Hexaviral Specific T-Cells Used for Prophylaxis and Treatment of Viral Infections in Patients Post Stem Cell Transplant

Abstract

BackgroundViral infections are a significant cause of morbidity and mortality in patients awaiting immune reconstitution post-transplant. Adoptive immunotherapy using virus specific T-cells (VSTs) has been shown to prevent and treat viral infections in immunocompromised hosts. Human Parainfluenza Virus-3 (HPIV3) is a common cause of respiratory illness in these patients and has no approved antiviral therapies.ObjectiveThe primary aim was to determine whether donor derived hexaviral specific T-cells are effective in preventing and treating CMV, EBV, AdV, BK virus, HHV-6, and HPIV3.Patients and MethodsWe studied 7 patients who received hexaviral VSTs after stem cell transplant on a Phase I trial. Virus-specific immunity was measured by IFN-g ELIspot. Viral loads for the targeted viruses were measured at specific time points post VST infusion.ResultsThree patients were treated for active CMV with resolution of viremia. Two patients treated for BK virus had complete resolution of symptoms and viremia, while one had resolution of hemorrhagic cystitis but intermittent viremia and viruria. Two patients were treated prophylactically. One patient remained virus-free, while the other developed EBV viremia requiring a dose of rituximab. Two patients received VSTs under expanded access for emergency treatment – one for disseminated adenoviremia, and the second for HPIV3 pneumonia. These critically ill patients had partial clinical improvements, but VST persistence was likely hindered by steroid use which resulted in incomplete antiviral responses. ELISpot showed evidence of antiviral T-cell activity in 3 of 4 evaluable patients by 3 months post-infusion.ConclusionsPreliminary results show that hexaviral specific VSTs are safe and may be an effective therapy against multiple viral infections. Further studies are warranted to determine if VSTs are effective against active HPIV3 infections. Viral infections are a significant cause of morbidity and mortality in patients awaiting immune reconstitution post-transplant. Adoptive immunotherapy using virus specific T-cells (VSTs) has been shown to prevent and treat viral infections in immunocompromised hosts. Human Parainfluenza Virus-3 (HPIV3) is a common cause of respiratory illness in these patients and has no approved antiviral therapies. The primary aim was to determine whether donor derived hexaviral specific T-cells are effective in preventing and treating CMV, EBV, AdV, BK virus, HHV-6, and HPIV3. We studied 7 patients who received hexaviral VSTs after stem cell transplant on a Phase I trial. Virus-specific immunity was measured by IFN-g ELIspot. Viral loads for the targeted viruses were measured at specific time points post VST infusion. Three patients were treated for active CMV with resolution of viremia. Two patients treated for BK virus had complete resolution of symptoms and viremia, while one had resolution of hemorrhagic cystitis but intermittent viremia and viruria. Two patients were treated prophylactically. One patient remained virus-free, while the other developed EBV viremia requiring a dose of rituximab. Two patients received VSTs under expanded access for emergency treatment – one for disseminated adenoviremia, and the second for HPIV3 pneumonia. These critically ill patients had partial clinical improvements, but VST persistence was likely hindered by steroid use which resulted in incomplete antiviral responses. ELISpot showed evidence of antiviral T-cell activity in 3 of 4 evaluable patients by 3 months post-infusion. Preliminary results show that hexaviral specific VSTs are safe and may be an effective therapy against multiple viral infections. Further studies are warranted to determine if VSTs are effective against active HPIV3 infections.