2013 Fiscal Year Final Research Report
Development of molecular targeting therapy using nuclear-transpoted humanized monoclonal antibody
| Project/Area Number |
25670195
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Keio University |
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Principal Investigator |
YAMADA Taketo 慶應義塾大学, 医学部, 准教授 (60230463)
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| Research Collaborator |
HAYASHI Mutsumi 慶應義塾大学, 医学部, 特任助教 (60327575)
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| Project Period (FY) |
2013-04-01 – 2014-03-31
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| Keywords | 癌 / トランスレーショナルリサーチ / 病理学 / 分子標的療法 |
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| Research Abstract |
CD26 is on cell surface of various types of cancers. It was shown humanized anti-CD26 monoclonal antibody(Ab) inhibited cancer cell growth and the Ab treatment induced nuclear translocation of both CD26 and YS110. In response to Ab treatment, it was revealed nuclear CD26 interacted with a genomic flanking region of POLR2A gene, a subunit of RNA polymerase II, using a chromatin immunoprecipitation assay. This interaction with nuclear CD26 and POLR2A gene consequently led to transcriptional repression of the POLR2A gene, resulting in retarded cell proliferation of cancer cells. Anti-cancer reagent X was conjugated with Ab, as a result X-Ab inhibited severely cancer cell growth as compaired with Ab only. It was revealed that Ab or X-Ab did not impair cell growth of normal human endothelial cell and T lymphocyte with CD26 expression. Xenografted human carcinomas were reduced significantly by X-Ab treatment as compared with Ab treatment.
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