Lim S H, Coleman S
Department of Haematology, University of Wales College of Medicine, Cardiff, UK.
Am J Hematol. 1997 Jan;54(1):61-7. doi: 10.1002/(sici)1096-8652(199701)54:1<61::aid-ajh9>3.0.co;2-2.
Various clinical observations have implicated T cells in the control of chronic myeloid leukemia (CML). These observations have in recent years been supported by laboratory results indicating the presence of CML-specific T cells in the lymphocyte repertoire of both normal healthy individuals and disease-bearing patients. Both MHC-unrestricted and MHC-restricted immune effector mechanisms are involved. Donor lymphocyte infusion has produced encouraging GvL effects. However, future adoptive immunotherapy may depend on the isolation and generation of leukemia-specific T cells. Although many proteins may potentially act as leukemia antigens in CML for MHC-restricted cytotoxicity, the bcr-abl fusion protein has been most extensively investigated. There is now much evidence to suggest that the bcr-abl junctional peptides are capable of eliciting both CD4 and CD8 responses in normal healthy donors and CML patients. Furthermore, the T-cell lines generated react with autologous or HLA-matched fresh CML cells, suggesting that the bcr-abl fusion protein can be processed in vivo so that the joining segment is bound to HLA molecules in a configuration and concentration similar to those of the immunizing peptide for antigen recognition by the antigen-specific T-cell receptor. These results also indicate that the bcr-abl junctional peptides may be used for immunotherapy of CML. Other strategies available for immunotherapy of CML include immunologically or genetically manipulated donor T-cell infusion, the use of cytokines, adoptive immunotherapy with leukemia-reactive T-cells expanded ex vivo, and immune gene therapy. Novel and rational immunotherapy may therefore play an important adjuvant role in future in the management of patients with CML.
多项临床观察表明，T细胞参与慢性髓性白血病（CML）的控制。近年来，这些观察结果得到了实验室结果的支持，这些结果表明，在正常健康个体和患病患者的淋巴细胞库中都存在CML特异性T细胞。MHC非限制性和MHC限制性免疫效应机制均参与其中。供体淋巴细胞输注产生了令人鼓舞的移植物抗白血病（GvL）效应。然而，未来的过继性免疫疗法可能依赖于白血病特异性T细胞的分离和产生。尽管许多蛋白质可能潜在地作为CML中MHC限制性细胞毒性的白血病抗原，但bcr-abl融合蛋白已得到最广泛的研究。现在有许多证据表明，bcr-abl连接肽能够在正常健康供体和CML患者中引发CD4和CD8反应。此外，所产生的T细胞系与自体或HLA匹配的新鲜CML细胞发生反应，这表明bcr-abl融合蛋白可以在体内进行加工，使得连接片段以与免疫肽相似的构型和浓度与HLA分子结合，以供抗原特异性T细胞受体进行抗原识别。这些结果还表明，bcr-abl连接肽可用于CML的免疫治疗。CML免疫治疗的其他可用策略包括免疫或基因操纵的供体T细胞输注、细胞因子的使用、过继性免疫疗法，即使用体外扩增的白血病反应性T细胞，以及免疫基因治疗。因此，新型合理的免疫疗法未来可能在CML患者的管理中发挥重要的辅助作用。
