Greater than the sum of their parts: Combination strategies for immune regeneration following allogeneic hematopoietic stem cell transplantation Journal Article

   


Authors: Dudakov, J. A.; van den Brink, M. R. M.
Article Title: Greater than the sum of their parts: Combination strategies for immune regeneration following allogeneic hematopoietic stem cell transplantation
Abstract: Cytoreductive conditioning regimes designed to allow for successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) paradoxically are also detrimental to recovery of the immune system in general but lymphopoiesis in particular. Post-transplant immune depletion is particularly striking within the T cell compartment which is exquisitely sensitive to negative regulation, evidenced by the profound decline in thymic function with age. As a consequence, regeneration of the immune system remains a significant unmet clinical need. Over the past decade studies have revealed several promising therapeutic strategies to address ineffective lymphopoiesis and post-transplant immune deficiency. These include the use of cytokines such as IL-7, IL-12 and IL-15; growth factors and hormones like keratinocyte growth factor (KGF), insulin-like growth factor (IGF)-1 and growth hormone (GH); adoptive transfer of ex vivo-generated precursor T cells (pre-T) and sex steroid ablation (SSA). Moreover, recently several novel approaches have been proposed to generate whole thymii ex vivo using stem cell technologies and bioscaffolds. Increasingly, however, when transferred to the clinic, these strategies alone are not sufficient to restore thymopoiesis in all patients leading to the potential of combination strategies as a way to reign in non-responders. Synergistic enhancement in combination may be due to differential targets may therefore be effective in improving clinical outcomes in the transplant settings as well as in other lymphopenic states induced by high dose chemotherapy/radiation therapy or HIV, and may also be useful in improving responses to vaccination and augmenting anti-tumor immunotherapy. © 2011 Elsevier Ltd. All rights reserved.
Keywords: cancer chemotherapy; leukemia; cancer radiotherapy; cd8+ t lymphocyte; cell proliferation; interleukin 7; growth hormone; thymus; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; adoptive transfer; cell regeneration; somatomedin c; flt3 ligand; t cell depletion; lymphopoiesis; ghrelin; interleukin 12; interleukin 15; keratinocyte growth factor; immune regeneration; allogeneic hematopoietic stem cell trans-plantation
Journal Title: Best Practice and Research: Clinical Haematology
Volume: 24
Issue: 3
ISSN: 1521-6926
Publisher: Elsevier Inc.  
Date Published: 2011-09-01
Start Page: 467
End Page: 476
Language: English
DOI: 10.1016/j.beha.2011.05.003
PROVIDER: scopus
PMCID: PMC3176434
PUBMED: 21925100
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-80052991999&partnerID=40&md5=f89ed206a44b33a0a1145b0c578dc317
Notes: --- - "Export Date: 2 November 2011" - "CODEN: BPRCA" - "Source: Scopus"
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MSK Authors
  1. Marcel R M Van Den Brink
    616 Van Den Brink
  2. Jarrod Andrew Dudakov
    58 Dudakov
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