Barka T, Henderson S, van der Noen H M
Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, NY 10029, USA.
Tumour Biol. 2000 May-Jun;21(3):145-52. doi: 10.1159/000030121.
The objective of our study was to test if a tumor expressing a transgene coding for a membrane-bound protein is amenable to immunotherapy by antibodies to the same protein. To this end, we have established an Ehrlich ascites tumor (EAT) cell line, EAT-DAP, stably expressing human, membrane-bound placental alkaline phosphatase (PLAP) by infecting EAT cells (EATC) with the retroviral vector DAP and selecting neomycin-resistant cells. EATC and EAT-DAP cells grew at similar rates in vitro, and produced ascites tumor in Swiss-Webster mice with similar efficiency. We have treated mice bearing EAT-DAP ascites tumor with a mouse monoclonal antibody to human PLAP or with a monoclonal antibody to human C proteins of the heterogenous ribonucleoprotein complex (hnRNP). The average survival of mice treated with anti-hnRNP was 16.4 +/- 1.1 days (n = 8). Treatment with anti-PLAP prolonged the survival of mice; in 4 mice average survival was 23.3 +/- 5.7 days. Four animals, however, survived for 60 days when they were killed and had no visible signs of tumor. These data support the notion that passive immunotherapy using antibodies against a membrane protein, expressed in tumor cells transduced by a viral vector coding for that protein, may be effective in controlling tumor growth.
我们研究的目的是测试表达编码膜结合蛋白的转基因的肿瘤是否适合通过针对同一蛋白的抗体进行免疫治疗。为此,我们建立了一种艾氏腹水瘤(EAT)细胞系,即EAT-DAP,通过用逆转录病毒载体DAP感染EAT细胞(EATC)并筛选新霉素抗性细胞,使其稳定表达人膜结合胎盘碱性磷酸酶(PLAP)。EATC和EAT-DAP细胞在体外以相似的速率生长,并以相似的效率在瑞士-韦伯斯特小鼠中产生腹水瘤。我们用抗人PLAP的小鼠单克隆抗体或抗异质核糖核蛋白复合物(hnRNP)的人C蛋白的单克隆抗体治疗携带EAT-DAP腹水瘤的小鼠。用抗hnRNP治疗的小鼠的平均存活时间为16.4±1.1天(n = 8)。用抗PLAP治疗可延长小鼠的存活时间;4只小鼠的平均存活时间为23.3±5.7天。然而,有4只动物在被处死时存活了60天,且没有明显的肿瘤迹象。这些数据支持这样一种观点,即使用针对膜蛋白的抗体进行被动免疫治疗,该膜蛋白在由编码该蛋白的病毒载体转导的肿瘤细胞中表达,可能对控制肿瘤生长有效。