Sahin U, Türeci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M
Medizinische Klinik und Poliklinik, Innere Medizin I, University of Saarland Medical School, Homburg, Germany.
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11810-3. doi: 10.1073/pnas.92.25.11810.
Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.
将来自人类黑色素瘤、肾癌、星形细胞瘤和霍奇金病的cDNA文库在大肠杆菌中表达,并筛选与自体患者血清中高效价IgG抗体反应的克隆,从而发现每种肿瘤中至少有四种具有受限表达模式的抗原。除了已知能引发T细胞反应的抗原,如MAGE-1和酪氨酸酶外,还鉴定出许多在同一类型肿瘤中过度表达或特异性表达的其他抗原。序列分析表明,这些分子中的许多除了是特异性免疫反应的靶点外,可能还与肿瘤生长有关。针对特定抗原的抗体通常局限于患有相同肿瘤类型的患者。通过自体肿瘤cDNA表达克隆的血清学分析能够在分子水平上轻易定义的人类肿瘤抗原的意外频率,表明人类肿瘤在自体宿主中引发多种特异性免疫反应,并为人类癌症提供了诊断和治疗方法。