Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: Rationale, strategies and perspectives

Giuseppina Li Pira, Stefano Di Cecca, Mauro Montanari, Lorenzo Moretta, Fabrizio Manca

Research output: Contribution to journalArticle

Abstract

Hemopoietic stem cell transplantation (HSCT) is a standard procedure for treatment of malignant and non-malignant hematological diseases. HSCT donors include HLA-identical siblings, matched or mismatched unrelated donors and haploidentical related donors. Graft-versus-host disease (GvHD), mediated by donor alloreactive T-cells in the graft, can be triggered by minor histocompatibility antigens in HLA-identical pairs, by alleles at loci not considered for MUD-matching or by the mismatched haplotype in haplo-HSCT. Therefore, removal of donor T-cells, that contain the alloreactive precursors, is required, but T-cell depletion associates with opportunistic infections and with reduced graft-versus-leukemia effect. Selective T-cell depletion strategies have been introduced, like removal of αβ T-lymphocytes and of naive T-cells, two subsets including the alloreactive precursors, but the ultimate goal is specific removal of alloreactive T-cells. Here we review the different approaches to deplete alloreactive T-cells only and discuss pros and cons, specificity, efficiency and efficacy. Combinations of different methods and innovative approaches are also proposed for depleting specific alloreactive T-cells with high efficiency.

Original languageEnglish
JournalBlood Reviews
DOIs
Publication statusAccepted/In press - 2016
Externally publishedYes

Keywords

  • Allodepletion
  • Alloreactive T-cells
  • Cell manipulation
  • Graft-versus-host disease
  • Hemopoietic stem cell transplantation
  • T-cell activation

ASJC Scopus subject areas

  • Hematology
  • Oncology

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