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Development of Tumor-Specific Immunotherapy for Bone and Soft-Tissue Sarcomas

骨和软组织肉瘤肿瘤特异性免疫疗法的发展

基本信息

批准号：
16390439
负责人：
UEDA Takafumi
金额：
$ 6.8万
依托单位：
独立行政法人国立病院機構(大阪医療センター臨床研究部) (2006-2007)Osaka University (2004-2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390439/
关键词：
malignant bone & soft-tissue tumor sarcomas tumor-specific immnotherapy WT1 gene SSX gene DC vaccine therapy

项目摘要

To develop tumor-specific immunotherapy for bone and soft-tissue sarcomas, we have planned and conducted translational and clinical researches as follows ; 1) We analyzed the overexpression of WT1 gene and its correlation with prognosis in 52 patients with soft-tissue sarcoma, elucidating WT1 overexpression being as a prognostic factor for patiets with soft-tissue sarcoma and WT1 peptide to be a candidate of molecular targets for tumor-specific immunotherapy for sarcomas(Cancer 106(10) : 2233-2240, 2006) . 2) We have started a phase I/II clinical trial of tumor-specific immunotherapy using WT1 peptide for a variety of solid cansers including bone and soft-tissue sarcomas(30 cases) from April 2004, to evaluate the efficacy and toxicity of WT1 peptide. Twenty cases of locally advanced and/or metastatic bone and soft-tissue sarcomas were enrolled to the trial until March 2008. There are 8 SD(stable disease) , 11PD(progressive disease) , and one suspended case by patient's decision, without PR(partial response) /or CR(complete response) cases. We have not yet experienced severe toxicity in WT1 vaccinations except for local redness/swelling of intracutaneous injection sites. 3) We have performed an experimental DC(denritic cell) immunotherapy using C3H murine model of lung metastases from osteosarcoma(LM8) , which was originally established in our laboratory, and demonstrated the anti-tumor activity of DC vaccine immunotherapy for primary tumors and lung metastases of LM8 osteosarcoma cells(Clin Orthop 453 : 318-327, 2006).For further projects, we will progress the phase I/II clinical trial of tumor-specific immunotherapy using WT1 peptide for bone and soft-tissue sarcomas(30 cases) , and also develop a new molecular targeting therapy for bone and soft-tissue sarcomas focusing SSX gene products as a cancer-testis antigen frequently expressed not only in sarcomas but also in a variety of solid cancers.

为了开发骨和软组织肉瘤的肿瘤特异性免疫治疗，我们计划并开展了以下转化和临床研究：1）分析52例软组织肉瘤中WT 1基因的过表达及其与预后的关系，阐明WT 1过表达是软组织肉瘤患者的预后因素，WT 1肽是肿瘤治疗的候选分子靶点。肉瘤的特异性免疫疗法（Cancer 106（10）：2233-2240，2006）。2)我们从2004年4月开始了一项使用WT 1肽的肿瘤特异性免疫治疗的I/II期临床试验，用于各种实体癌，包括骨和软组织肉瘤（30例），以评估WT 1肽的疗效和毒性。截至2008年3月，该试验入组了20例局部晚期和/或转移性骨和软组织肉瘤病例。有8例SD（疾病稳定）、11例PD（疾病进展）和1例患者决定暂停的病例，无PR（部分缓解）/CR（完全缓解）病例。除了皮内注射部位的局部发红/肿胀外，我们尚未在WT 1疫苗接种中发生严重毒性。3)我们进行了实验性DC本研究使用本实验室最初建立的骨肉瘤肺转移（LM 8）的C3 H小鼠模型，对DC（树突状细胞）免疫疗法进行了研究，并证明了DC疫苗免疫疗法对LM 8骨肉瘤细胞的原发性肿瘤和肺转移的抗肿瘤活性（临床骨科453：318-327，2006）。对于进一步的项目，我们将推进使用WT 1肽的肿瘤特异性免疫疗法用于骨和软组织肉瘤的I/II期临床试验（30例），并开发一种新的分子靶向治疗骨和软组织肉瘤聚焦SSX基因产物作为癌症睾丸抗原频繁表达不仅在肉瘤，而且在各种实体癌。