2005 Fiscal Year Final Research Report Summary
Development of molecular targeting therapy for head and neck cancer by targeting membrane type MMP and EBV antigen
| Project/Area Number |
15390514
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kanazawa University |
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Principal Investigator |
YOSHIZAKI Tomokazu Kanazawa University, Hospital, Assistant professor, 医学部附属病院, 講師 (70262582)
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| Co-Investigator(Kenkyū-buntansha) |
MURONO Shigeyuki Kanazawa University, Graduate School of Medicine, Instructor, 大学院・医学系研究科, 助手 (20345622)
FURUKAWA Mitsuru Kanazawa University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40092803)
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| Project Period (FY) |
2003 – 2005
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| Keywords | EB virus / MT1MMP / antibody / LMP1 / MMP inhibitor |
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| Research Abstract |
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.
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