Allogeneic Viral Specific T Cells Are Safe and Can be Efficient in the Treatment of Infections in Solid Organ Transplant Recipients

Abstract

Introduction Recipients of solid organ transplant (SOT) are at risk of viral infection and development of viral-driven malignancy (EBV-PTLD) due to immunosuppressive medications to prevent organ rejection. Treatments are limited by poor efficacy and organ toxicity, and reduction in immunosuppression to enable the patient's immune system fight the infection risks organ rejection. Allogeneic viral specific T-cells (VST) have been used to treat viral infections after stem cell transplant, and here we evaluated VST for the treatment of CMV, ADV, EBV-PTLD and BK in six SOT (heart, liver, kidney, lung) recipients. Methods Clinical descriptors of diagnosis, therapy and viral load in patients are presented. Results At the time of VST infusion, patients were a median of 16 years of age (range 2 - 69 years) with an average of 5 years post-SOT. Patients were on one or more immunosuppressive medications, including on Tacrolimus (3), prednisolone (4) and hydrocortisone (2). The majority of patients have received multiple monthly infusions to treat viral disease (range of 1-8). The HLA match between the VST unit and recipient ranged from 4/10 to 6/10. Class I matches were from 0/6 to 3/6, and Class II matches from 1/4 to 4/4. The treatment was safe with no serious adverse events observed. All patients had stable viral disease or a clinical response following VST infusion. The response was sustained over multiple infusions except one patient who showed a response to CMV after the first infusion but not after the second. This patient had a 5/10 match (3 class I and 2 class II match), liver transplant, and Tacrolimus treatment. Other patients with the same degree of match, virus infection, or immunosuppressant had continued responses and were not likely the cause of the loss of response and therefore could be immune mediated rejection of the VST. The presence of cells responding to viral peptides was evaluated in PBMC from five patients using IFNg ELIspot. Compared to pre-infusion, there was a higher number of responding cells circulating at up to 4 weeks post-VST infusion for CMV and ADV with 129 to 852 spots 1 × 105 peripheral blood mononuclear cells in response to viral peptide. Neither of the 2 kidney recipients treated for BK and EBV, or EBV-PTDL had an increase spots over background despite showing a clinical response suggesting that the cells contributing to the clinical response were in the tissues or still active despite being below the level of detection of 10 spots per 1 × 105 peripheral blood mononuclear cells. Conclusion Infusion of allogeneic VST to SOT recipients suffering from viral infections was safe and resulted in clinical responses in recipients and may offer additional treatment options to this group of patients. Further data are needed to correlate clinical response with VST activity and persistence to optimize future infusion schedules and allow for optimal dosing.