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Publication Detail
Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans.
  • Publication Type:
    Journal article
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  • 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
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    Nat Commun
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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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