Montagna D, Maccario R, Locatelli F
Department of Pediatrics, Laboratory of Immunology, University of Pavia, Italy.
Int J Immunogenet. 2008 Aug;35(4-5):389-93. doi: 10.1111/j.1744-313X.2008.00797.x.
Recurrence of the original disease remains the main cause of treatment failure in patients given allogeneic haematopoietic stem cell transplantation for either acute or chronic leukaemia. Infusion of donor lymphocytes (DLI) is useful for rescuing patients with chronic myeloid leukaemia, while this option is of limited value in patients with acute leukaemia. Moreover, DLI may cause fatal graft-versus-host disease (GvHD) or prolonged myelosuppression. A more sophisticated approach is that of generating and expanding ex vivo T-cell lines or clones able to selectively or preferentially lyse leukaemia blasts, while sparing non neoplastic targets. In this review, we will summarize the results we have obtained in vitro utilizing an approach based on the generation of leukaemia reactive cytotoxic T-lymphocytes through the use of apoptotic leukaemia cells as source of tumor antigens. Our approach proved to be feasible and effective in the experimental model for different types of leukaemia, even when the donor was HLA-disparate with the recipient. This strategy has to be tested in the clinical setting for proving its efficacy in preventing/treating leukaemia recurrence.
对于接受异基因造血干细胞移植治疗急性或慢性白血病的患者,原发病复发仍是治疗失败的主要原因。输注供体淋巴细胞(DLI)对挽救慢性髓性白血病患者有用,而这一选择对急性白血病患者价值有限。此外,DLI可能会导致致命的移植物抗宿主病(GvHD)或长期骨髓抑制。一种更复杂的方法是在体外生成并扩增能够选择性或优先裂解白血病母细胞,同时不损伤非肿瘤性靶细胞的T细胞系或克隆。在本综述中,我们将总结我们通过使用凋亡白血病细胞作为肿瘤抗原来源,基于生成白血病反应性细胞毒性T淋巴细胞的方法在体外获得的结果。我们的方法在不同类型白血病的实验模型中被证明是可行且有效的,即使供体与受体的人类白细胞抗原(HLA)不匹配。该策略必须在临床环境中进行测试,以证明其在预防/治疗白血病复发方面的疗效。