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Blood, 15 November 2008, Vol. 112, No. 10, pp. 3974-3981.
Prepublished online as a Blood First Edition Paper on September 3, 2008; DOI 10.1182/blood-2008-06-161695.


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Submitted June 6, 2008
Accepted August 18, 2008

Prophylactic infusion of cytomegalovirus specific cytotoxic T-lymphocytes stimulated with Ad5f35pp65 gene modified dendritic cells following allogeneic haemopoietic stem cell transplantation

Kenneth P Micklethwaite, Leighton Clancy, Upinder Sandher, Anna M Hansen, Emily Blyth, Vicki Antonenas, Mary M Sartor, Kenneth F Bradstock, and David J Gottlieb*

Westmead Millennium Institute, The University of Sydney, Sydney, NSW, Australia
Sydney Cellular Therapies Laboratory, Westmead Hospital, Sydney, NSW, Australia
Blood and Marrow Transplant Service, Westmead Hospital, Sydney, NSW, Australia

* Corresponding author; email: david_gottlieb{at}wmi.usyd.edu.au.

Cytomegalovirus (CMV) and its therapy continue to contribute to morbidity and mortality in haemopoietic stem cell transplantation (HSCT). Many studies have demonstrated the feasibility of in-vitro generation of CMV-specific T-cells for adoptive immunotherapy of CMV. Few clinical trials have been performed showing the safety and efficacy of this approach in-vivo. In this study, donor-derived, CMV-specific T-cells were generated for 12 adult HSCT patients by stimulation with dendritic cells transduced with an adenoviral vector encoding the CMV-pp65 protein. Patients received a prophylactic infusion of T-cells after day 28 post-HSCT. There were no infusion related adverse events. CMV DNAemia was detected in 4 patients post-infusion, but was of low level. No patient required CMV-specific pharmacotherapy. Immune reconstitution to CMV was demonstrated by ELISPOT assay in all recipients with rapid increases in predominantly CMV-pp65 directed immunity in 5. Rates of graft versus host disease, infection and death were not increased compared to expected. These results add to the growing evidence of the safety and efficacy of immunotherapy of CMV in HSCT, supporting its more widespread use. This study was registered at www.anzctr.org.au under ID Number: ACTRN12605000213640


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