Hicks Christine, Cheung Carol, Lindeman Robert
Department of Haematology, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia.
Leuk Res. 2003 Nov;27(11):1051-61. doi: 10.1016/s0145-2126(03)00058-4.
Leukaemic blast cells lack co-stimulatory molecules such as B7, necessary for T-lymphocyte activation. We have used modified CD80+ (B7-1+) tumour cells, with autologous, IL-2 producing, stromal marrow cells in a series of subcutaneous vaccinations to provide a localised environment for the enhancement of cytotoxic T-lymphocytes (CTL) in a patient with acute myeloid leukaemia (AML). Localised inflammation was evident after the fifth and sixth injections with a reduction in the number of circulating blasts in the following 2 weeks. Peripheral blood in vitro CTL activity increased 36-47% after five injections.CD4 T-lymphocytes (5.7%) expanded from post-injection skin biopsies, expressed intracellular IFNgamma and perforin when exposed to autologous B7-1+ blasts and when co-cultured with either B7-1+ or unmanipulated autologous blast cells showed proliferative responses. In this patient, co-injection of B7-1+ tumour cells, together with a local source of sustained IL-2, resulted in an autologous anti-leukaemic in vitro immune response.
白血病原始细胞缺乏T淋巴细胞激活所必需的共刺激分子，如B7。我们使用了经修饰的CD80+(B7-1+)肿瘤细胞，与能产生白细胞介素-2的自体基质骨髓细胞一起进行了一系列皮下接种，为一名急性髓系白血病（AML）患者增强细胞毒性T淋巴细胞（CTL）提供局部环境。在第五次和第六次注射后出现局部炎症，随后两周循环原始细胞数量减少。五次注射后，外周血体外CTL活性增加36%-47%。从注射后皮肤活检中扩增出的CD4 T淋巴细胞（5.7%），在暴露于自体B7-1+原始细胞时表达细胞内干扰素γ和穿孔素，并且在与B7-1+或未处理的自体原始细胞共培养时表现出增殖反应。在该患者中，联合注射B7-1+肿瘤细胞以及局部持续来源的白细胞介素-2，导致了自体抗白血病体外免疫反应。
