Zhao Fei, Vermeer Benjamin, Lehmann Ulrich, Kreipe Hans, Manns Michael P, Korangy Firouzeh, Greten Tim F
Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
Immunology. 2009 Sep;128(1):134-40. doi: 10.1111/j.1365-2567.2009.03090.x.
Pancreatic cancer is the fourth leading cause of cancer related death in the United States. Despite numerous efforts in developing new therapies, the prognosis for patients with pancreatic cancer remains poor. Mouse models for spontaneous pancreatic cancer represent an ideal system to develop immunotherapeutic approaches. The aim of this study was to identify new tumour antigens in a murine model that mimics human disease closely, and to verify the results in patients with pancreatic cancer. We analysed a murine pancreatic complementary DNA expression library with serum from tumour-bearing mice, which led to the identification and isolation of several antigens. One of the antigens repeatedly identified in this screening was Tankyrase-2. Here, we show Tankyrase-2 as an antigen eliciting humoral responses not only in mice with established tumours, but also in mice with pre-malignant lesions. Finally, antibody responses to Tankyrase-2 were found in the serum of patients with pancreatic cancer. Reverse transcriptase-polymerase chain reaction analysis showed Tankyrase-2 expression in human pancreatic tumour. These findings show the relevance of spontaneous murine tumour models for the identification of human tumour antigens.
胰腺癌是美国癌症相关死亡的第四大主要原因。尽管在开发新疗法方面付出了诸多努力，但胰腺癌患者的预后仍然很差。自发性胰腺癌小鼠模型是开发免疫治疗方法的理想系统。本研究的目的是在一个与人类疾病密切相似的小鼠模型中鉴定新的肿瘤抗原，并在胰腺癌患者中验证结果。我们用荷瘤小鼠的血清分析了一个小鼠胰腺互补DNA表达文库，从而鉴定并分离出了几种抗原。在该筛选中反复鉴定出的一种抗原是端锚聚合酶-2。在此，我们表明端锚聚合酶-2作为一种抗原，不仅在患有已确立肿瘤的小鼠中，而且在患有癌前病变的小鼠中均可引发体液反应。最后，在胰腺癌患者的血清中发现了针对端锚聚合酶-2的抗体反应。逆转录酶-聚合酶链反应分析显示端锚聚合酶-2在人类胰腺肿瘤中表达。这些发现表明自发性小鼠肿瘤模型在鉴定人类肿瘤抗原方面具有相关性。
