Third-Party Virus-Specific T-Cell Infusion for the Treatment of Refractory Viral Infections: Results from PBMTC SUP1701

Virus-specific T-cells from third party or transplant donors for treatment of EBV lymphoproliferative diseases arising post hematopoietic cell or solid organ transplantation

“…In this light, an important finding emerging from the trials summarized in Tables 1 , 2 is that the initial response rates (CR +PR) achieved with HCT donor-derived and 3 rd party donor-derived EBVCTLs are strikingly similar. This is shown in Tables 1 , 2 for trials at several centers that treated EBV+ lymphomas emerging post HCT with EBV-specific T-cells generated from HCT ( 10 , 24 , 31 , 36 , 37 , 39 ) or 3 rd party donors ( 11 , 27 , 28 , 31 , 35 , 44 – 46 , 48 , 50 , 57 – 63 ) by the in vitro culture methods previously described. Patients treated with EBVCTLs isolated directly by immunomagnetic separation of IFNγ+ T-cells after brief sensitization with pools of immunogenic EBV peptides from latency 1, 2 and 3 proteins ( 36 – 39 ) have also achieved similar response rates even though the doses of EBVCTLs administered were 1-2 log 10 lower.…”

“…Because most trials of adoptive therapy have excluded patients with grade II-IV acute GVHD, the effects of GVHD or its treatment on the outcome of adoptive therapy are unclear. However, pre-transplant conditioning that included ATG has been cited not only as a risk factor for development of EBVPTLD ( 13 ) but also a risk factor for a lower response rate to 3 rd party multivirus specific T-cells ( 63 ). Ongoing treatment with systemic corticosteroids has been variably associated with lower responses to virus-specific T-cells in patients treated for CMV and adenovirus infections, but too few patients on steroid have been treated for EBVPTLD to clearly assess significance.…”