番茄社区

An investigational, off-the-shelf T-cell therapy appears to be effective against six different viral infections that are common in patients who undergo allogeneic hematopoietic cell transplantation (HCT), according to results from a

Posoleucel achieved a partial or complete antiviral response in 95% of 58 adult and pediatric patients infected with one or more of the viruses within 6 weeks of the first infusion with the multi-virus-specific therapy, reported Bilal Omer, MD, of Baylor College of Medicine in Houston, and colleagues in .

"The response rate was quite high, and this is notable because these patients, for the most part, either didn't tolerate conventional therapies, or they had completely failed conventional therapies. So these were patients with pretty significant virus infections," Omer told 番茄社区. "And we were able to treat these patients quickly -- within 24 to 48 hours -- with this off-the-shelf product."

"These infections are a pretty major problem, and while we've made progress with other types of infections, there are just not a lot of effective and safe medications out there for virus infections," Omer continued. "And these patients can get pretty severe virus infections -- usually in the first 3 to 6 months after transplant -- that are the cause of both morbidity and mortality."

Omer explained that some centers have treated these patients using virus-specific T cells that are donor derived. And while effective, "these have to be individually generated for each of these patients, cost a lot of money, and take time to manufacture," limiting the broad adoption of this approach.

In this case, Omer and his colleagues used off-the-shelf T cells that were generated from healthy donors to target six viral viral pathogens in immunocompromised patients: adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus-6 (HHV-6), and JC virus.

Of the 58 treated patients, about half were male (52%), and 18 (31%) were under age 18 at the time of enrollment. Transplant donor sources included matched unrelated (48%), cord blood (16%), mismatched unrelated (16%), haploidentical (10%), and matched related (10%).

Of the 70 evaluable infections treated, the majority were caused by BK virus (39%) or cytomegalovirus (34%), the researchers reported. The vast majority, 46 of the patients, had a single virus upon enrollment while 12 had two or more of the targeted viruses.

The investigators found that by 6 weeks after the initial infusion of posoleucel, partial or complete antiviral responses were achieved in 55 of the entire cohort of 58 patients -- 45 of 46 with one virus infection, and 10 of 12 patients with two or more target viruses.

Regarding specific viruses, antiviral responses were achieved in 10 of 12 patients with adenovirus, all 27 patients with BK virus, 23 of 24 patients with cytomegalovirus, both patients with Epstein-Barr virus, and three of four patients with HHV-6, with viral load reduced in the other patient as well.

The one patient with JC virus had initial stabilization of viral symptoms, which then, however, ultimately progressed, and the patient died.

Omer explained that considering that the patients received T cells from donors with human leukocyte antigen types that were different from those of the individual patients, a main safety concern was graft-versus-host disease (GVHD), which was reported in 13 patients during the trial -- grade 2 in two patients and grade 3 in one patient.

"We really didn't see any severe GVHD," he said. "We saw a couple of patients who got rashes, and those were transient -- they were signs of grade 1 skin GVHD -- but for the most part these were mild and self-limited, and we didn't see any indication that this product would cause moderate or severe GVHD."

There were no reported cases of cytokine release syndrome or other infusion-related toxicities.

The researchers noted that posoleucel is currently being evaluated in three randomized phase III trials for treatment and preventive indications.

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