供者淋巴细胞输注研究在白血病治疗中的进展

The latest advances of research on donor lymphocyte infusion in treatment of leukemia

由供者T细胞介导的同种异体反应性,可在异基因移植后产生持久的免疫控制,或消除微小残留病。作为过继免疫治疗的重要方法,近年来随着研究的深入,我们对供者淋巴细胞输注(donor lymphocyte infusion,DLI)效应机制有了新的认识。现在,DLI的研究主要集中在:增强移植物抗白血病(GVL)效应以及促进特异性免疫调节反应,抑制GVHD而不削弱GVL效应。例如:输注调节T细胞、预防性地进行CD8+细胞的去除、采用肿瘤特异的或mHA特异的CTL进行过继免疫治疗。DLI的修饰,如过继转移抗原特异性T细胞,转导自杀基因入供者淋巴细胞等,以及应用高敏感、定量RT-PCR技术加强DLI后分子水平监测,使得DLI临床疗效显著提高。

Alloreactivity mediated by donor T cells can produce durable immunologic control or eradication of residual malignancy after allo-transplantation. Along with thorough research,we have learned more about the effective mechanisms of donor lymphocyte infusion（DLI） as a significant method of adoptive immunotherapy. Current research on DLI is focused on augmentation of the graft versus leukemia （GVL） effect as well as promoting specific immunoregualtory responses which suppress GVHD without impairing GVL,including infusion of regulatory T cells, prophylactic transfer of CD8-depleted do- nor lymphocyte,adoptive immunotherapy with tumor-specific or mHA-specific cytotoxic T lympbocytes. Modified DL/ in- cludes adoptive transfer of antigen-specific T cell population, transfer of suicide genes into donor lymphocytes etc, and em- phasis on monitoring of the molecular level by highly sensitive quantitative real-time PCR after DLI to enhance the clinical curative effect significantly.