Human cancer vaccines

成功研究了三个研究项目。1)从自体CTL和OS2000骨肉瘤细胞系中鉴定出人骨肉瘤抗原PBF，乳突瘤结合因子。PBF在大部分软部肿瘤以及大约50%的上皮性肿瘤中表达，而在正常组织中没有检测到，特别是在蛋白质水平上。这些观察结果表明，PBF可用于癌症的免疫治疗。2)肿瘤抗原的反向免疫途径表明survivin可作为肿瘤抗原。特别是在许多癌症患者中，生存素衍生的2Bpeptide以HLA-A24受限的方式诱导了CTL。我们目前正在对这种肽进行一期临床试验，用于结肠癌、乳腺癌和肺癌，表明没有不良反应。其中一些患者表现出某些临床反应，如CT显示肿瘤大小缩小以及肿瘤标志物水平降低。我们还在滑膜肉瘤患者中进行从SYT-SSX染色体易位融合产物中提取的hla - a24限制性B肽的I期临床试验。在这项试验中，没有不良反应，6名患者中有2名显示四聚体阳性CTL前体数量增加。3)利用计算机生物信息学方法鉴定出35种新的肿瘤抗原。采用RT-PCR分析的湿法研究证实，35种抗原中有7种作为肿瘤抗原具有严格的表达谱。

Three research projects were successfully studied. 1) We identified human osteosarcoma antigen PBF, papilloma-binding factor, from autologous CTL and osteosarcoma OS2000 line. PBF was expressed in a large part of soft part tumors as well as approximately 50 % tumors of epithelial origins, whereas it was not detected in normal part of tissues particularly in the protein level. These observations suggest that PBF could be utilized in the immunotherapy of cancers. 2) Reverse-immunological approaches of tumor antigens indicated that survivin could work as the tumor antigens. Particularly, survivin-derived 2Bpeptide induced CTL in many cancer patients in the HLA-A24 restricted manner. We are now underway the phase I clinical trials of this peptide in colon, breast, lung cancers, indicating that there are no adverse effects. Some of these patients demonstrated certain clinical responses such as reduction in tumor size in CT as well as in tumor marker levels. We are also underway the phase I clinical trials of HLA-A24-restricted B peptide derived from the SYT-SSX chromosomal translocation fusion product in synovial sarcoma patients. In this trial, there are no adverse effects, and two out of six patients indicated an increasing number of tetramer-positive CTL precursors. 3) We identified 35 novel tumor antigens by bioinformatics in silico approaches. Wet studies by using RT-PCR analysis confirmed that 7 out of 35 antigens have strict expression profiles as the tumor antigens.