Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: rationale, strategies and perspectives. Issue 4 (July 2016)

• Record Type: Journal Article
• Authors: Li Pira, Giuseppina; Di Cecca, Stefano; Montanari, Mauro; Moretta, Lorenzo; Manca, Fabrizio
• Is Part Of: Blood reviews. Volume 30:Issue 4(2016:Jul.)
• Page Start: 297
• Page End: 307
• Publication Date: 2016-07
• Subjects: Hemopoietic stem cell transplantation -- Graft-versus-host disease -- Alloreactive T-cells -- T-cell activation -- Allodepletion -- Cell manipulation; Hematology -- Periodicals; Hematology -- Periodicals; Hématologie -- Périodiques; Hematology; Electronic journals; Periodicals; 616.15
• DOI: 10.1016/j.blre.2016.03.001
• Languages: English
• ISSNs: 0268-960X

Abstract

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.