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Cellular therapy for multiple pathogen infections after hematopoietic stem cell transplant

期刊

CYTOTHERAPY
卷 19, 期 11, 页码 1284-1301

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2017.07.012

关键词

cell- and tissue-based therapy; hematopoietic stem cell transplantation; immune reconstitution; immune system; immunity; lymphocytes

资金

  1. Institute of Clinical Pathology and Medical Research, Westmead Hospital
  2. Australian Government Research Training Program (RTP) Scholarship
  3. National Health and Medical Research Council of Australia
  4. Cancer Council of New South Wales
  5. University of Sydney
  6. Leukaemia Foundation of Australia
  7. Leukemia and Lymphoma Society of the US
  8. Rising Tide Foundation for Clinical Cancer Research Switzerland

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Hematopoietic stem cell transplantation (HSCT) represents the only crative treatment option for many hematological conditions but results in a profoundT-cell deficiency in the post-HSCT period. Infections account for a significant proportion of non-relapse morbidity and mortality, and infections with multiple organisms either simultaneously or at different times after transplant are common. Adoptive cellular therapy (ACT) with prophylactic or therapeutic infusion of donor derived or third-party, pathogen-specific T-cells represents a novel methodology to rapidly reconstitute T-cell mediated immunity in this context. For cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection, clear evidence of efficacy with limited toxicity has been observed, with response rates up to 90%. Infusion of third-party, partially human leukocyte antigen-matched pathogen-specific T-cells have also demonstrated remarkable efficacy with responses seen in up to 70% of patients with resistant CMV, EBV and adenoviral infection. This review addresses the nature of post-HSCT immune deficiency, the common infections that occur in the post-HSCT period and how advances in ACT manufacturing methodologies is allowing for wider implementation of T-cell therapies targeting multiple pathogens in HSCT recipients.

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