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KAKEN_24590490seika.pdf
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:415.5 KB
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:Apr 11, 2016 |
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ADAM28の分子作用機構解明と分子標的治療薬開発の基礎研究
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ADAM28 ノ ブンシ サヨウ キコウ カイメイ ト ブンシ ヒョウテキ チリョウヤク カイハツ ノ キソ ケンキュウ
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ADAM28 no bunshi sayo kiko kaimei to bunshi hyoteki chiryoyaku kaihatsu no kiso kenkyu
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Research and development of human neutralizing antibodies aiming at treatment of non-small cell lung carcinoma
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望月, 早月
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モチヅキ, サツキ
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Mochizuki, Satsuki
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慶應義塾大学・医学部・講師
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Research team head
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科研費研究者番号 : 80365428
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岡田, 保典
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オカダ, ヤスノリ
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Okada, Yasunori
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慶應義塾大学・医学部・教授
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Research team member
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科研費研究者番号 : 00115221
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2015
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科学研究費補助金研究成果報告書
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2014
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ADAM28(a disintegrin and metalloproteinase 28)は癌細胞の増殖・転移に重要な役割を果たしている。本研究では, 肺癌治療を目指してヒト型抗ADAM28抗体(211-14)を開発した。211-14抗体は, ADAM28高発現ヒト肺腺癌細胞株(PC-9)の細胞増殖を濃度依存的に抑制した。また, PC-9 ffLuc-cp156細胞をマウスの尾静脈内注入3週後に抗体治療を開始した実験では, 肺内腫瘍増殖と全身転移の有意な遅延がみられ, 平均生存期間も11週延長した。ヒト型抗ADAM28抗体211-14は, ヒト肺癌の分子標的治療薬剤として応用できる可能性が期待される。
ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, plays an important role in cancer cell proliferation and metastasis. In the present study, we screened Human Combinatorial Antibody Library by phage display panning and obtained antibodies (211-14 and 211-12) against ADAM28. Tumor growth and metastasis of the lung tumors after intravenous injection of PC-9 ffLuc-cp156 lung carcinoma cells were significantly inhibited by the antibody treatment, improving survival rate of the mice. These data indicate that our antibodies 211-14 and 211-12 neutralize ADAM28 activity and antibody 211-14 inhibits cancer cell proliferation and metastasis in vivo. The antibodies could be used as an ADAM28 inhibitor for clinical application to treat the patients with lung or breast carcinoma in the future.
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研究種目 : 基盤研究(C)
研究期間 : 2012～2014
課題番号 : 24590490
研究分野 : 癌細胞増殖・転移, メタロプロテアーゼ, 細胞外マトリックス
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