Lücking-Famira K M, Daniel P T, Möller P, Krammer P H, Debatin K M
Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center.
Leukemia. 1994 Nov;8(11):1825-33.
The monoclonal antibody anti-APO-1 induces apoptosis upon triggering the cell surface molecule APO-1 (CD95), a novel member of the tumor necrosis factor/nerve growth factor receptor superfamily. We tested the efficacy of APO-1 mediated apoptosis in a model system of human leukemia in SCID mice. T-ALL cells recovered from SCID mice were sensitive towards anti-APO-1 mediated apoptosis when tested in vitro. In vivo, treatment of leukemia-bearing SCID mice with anti-APO-1 induced programmed cell death in a substantial fraction of T-ALL cells, thus leading to significantly prolonged survival. Anti-APO-1 treatment, however, failed to completely eliminate all leukemic cells. This may be due to resistance towards anti-APO-1 mediated apoptosis in a fraction of T-ALL cells. Thus, identification of cellular programs which determine sensitivity and resistance towards apoptosis may provide new perspectives for rational therapeutic interventions.
单克隆抗体抗APO-1在触发细胞表面分子APO-1（CD95）时可诱导细胞凋亡，APO-1是肿瘤坏死因子/神经生长因子受体超家族的一个新成员。我们在SCID小鼠的人白血病模型系统中测试了APO-1介导的细胞凋亡的功效。从SCID小鼠中回收的T-ALL细胞在体外测试时对抗APO-1介导的细胞凋亡敏感。在体内，用抗APO-1治疗荷白血病SCID小鼠可在相当一部分T-ALL细胞中诱导程序性细胞死亡，从而显著延长生存期。然而，抗APO-1治疗未能完全消除所有白血病细胞。这可能是由于一部分T-ALL细胞对抗APO-1介导的细胞凋亡具有抗性。因此，确定决定细胞对凋亡敏感性和抗性的细胞程序可能为合理的治疗干预提供新的视角。
