Wei Jiang1,2, Barbara Withers1,2,3, Gaurav Sutrave1,2,4, Leighton E Clancy2,5, Michelle I Yong6,7,8, Emily Blyth9,10,11,12. 1. Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia. 2. Westmead Institute of Medical Research, University of Sydney, Sydney, Australia. 3. St Vincent's Hospital, Darlinghurst, Australia. 4. BMT and Cell Therapies Program, Westmead Hospital, Sydney, Australia. 5. Sydney Cellular Therapies Laboratory, Westmead, Australia. 6. National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Australia. 7. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. 8. The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia. 9. Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia. emily.blyth@sydney.edu.au. 10. Westmead Institute of Medical Research, University of Sydney, Sydney, Australia. emily.blyth@sydney.edu.au. 11. St Vincent's Hospital, Darlinghurst, Australia. emily.blyth@sydney.edu.au. 12. BMT and Cell Therapies Program, Westmead Hospital, Sydney, Australia. emily.blyth@sydney.edu.au.
Abstract
PURPOSE OF REVIEW: Infectious diseases contribute significantly to morbidity and mortality in recipients of allogeneic haematopoietic stem cell transplantation (aHSCT), particularly in the era of highly immunosuppressive transplant regimens and alternate donor transplants. Delayed cellular immune recovery is a major mechanism for the increased risk in these patients. Adoptive cell therapy with ex vivo manipulated pathogen-specific T cells (PSTs) is increasingly taking its place as a treatment strategy using donor-derived or third party-banked cells. RECENT FINDINGS: The majority of clinical trial data in the form of early-phase studies has been in the prophylaxis or treatment of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus (AdV). Advancements in methods to select and enrich PSTs offer the opportunity to target the less common viral pathogens as well as fungi with this technology. Early clinical studies of PSTs targeting polyomaviruses (BK virus and JC virus), human herpesvirus 6 (HHV6), varicella zoster virus (VZV) and Aspergillus spp. have shown promising results in small numbers of patients. Other potential targets include herpes simplex virus (HSV), respiratory viruses and other invasive fungal species. In this review, we describe the burden of disease of this wider spectrum of pathogens, the progress in the development of manufacturing capability, early clinical results and the opportunities and challenges for implementation in the clinic.
PURPOSE OF REVIEW: Infectious diseases contribute significantly to morbidity and mortality in recipients of allogeneic haematopoietic stem cell transplantation (aHSCT), particularly in the era of highly immunosuppressive transplant regimens and alternate donor transplants. Delayed cellular immune recovery is a major mechanism for the increased risk in these patients. Adoptive cell therapy with ex vivo manipulated pathogen-specific T cells (PSTs) is increasingly taking its place as a treatment strategy using donor-derived or third party-banked cells. RECENT FINDINGS: The majority of clinical trial data in the form of early-phase studies has been in the prophylaxis or treatment of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus (AdV). Advancements in methods to select and enrich PSTs offer the opportunity to target the less common viral pathogens as well as fungi with this technology. Early clinical studies of PSTs targeting polyomaviruses (BK virus and JC virus), human herpesvirus 6 (HHV6), varicella zoster virus (VZV) and Aspergillus spp. have shown promising results in small numbers of patients. Other potential targets include herpes simplex virus (HSV), respiratory viruses and other invasive fungal species. In this review, we describe the burden of disease of this wider spectrum of pathogens, the progress in the development of manufacturing capability, early clinical results and the opportunities and challenges for implementation in the clinic.
Entities:
Keywords:
Adoptive immunotherapy; Fungus-specific T cells; Haemopoietic stem cell transplantation; Immune reconstitution; Pathogen-specific T cells; Virus-specific T cells
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