16 January 2023

A T-cell therapy has shown promising results for preventing viral infections after stem cell transplant, researchers report.

Patients with blood cancers and other haematological disorders may receive allogeneic stem cell transplantation to try and cure their disease. However, this procedure leaves the patient at risk of dangerous viral infections while their immune system is reconstituted.

What’s more, treatments for these viral infections have many limitations, as Dr Bilal Omer of the Texas Children’s Hospital, USA, explains: “Traditional antiviral medications often have difficult-to-tolerate toxicities, such as myelosuppression or kidney injury. Moreover, their efficacies are limited in this patient population, and treatment resistance develops relatively easily.”

A research team carried out a phase II clinical trial to measure the safety and efficacy of an investigational therapy using donor T cells called posoleucel. The team was led by Dr Omer and Dr Thomas Pfeiffer from Washington University School of Medicine in St. Louis.

Posoleucel is an allogenic T-cell therapy designed to target six of the most common viruses after allogeneic stem cell transplantation: adenovirus, BK virus, cytomegalovirus (CMV), Epstein-Barr virus, human herpes virus 6, and JC virus.

58 adult and paediatric patients were recruited to the study, all of whom had one of these six viral infections and were either unresponsive to or unable to tolerate conventional therapies.

Results of the study were published in Clinical Cancer Research. A partial or complete response was observed in 95% of the patients within six weeks of infusion.

The amount of circulating virus was reduced by an average of 97%. For the 12 patients who experienced multiple viral infections, 83% had a response against the viruses.

Dr Omer commented: “The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections. 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.

“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.”

Phase III trials of posoleucel are now underway for both therapeutic and preventative indications.

 

Source:

Pfeiffer T, Tzannou I, Wu M, Ramos C, Sasa G, Martinez C, Lulla P, Krance RA, Scherer L, Ruderfer D, Naik S, Bocchini C, Fraser IP, Patel B, Ward D, Wang T, Heslop HE, Leen AM, Omer B. (2023) “Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting.” Clinical Cancer Research, doi: 10.1158/1078-0432.CCR-22-2415

Link: https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-2415/712758/Posoleucel-an-Allogeneic-Off-the-Shelf-Multivirus

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