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Publication Detail
Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Izotova N, Rivat C, Baricordi C, Blanco E, Pellin D, Watt E, Gkazi AS, Adams S, Gilmour K, Bayford J, Booth C, Gaspar HB, Thrasher AJ, Biasco L
  • Publication date:
    12/03/2021
  • Pagination:
    1622
  • Journal:
    Nat Commun
  • Volume:
    12
  • Issue:
    1
  • Status:
    Published
  • Country:
    England
  • PII:
    10.1038/s41467-021-21834-9
  • Language:
    eng
Abstract
Our mathematical model of integration site data in clinical gene therapy supported the existence of long-term lymphoid progenitors capable of surviving independently from hematopoietic stem cells. To date, no experimental setting has been available to validate this prediction. We here report evidence of a population of lymphoid progenitors capable of independently maintaining T and NK cell production for 15 years in humans. The gene therapy patients of this study lack vector-positive myeloid/B cells indicating absence of engineered stem cells but retain gene marking in both T and NK. Decades after treatment, we can still detect and analyse transduced naïve T cells whose production is likely maintained by a population of long-term lymphoid progenitors. By tracking insertional clonal markers overtime, we suggest that these progenitors can support both T and NK cell production. Identification of these long-term lymphoid progenitors could be utilised for the development of next generation gene- and cancer-immunotherapies.
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