Addition of varicella zoster virus-specific T cells to cytomegalovirus, Epstein-Barr virus and adenovirus tri-specific T cells as adoptive immunotherapy in patients undergoing allogeneic hematopoietic stem cell transplantation.
OBJECTIVE
Virus-specific T-cell immunotherapy is emerging as a promising management strategy for virus infections in patients after hematopoietic stem cell transplant (HSCT). Here we present outcomes of 10 adult patients who received multi-virus-specific T cells prophylactically after HSCT.


METHODS
Donor-derived cytomegalovirus (CMV)-, Epstein-Barr virus (EBV)-, adenoviral- and varicella zoster virus (VZV)-specific T cells were generated in a single culture and administered to HSCT patients at a dose of 2 × 10(7)/m(2) virus-specific T cells at a median of 63 days post-transplant. Patients were monitored for 12 months for evidence of viral reactivation and graft-versus-host disease.


RESULTS
There was no acute infusion-related toxicity. Six patients developed CMV reactivation after T-cell infusion with a median peak CMV DNA titer of 600 copies per milliliter, and 1 received CMV-specific pharmacotherapy post-infusion. No EBV, adenoviral or VZV reactivation or disease was reported. Using interferon-γ Elispot analysis on post-infusion samples, we identified anti-viral immunity against all viruses including VZV. Three patients (30%) developed grade II-IV acute graft-versus-host disease.


CONCLUSIONS
This is the first description of the use of a multi-virus-specific T-cell product containing cells specific for VZV after allogeneic HSCT. The T-cell product appears safe in the setting of HSCT and confirms our previous findings regarding CMV control and treatment. A larger study with longer follow-up is required to determine the efficacy of VZV-specific T cells given prophylactically in controlling episodes of herpes zoster and disseminated varicella infection after cessation of prophylactic anti-viral treatment.
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia.
Chun K K
CK
Ma
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Blood and Marrow Transplant Unit, Department of Haematology, Westmead Hospital, Sydney, Australia.
Emily
E
Blyth
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, Sydney, Australia.
Leighton
L
Clancy
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, Sydney, Australia.
Renee
R
Simms
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, Sydney, Australia.
Jane
J
Burgess
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, Sydney, Australia.
Rebecca
R
Brown
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia.
Shivashni
S
Deo
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Blood and Marrow Transplant Unit, Department of Haematology, Westmead Hospital, Sydney, Australia.
Kenneth P
KP
Micklethwaite
Faculty of Medicine, University of Sydney, Sydney, Australia; Westmead Millennium Institute, Centre for Cancer Research, Sydney, Australia; Blood and Marrow Transplant Unit, Department of Haematology, Westmead Hospital, Sydney, Australia; Sydney Cell and Gene Therapy Laboratory, Westmead Hospital, Sydney, Australia. Electronic address: david.gottlieb@sydney.edu.au.
David J
DJ
Gottlieb
D000258:Adenovirus Infections, Human / Q000517:prevention & control; D000260:Adenoviruses, Human / Q000276:immunology; D000328:Adult; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control* / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006562:Herpes Zoster / Q000276:immunology / Q000517:prevention & control; D014645:Herpesvirus 3, Human / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous; D014775:Virus Activation; D014777:Virus Diseases / Q000517:prevention & control*; D055815:Young Adult
D007371:Interferon-gamma
T cell therapy; adoptive immunotherapy; haematopoietic stem cell transplant; immune reconstitution; varicella zoster–specific T cells