Development of a feline TNF-α monoclonal antibody with therapeutic potential against feline infectious peritonitis

开发具有治疗猫传染性腹膜炎潜力的猫TNF-α单克隆抗体

• 批准号: 22780285
• 负责人: TAKANO Tomomi
• 金额: $ 2万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22780285/
• 关键词: TNF-a; コロナウイルス; 抗体療法; 猫伝染性腹膜炎; 治療; TNF-α

Feline infectious peritonitis virus (FIP virus: FIPV), a feline coronavirus (FCoV) of the family Coronaviridae, causes a fatal disease called FIP in wild and domestic cat species. We previously showed that virus replication in macrophages induced TNF-α production, and that the TNF-a produced was involved in aggravating the pathology of FIP: TNF-a produced by FIPV-infected macrophages was involved in lymphopenia and an increase in the level of the cellular receptor of type II FIPV, aminopeptidase N (APN). TNF-a reportedly inhibits neutrophil apoptosis, which suggestsits involvement in neutrophilia in cats with FIP. These findings suggest that FIP symptoms may also be alleviated by administering a feline TNF-a-neutralizing antibody to cats with FIP. However, no feline TNF-a-neutralizing antibody has been developed. We attempted to prepare feline TNF-a-recognizing monoclonal antibodies (anti-feline TNF-a MAbs) and investigated whether these MAbs inhibited feline TNF-a activities. Furthermore, we investigated the application of an anti-feline TNF-a MAb as a therapeutic drug for FIP in vitro. Anti-feline TNF-a MAb 2-4 (MAb 2-4) exhibited high neutralizing activity against natural TNF-a derived from FIPV-infected macrophages, and was confirmed to inhibit the following feline TNF-a-induced conditions in vitro. It was suggested that Mab 2-4 inhibited FIP pathology by neutralizing the physiological activities of TNF-a.

猫传染性腹膜炎病毒（FIP病毒：FIPV），一种冠状科ILD和家用猫。 -FIPV感染的巨噬细胞所产生的A淋巴细胞减少症，据报道，II型FIPV氨基肽酶N（APN）的细胞受体水平增加了。通过可管理的猫tnf-a-tnf-a-fip抗体中和抗体的猫抗体。 ）这些mAb是否抑制了猫tnf-a的活性，我们研究了抗feline TNF-A mAb作为治疗药物的应用。从FIPV感染的巨噬细胞中对天然TNF-A D的高中和活性，并在体外确认抑制了猫咪TNF-A诱导的条件后，它可以通过中和TNF-A的tnf-a和tnf-a抑制。 。

项目成果

猫伝染性腹膜炎の病態悪化機構の解明

阐明猫传染性腹膜炎的恶化机制

• 发表时间: 2010
• 作者: 高野友美; 宝達勉
• 通讯作者: 宝達勉

猫伝染性腹膜炎（FIP）治療薬としてのクロロキンの有効性について

关于氯喹治疗猫传染性腹膜炎（FIP）的有效性

• 发表时间: 2012
• 作者: 山本崇史;城取宏治;三浦綾乃;大島毅;佐久間悠;橘裕之;上田俊平;藤本鉄兵;森香澄;和田成一;柿崎竹彦;伊藤伸彦;高野友美
• 通讯作者: 高野友美

高野友美、大山拓、黒元愛子、佐藤亮一、宝達勉

高野友美、大山拓、黑本爱子、佐藤良一、保达勉

• 发表时间: 2010
• 作者: 高野友美;大山拓;黒元愛子;佐藤亮一;宝達勉
• 通讯作者: 宝達勉

猫伝染性腹膜炎ウイルス(FIPV)感染マクロファージから放出される TNF-aは好中球エラスターゼの産生を促進する、第151回日本獣医学会学術集会

猫传染性腹膜炎病毒 (FIPV) 感染的巨噬细胞释放的 TNF-a 促进中性粒细胞弹性蛋白酶的产生，第 151 届日本兽医学会年会

• 发表时间: 2011
• 作者: 高野友美;西山友理;佐藤美幸;早坂惇郎;東奈都子;中村美智代;佐藤亮一;宝達勉
• 通讯作者: 宝達勉

猫伝染性腹膜炎(FIP)発症猫における滲出液貯留と血管内皮細胞増殖因子(VEGF)の関係

猫传染性腹膜炎（FIP）渗出物积累与血管内皮生长因子（VEGF）的关系

• 发表时间: 2010
• 作者: 高野友美;大山拓;黒元愛子;佐藤亮一;宝達勉;柿崎竹彦;高野友美
• 通讯作者: 高野友美