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Development of molecular targeting therapy for head and neck cancer by targeting membrane type MMP and EBV antigen

靶向膜型MMP和EBV抗原开发头颈癌分子靶向治疗

基本信息

批准号：
15390514
负责人：
YOSHIZAKI Tomokazu
金额：
$ 6.98万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390514/
关键词：
EB virus MT1MMP antibody LMP1 MMP inhibitor MMP 頭頸部がん分子標的上咽頭がん

项目摘要

1)Cytotoxic and cytostatic effect of Anti-MT1-MMP antibody 114F1 labeled with 131I was evaluated between HEK293 cell and MT1-MMP stable transfected-HEK293. Colony, formation assay showed there was no difference between these two cells, indicating that anti-MT1MMP with 131I did not have cytostatic effect. However, additional BB94, an inhibitor of MMP, enhanced the expression of cell surface MT1-MMP, and binding affinity of antibody to cell was enhanced 10 to 20% when 100ug of antibody was administrated.2)Affinity to MT1MMP was reevaluated among,114F,113-5B7 and AB815 using flow cytometry. It showed that AB815 had 5 to 10 fold binding affinity compared with either 114F or 113-5B7. These, results suggests that molecular targeting therapy against MT1-MMP would be improved by the use of higher affinity antibodies and MMP inhibitors.3)Epstein-Barr virus primary oncogene LMP1 locates on cell membrane. Establishment of antibody to LMP1 was first designed. However, ectodomain of LMP1 was revealed to have 6to 7 amino acids, which is insufficient to raise antibody.4)Then, the strategy was switched to look for the cell surface molecule induced by LMP1. Mucin1 was found to a specific molecule induced by LMP1 and effect, of antibody against-mucin1 should be examined in the successional experiment.

1)在HEK 293细胞和MT 1-MMP稳定转染的HEK 293之间评价131 I标记的抗MT 1-MMP抗体114 F1的细胞毒性和细胞抑制作用。集落形成实验显示两种细胞间无差异，表明抗MT 1 MMP与131 I联合作用不具有细胞抑制作用。而加入MMP抑制剂BB 94后，细胞表面MT 1-MMP的表达增强，当加入100 μ g抗体时，抗体与细胞的结合亲和力提高了10 ~ 20%。2）流式细胞术检测114 F、113- 5 B7和AB 815对MT 1-MMP的亲和力。结果表明，与114 F或113- 5 B7相比，AB 815具有5至10倍的结合亲和力。结论：3）EB病毒原癌基因LMP 1定位于细胞膜上。首先设计了抗LMP 1抗体的建立。但是，LMP 1的胞外结构域只有6 ~ 7个氨基酸，不足以产生抗体。4）随后，我们将策略转移到寻找LMP 1诱导的细胞表面分子上。Mucin 1是LMP 1诱导的特异性分子，其作用效果有待于后续实验的进一步研究。