内容紹介
Novel Therapeutic Strategy for Human Epidermal Growth Factor Receptor 2-Positive Gastric Cancer
Summary
Trastuzumab(Tmab), a humanized monoclonal antibody that selectively targets human epidermal growth factor receptor 2(HER2), is currently used in the clinical setting for the treatment of both breast and gastric cancer. While Tmab has shown improvements in patient prognoses, acquired resistance to this agent remains an issue. While some novel HER2-targeted agents have been approved for clinical use in breast cancer, no such agent has shown treatment efficacy for gastric malignancies with Tmab-resistance. Nanotechnology, which has progressed rapidly, has been applied to medical fields in recent years. Gold nanoparticles, which are characterized by their in vivo stability and ease of surface modification, have been reported to show efficacy as the carriers of therapeutic agents, such as drugs, antibodies, peptides, and nucleic acids. In this work, we developed Tmab-conjugated gold nanoparticles and demonstrate their efficacy for the treatment of HER2-positive, Tmab-resistant gastric cancer cell lines. Our findings demonstrate that Tmab-conjugated gold nanoparticles have the potential to be a novel HER2-targeted therapeutic agent.
要旨
trastuzumab(Tmab)は,human epidermal growth factor receptor 2(HER2)に対するヒト化モノクローナル抗体で,現在乳癌や胃癌に対して臨床使用されており予後の改善に寄与しているが,一方でHER2の低発現(約20%)やTmab抵抗性などの問題も存在している。Tmab抵抗性癌に対する新たなHER2標的製剤が開発されているが,乳癌とは異なり胃癌に対しては臨床的に有効性が証明されたものは未だなく,新たな治療薬の開発が望まれている。ナノ技術は,近年その発展に伴い医療へも応用されてきている。金ナノ粒子は,生体内での安定性と表面修飾の容易性などの特性があり,抗体やペプチド,核酸医薬などの薬物送達においてその有用性が報告されている。今回われわれは,Tmabを搭載した金ナノ粒子製剤を開発し,Tmabに抵抗性を示すHER2陽性胃癌細胞株に対する有意な治療効果を確認した。Tmab搭載金ナノ粒子は新たなHER2標的製剤になり得ると考えている。
目次
Summary
Trastuzumab(Tmab), a humanized monoclonal antibody that selectively targets human epidermal growth factor receptor 2(HER2), is currently used in the clinical setting for the treatment of both breast and gastric cancer. While Tmab has shown improvements in patient prognoses, acquired resistance to this agent remains an issue. While some novel HER2-targeted agents have been approved for clinical use in breast cancer, no such agent has shown treatment efficacy for gastric malignancies with Tmab-resistance. Nanotechnology, which has progressed rapidly, has been applied to medical fields in recent years. Gold nanoparticles, which are characterized by their in vivo stability and ease of surface modification, have been reported to show efficacy as the carriers of therapeutic agents, such as drugs, antibodies, peptides, and nucleic acids. In this work, we developed Tmab-conjugated gold nanoparticles and demonstrate their efficacy for the treatment of HER2-positive, Tmab-resistant gastric cancer cell lines. Our findings demonstrate that Tmab-conjugated gold nanoparticles have the potential to be a novel HER2-targeted therapeutic agent.
要旨
trastuzumab(Tmab)は,human epidermal growth factor receptor 2(HER2)に対するヒト化モノクローナル抗体で,現在乳癌や胃癌に対して臨床使用されており予後の改善に寄与しているが,一方でHER2の低発現(約20%)やTmab抵抗性などの問題も存在している。Tmab抵抗性癌に対する新たなHER2標的製剤が開発されているが,乳癌とは異なり胃癌に対しては臨床的に有効性が証明されたものは未だなく,新たな治療薬の開発が望まれている。ナノ技術は,近年その発展に伴い医療へも応用されてきている。金ナノ粒子は,生体内での安定性と表面修飾の容易性などの特性があり,抗体やペプチド,核酸医薬などの薬物送達においてその有用性が報告されている。今回われわれは,Tmabを搭載した金ナノ粒子製剤を開発し,Tmabに抵抗性を示すHER2陽性胃癌細胞株に対する有意な治療効果を確認した。Tmab搭載金ナノ粒子は新たなHER2標的製剤になり得ると考えている。