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

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• 作者：Giuseppina Li Pira^a ; ^b ; ^{giuseppina.lipira@opbg.net" class="auth_mail" title="E-mail the corresponding author} ; Stefano Di Cecca^a ; ^{stefano.dicecca@opbg.net" class="auth_mail" title="E-mail the corresponding author} ; Mauro Montanari^a ; ^b ; ^{mauro.montanari@opbg.net" class="auth_mail" title="E-mail the corresponding author} ; Lorenzo Moretta^c ; ^{lorenzo.moretta@opbg.net" class="auth_mail" title="E-mail the corresponding author} ; Fabrizio Manca^c ; ^{fabrizio.manca@opbg.net" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hemopoietic stem cell transplantation ; Graft-versus-host disease ; Alloreactive T-cells ; T-cell activation ; Allodepletion ; Cell manipulation
• 刊名：Blood Reviews
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：30
• 期：4
• 页码：297-307
• 全文大小：796 K

文摘

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.