Hexaviral specific T-cells targeting parainfluenza, CMV, EBV, adenovirus, HHV6 and BKV used for prophylaxis and treatment of viral infections in patients post stem cell transplant

Abstract

Background & Aim Viral infections are a significant cause of morbidity and mortality in patients with primary immunodeficiency disorders and following hematopoietic stem cell transplantation. 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 severe respiratory illness in immunocompromised patients and has no approved antiviral therapies and has not previously been used as a target for T cell therapeutics. 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. Methods, Results & Conclusion Patients and Methods This was a “first in man” study where we studied the antiviral effect in 8 patients who received hexa-valent VSTs after stem cell transplant on a Phase I trial. Assessment of virus-specific immunity was measured by IFN-gamma ELIspot. Viral loads for the primary targeted viruses were measured at specific time points post VST infusion. Results Three patients were treated for active CMV and had resolution of viremia. Two patients treated for active BK virus had complete resolution of symptoms and viremia, while one had resolution of hemorrhagic cystitis but fluctuating viral loads in the blood and urine. Two patients were treated prophylactically. One patient did not develop any infections, while the other developed EBV viremia requiring rituximab. Two patients received VSTs under expanded access for emergency treatment – 1 patient was treated for disseminated adenoviremia and the second patient was treated for HPIV3 pneumonia. These critically ill patients demonstrated partial clinical improvements, but both died (one of progressive adenovirus, and the other of gram negative sepsis). VST persistence was likely hindered by concomitant 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, with in vivoVST expansion detectable in 2 patients. Conclusions Preliminary results show that hexaviral specific VSTs are safe and may be effective in preventing and treating multiple viral infections. Further studies are warranted to determine if VSTs are effective against active HPIV3 infections.