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Development of new methods in diagnosis and treatment of tumors by the targeting of chimeric protein

开发靶向嵌合蛋白的肿瘤诊断和治疗新方法

基本信息

批准号：
08557018
负责人：
MORI Shigeo
金额：
$ 9.92万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557018/
关键词：
malignant lymphoma BCL6 gene chromosomal translocation mRNA chimeric protein リンパ腫染色体 p80NPM ALK キメラ蛋白質未分化大細胞型リンパ腫 ALK遺伝子 TLS CHOP遺伝子 bcl6遺伝子

项目摘要

The chimeric gene is a unique non-natural gene made by the fusion of two different genes, causing production of a novel protein with the head and tail parts made of two different genes. Some of such chimeric protein cause specific diseases like soft part sarcoma and malignant lymphomas. This study was aimed (1)to identify new pathogenetic chimeric genes/proteins, (2)Biological function of chimeric proteins, (3)Application of chimeric proteins in the diagnosis and treatment of human diseases.(1) Identification of new pathogenetic chimeric genes/proteins :Over 20 chimeric genes were identified from human malignant lymphomas a part of which was derived from BCL6 gene. Some of them were found to be new genes. Also, a new type of TLS/FUS-CHOP chimeric gene was identified from human liposarcoma tissues.(2) Biological function of chimeric proteins :A part of the biological functions of NPM/ALK chimeric protein was clarified. Also, the biological function of BCL6 gene product was partly clarified.(3) Application of chimeric proteins in the diagnosis and treatment of human diseases :With the introduction of newly developed antibody to NPM/ALK chimeric protein, we invested an easy and conclusive diagnostic method for the NPM/ALK chimera-related human diseases. Also, we could transfer over 20 cases of human malignant lymphomas bearing different types of chimera genes. This cell line is now under study for the targeting of these genes in immunotherapy.

嵌合基因是一种独特的非自然基因，由两种不同的基因融合而成，产生一种新的蛋白质，头部和尾部由两种不同的基因组成。一些这样的嵌合蛋白引起特殊疾病，如软组织肉瘤和恶性淋巴瘤。本研究旨在(1)鉴定新的致病嵌合基因/蛋白；(2)嵌合蛋白的生物学功能；(3)嵌合蛋白在人类疾病诊断和治疗中的应用。(1)新的致病嵌合基因/蛋白的鉴定：从人恶性淋巴瘤中鉴定出20多个嵌合基因，其中部分嵌合基因来源于BCL6基因。其中一些被发现是新的基因。同时，从人脂肪肉瘤组织中鉴定出一种新的TLS/FUS-CHOP嵌合基因。(2)嵌合蛋白的生物学功能：阐明了NPM/ALK嵌合蛋白的部分生物学功能。BCL6基因产物的生物学功能也得到了部分阐明。(3)嵌合蛋白在人类疾病诊断和治疗中的应用：随着新开发的NPM/ALK嵌合蛋白抗体的引入，我们为NPM/ALK嵌合蛋白相关的人类疾病的诊断提供了一种简便、结论性的方法。此外，我们还可以移植20多例携带不同类型嵌合体基因的人类恶性淋巴瘤。该细胞系目前正在研究这些基因在免疫治疗中的靶向作用。