Weinschenk Toni, Gouttefangeas Cécile, Schirle Markus, Obermayr Florian, Walter Steffen, Schoor Oliver, Kurek Raffael, Loeser Wolfgang, Bichler Karl-Horst, Wernet Dorothee, Stevanović Stefan, Rammensee Hans-Georg
Department of Immunology, Institute for Cell Biology, University of Tübingen, Germany.
Cancer Res. 2002 Oct 15;62(20):5818-27.
Our aim is to identify as many candidates as possible for tumor-associated T-cell epitopes in individual patients. First, we performed expression profiling of tumor and normal tissue to identify genes exclusively expressed or overexpressed in the tumor sample. Then, using mass spectrometry, we characterized up to 77 different MHC ligands from the same tumor sample. Several of the MHC ligands were derived from overexpressed gene products, one was derived from a proto-oncogene, and another was derived from a frameshift mutation. At least one was identified as an actual T-cell epitope. Thus, we could show that by combining these two analytic tools, it is possible to propose several candidates for peptide-based immunotherapy. We envision the use of this novel integrated functional genomics approach for the design of antitumor vaccines tailored to suit the needs of each patient.
我们的目标是为个体患者识别尽可能多的肿瘤相关T细胞表位候选物。首先，我们对肿瘤组织和正常组织进行表达谱分析，以识别在肿瘤样本中特异性表达或过表达的基因。然后，我们使用质谱法对来自同一肿瘤样本的多达77种不同的MHC配体进行了表征。其中几种MHC配体来自过表达的基因产物，一种来自原癌基因，另一种来自移码突变。至少有一种被鉴定为实际的T细胞表位。因此，我们可以证明，通过结合这两种分析工具，有可能提出几种基于肽的免疫治疗候选物。我们设想使用这种新型的综合功能基因组学方法来设计适合每位患者需求的抗肿瘤疫苗。
