was correlated with the donors' age, they reported, possibly a reflection of exposure to a larger number of pathogens in older donors.
The VST lines -- almost exclusively CD3-positive T cells -- took between nine and 11 days to be created and expanded from the original cell population, they said.
To test them, the researchers infused between five and 20 million cells into 11 patients, eight of them to treat existing infections -- some multiple -- and three as prophylaxis. The investigators reported that they saw no correlation between the number of cells given to a patient and either safety or antiviral activity.
All of the patients who got the cells prophylactically -- between 38 and 43 days after transplant -- remained free of infection by all of the viruses for more than 3 months, Leen and colleagues reported.
Of the remaining eight, two had one virus, three patients were treated for two, another two had three viruses, and one participant was treated for four viruses.
The response rate for the 18 infections (involving five different viruses) was high: 94% with 15 complete and two partial responses, the researchers reported, and in all cases, viral clearance was associated with an increase in T cells directed against the infecting pathogen.
"Notably," Leen and colleagues reported, "these benefits were obtained without toxicities," such as severe graft-versus-host disease.