Vidal Claudia I, Mintz Paul J, Lu Karen, Ellis Lee M, Manenti Luigi, Giavazzi Raffaella, Gershenson David M, Broaddus Russell, Liu Jinsong, Arap Wadih, Pasqualini Renata
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Oncogene. 2004 Nov 25;23(55):8859-67. doi: 10.1038/sj.onc.1208082.
To gain insight into the mechanisms of molecular recognition and humoral immune response in ovarian cancer, we used fingerprinting, a phage display-based combinatorial selection to isolate peptide ligands to tumor-related antibodies present in ascites from patients with advanced disease. First, we have isolated a consensus motif (sequence CVPELGHEC) in 86% of the peptides screened; this enriched motif was selected from a total of 10(8)-10(9) unique random sequences present in the library. Next, we identified the heat-shock protein 90 kDa (HSP90) as the native antigen mimicked by the motif. Finally, we evaluated the expression of HSP90 and the presence of antibodies against the HSP90-mimic peptide in a large panel of ovarian cancer patients and controls. In tissue microarrays, we show that the expression of HSP90 is ubiquitous. However, the corresponding humoral immune response against HSP90 is restricted to a subset of patients with stage IV disease. Together, these results show that screening humoral response can identify tumor antigens that may serve as molecular targets in ovarian cancer. Recognition of such relevant proteins in the immunobiology of malignant tumors may lead to the development of therapies
为深入了解卵巢癌中分子识别和体液免疫反应的机制，我们采用了指纹图谱技术，这是一种基于噬菌体展示的组合筛选方法，用于从晚期疾病患者腹水中存在的肿瘤相关抗体中分离肽配体。首先，我们在筛选的86%的肽中分离出一个共有基序（序列CVPELGHEC）；这个富集的基序是从文库中总共10(8)-10(9)个独特的随机序列中筛选出来的。接下来，我们确定热休克蛋白90 kDa（HSP90）是该基序模拟的天然抗原。最后，我们在大量卵巢癌患者和对照中评估了HSP90的表达以及针对HSP90模拟肽的抗体的存在情况。在组织微阵列中，我们发现HSP90的表达普遍存在。然而，针对HSP90的相应体液免疫反应仅限于IV期疾病患者的一个亚组。总之，这些结果表明，筛选体液反应可以识别可能作为卵巢癌分子靶点的肿瘤抗原。在恶性肿瘤免疫生物学中识别此类相关蛋白可能会导致治疗方法的发展。
