Human Herpes simplex virus
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An off-the-shelf T-cell therapy has successfully treated drug-resistant viral infections in 95 percent of patients undergoing allogeneic stem cell transplants, according to final results from an open label Phase II trial.

Patients that have received allogeneic bone marrow transplants have their immune system suppressed so that their body doesn’t reject the transplant. However, in around 90% of these patients, this allows previously latent viruses in the body to reactivate, causing life-threatening infections. The standard of care consists of traditional antiviral medicines, however, these drugs can produce side effects such as kidney injury, and viruses can build up resistance.

The study, which was sponsored by the biotech company AlloVir and published today in Clinical Cancer Research, tested the ability of AlloVir’s donor-derived T-cell therapy posoleucel to treat drug-resistant viral infections in these patients until their new, grafted immune system kicks in.

The group, led by senior author Bilal Omer, pediatric hematologist-oncologist at Texas Children’s Hospital, previously published promising interim results in the first 38 patients from the trial in 2017. Today’s publication unveiled the full results from all 58 enrolled patients.

According to the final analysis, posoleucel reduced the viral load in 55 out of 58 patients (95 percent) in the trial, treating their infections. The viral infections targeted by the therapy included adenovirus, BK virus, CMV, Epstein-Barr virus, human herpes virus and JC virus. Twelve patients in the trial had more than one infection at the same time, and 10 of them (83 percent) responded to the T-cell therapy.

While thirteen patients experienced graft-versus-host disease (GvHD)—where the grafted cells damage the patient’s healthy tissues—only four were linked to the T-cell therapy, and most cases were mild.

“Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population,” said Thomas Pfeiffer, the first author of the study and an assistant professor of pediatrics at Washington University School of Medicine in St. Louis, in a public statement.

“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added Omer. “It was quite impressive how quickly patients could be treated.”

AlloVir’s posoleucel consists of T cells sourced from healthy donors. The T cells are grown in the lab and only the ones targeted to viruses, called virus-specific T cells (VSTs), are used in the therapy. As the VSTs are focused on hunting for viral antigens, they are less likely to cause GvHD than other T-cell therapies such as CAR-T therapies approved to treat blood cancer.

Unlike CAR-T therapies, which are derived from the patient’s own cells, posoleucel’s T cells are not genetically engineered. Instead, they are taken from donors that have been exposed to the viral infection of interest. Being sourced from donors also means posoleucel can be given to patients faster than CAR-T cells.

“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” stated Omer. “Additionally, posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections, resulting in excruciating pain for patients.”

This trial’s results are only an early indication of the potential of posoleucel as there was no control group. AlloVir is developing posoleucel in several ongoing placebo-controlled Phase II and Phase III trials to test its effectiveness in preventing and treating viral infections in different transplant patients. The Phase III trials are enrolling patients this year, and the first results could come out in 2024.

VSTs have been in development for many years, and the EU approval of Atara Therapeutics’ Ebvallo last year for a rare form of virus-linked cancer indicates that this technology is on the cusp of entering the mainstream. AlloVir’s treatment could lead the way in tackling a wide range of viral infections in patients that can’t be helped with conventional antivirals.

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