人卵巢癌肾癌排斥抗原基因、抗原肽及其免疫学特性研究

The model of xenografted human ovarian carcinoma in SCID mice and its homologous cell lines and ovarian-carcinoma-specific CTL lines were established. The expression of three MAGE family genes in human ovarian cancer cells was detected by RT-PCR. We investigated the relationship of expression of MHC molecules and immune-related genes (TAP, LMP and CIITA) in human ovarian cancer cells through IFN-gamma induction. Based on those data, analysis of immunobiology feature of human ovary cancer cells prepared for providing experimental basic how to raise tumor antigenicity and enhance human body anti-tumor capability. We successfully cloned HLA-A2 gene and it expressed on COS-7 cells. Construction and identification of cDNA library of human ovary carcinoma were screening by used SEREX technique, and discovery of new tumor specific antigenic genes and its expressed proteins were used by a series of immunochemistry methods. Analysis of localization of protein in cell and tumor expressed spectrum through Northern blot, Western blot and RT-PCR methods. Our initial observation suggest that relatively large numbers of patients with solid tumor to develop specific immunity to this expressed-protein (tumor antigen), which anti-expressed-protein antibody in patient serums were detected by ELISA method. And further application of HLA-A2 restricted TIL recognized specific tumor antigenic peptides by killing test, the results showed they may provide a target for immunotherapeutic approaches as peptide vaccine in a variety of solid tumors.

肿瘤抗原在细胞被加工后以抗原肽-HLAI类分子复合物形式激活杀伤T细胞。本项目运用重组cDNA表达文库血清分析技术，寻找卵巢癌或肾癌肿瘤排斥及其编码基因，以HLA-A2分子接纳抗原肽的特定锚着基序模定肿瘤排斥免疫原，获取下抗原肽，诱导特异性抗肿瘤免疫应答，并和HLA-A2分子天然结合的肿瘤抗原肽结构作比较，为发展治疗性肽疫苗作基础。