University of Sydney
Therapeutic infusion of partially HLA-matched third-party virus-specific T cells (VST) for treatment of refractory viral infection in haematopoietic stem cell transplant (HSCT) and renal transplant patients
Barbara Withers2,3, Emily Blyth1,2,3,4, Leighton Clancy1,2, Renee Simms2, Jane Burgess2, Chun Kei Kris Ma2,3, Ken Micklethwaite1,2,3,4, David Gottlieb1,2,3,4.
1Sydney Cellular Therapies Laboratory, Westmead Hospital, Sydney, Australia; 2Centre for Cancer Research, Westmead Millennium Institute, Sydney, Australia; 3Sydney Medical School, University of Sydney, Sydney, Australia; 4Department of Haematology Blood and Marrow Transplant Unit, Westmead Hospital, Sydney, Australia
VST can be efficacious for prophylaxis and treatment of viral infections post-HSCT and organ transplant. Generating VST from the transplant donor has limitations – the donor must be virus seropositive, and the donor’s cells must be accessible. Due to manufacturing time VST are not available in urgent clinical scenarios. Alternate sources of VST are desirable to fill this clinical need.
Aim To assess the safety of treatment with partially HLA-matched VST infusions derived from third-party donors, for refractory Cytomegalovirus (CMV), Epstein Barr Virus (EBV), or adenovirus (ADV) infection in allogeneic HSCT patients
Method A bank of cryopreserved VST was generated from peripheral blood or stem cells of healthy donors. Donor dendritic cells pulsed with viral peptide mixtures were used to stimulate donor mononuclear cells and activated T cells were expanded over 2 weeks. Patients with persistent viral reactivation/infection after 2 weeks of standard therapy were infused with up to four fortnightly doses of 2 x 107/m2 most closely HLA matched CMV, EBV, or adenovirus VST and followed for 12 months to assess infusion safety, GVHD, viral activity, viral immune reconstitution, and antiviral therapy.
Results Preliminary results are available for sixteen patients with median follow-up of 6.6 mths (0.5-14.7). All patients had persistent viral reactivation prior to VST infusion; 14 CMV (2 colitis), 1 EBV, 1 ADV. CMV patients had been treated with a median of 31 days (19-113) anti-viral therapy. Patients received a median of 1.5 infusions (1-4), ranging from a 2-4/6 HLA match. 14 patients were assessed for best viral response post-infusion; 11 CR (PCR negative), 3 PR (> 50% viral titre reduction), ORR 100%. 2 patients were not assessed; 1 EBV patient died 2 weeks post infusion from relapsed disease, 1 CMV patient was virus-negative pre-infusion. One patient with a partial response, died from presumed CMV disease. There was no immediate infusion toxicity. No patients developed acute GVHD, but 3 patients developed chronic GVHD post-infusion. Two renal transplant patients with resistant CMV have been treated off-trial. One patient with refractory CMV and thrombotic microangiopathy had a resolution of symptoms and clearance of CMV after receiving CMV-specific T cells.
Conclusion A high response rate has been demonstrated in patients treated with third-party VST, and no major safety concerns have arisen. Recruitment of solid organ transplant patients with refractory viremia is soon to commence.
NHMRC. Leukaemia Foundation.
15:30 - 17:00
|Stem Cells Bioengineering, and Preclinical Work||Therapeutic infusion of partially HLA-matched third-party virus-specific T cells (VST) for treatment of refractory viral infection in haematopoietic stem cell transplant (HSCT) and renal transplant patients||Room 111-112|