Negative depletion of α/β+ T cells and of CD19+ B lymphocytes: A novel frontier to optimize the effect of innate immunity in HLA-mismatched hematopoietic stem cell transplantation

Franco Locatelli, Aurelie Bauquet, Giuseppe Palumbo, Francesca Moretta, Alice Bertaina

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57 Citations (Scopus)

Abstract

In recent years, infusion of T-cell depleted hematopoietic stem cells from an HLA-haploidentical relative has been shown to represent a suitable and effective, alternative option in patients in need of an allograft who lack an HLA-identical relative. In particular, this type of allograft is associated with the enormous advantage of offering an immediate transplant treatment to virtually all pediatric patients without an HLA-matched donor, whether related or unrelated, or a suitable umbilical cord blood unit. Several studies have shown that in patients given a T-cell depleted transplant relevant part of the anti-leukemia effect is mediated by alloreactive (i.e. KIR/HLA mismatched) Natural Killer cells originated from donor hematopoietic stem cells. After infusion of positively selected hematopoietic stem cell, fully functioning Natural Killer cells emerge in the recipient peripheral blood, persisting over time, only several weeks after the allograft. We have developed a new method of T-cell depletion (based on the physical elimination of mature T cells carrying α and β chains of the T-cell receptor), which permits to maintain mature donor-derived alloreactive Natural Killer cells and γδ+ T cells in the graft. We, thus, started a formal study in children with hematological disorders aimed at evaluating the safety and efficacy of this approach. Preliminary results on 60 children transplanted so far after this type of graft manipulation are particularly promising.

Original languageEnglish
Pages (from-to)21-23
Number of pages3
JournalImmunology Letters
Volume155
Issue number1-2
DOIs
Publication statusPublished - Sep 2013

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Hematopoietic Stem Cell Transplantation
Innate Immunity
B-Lymphocytes
T-Lymphocytes
Hematopoietic Stem Cells
Natural Killer Cells
Allografts
Transplants
Tissue Donors
T-Cell Antigen Receptor
Fetal Blood
Leukemia
Pediatrics
Safety

Keywords

  • γδ T cells
  • Allogeneic hematopoietic stem cell transplantation
  • NK cell maturation
  • Selective T-cell depletion

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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abstract = "In recent years, infusion of T-cell depleted hematopoietic stem cells from an HLA-haploidentical relative has been shown to represent a suitable and effective, alternative option in patients in need of an allograft who lack an HLA-identical relative. In particular, this type of allograft is associated with the enormous advantage of offering an immediate transplant treatment to virtually all pediatric patients without an HLA-matched donor, whether related or unrelated, or a suitable umbilical cord blood unit. Several studies have shown that in patients given a T-cell depleted transplant relevant part of the anti-leukemia effect is mediated by alloreactive (i.e. KIR/HLA mismatched) Natural Killer cells originated from donor hematopoietic stem cells. After infusion of positively selected hematopoietic stem cell, fully functioning Natural Killer cells emerge in the recipient peripheral blood, persisting over time, only several weeks after the allograft. We have developed a new method of T-cell depletion (based on the physical elimination of mature T cells carrying α and β chains of the T-cell receptor), which permits to maintain mature donor-derived alloreactive Natural Killer cells and γδ+ T cells in the graft. We, thus, started a formal study in children with hematological disorders aimed at evaluating the safety and efficacy of this approach. Preliminary results on 60 children transplanted so far after this type of graft manipulation are particularly promising.",
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AU - Palumbo, Giuseppe

AU - Moretta, Francesca

AU - Bertaina, Alice

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