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$(document).ready(function(){ var d = setInterval(function() { var title = $.trim($("div[class*='c_portalResBreadcrumb_nav'] .e_breadcrumb:eq(2) .font span").text()); $("div[class*='c_portalResNews_category'] .js_categoryBox > div.p_parentBox:eq(0) > div.p_linkBox").addClass("click"); if(title != "") { $("div[class*='c_portalResNews_category'] .js_categoryBox .p_title:contains("+title+")").parent(".p_linkBox").addClass("click"); $("div[class*='c_portalResNews_category'] .js_categoryBox > div.p_parentBox:eq(0) > div.p_linkBox").removeClass("click"); } },500); }); </script> </div></div> </div> </div></div><div id="w_grid-1558317060682" class="w_grid-001"><div class="w_grid signal"> <div class="e_box e_box-000 p_gridbox"> <div id="content_box-1558317060682-0" class="e_box e_box-000 d_gridCell_0 p_gridCell"><div id="c_portalResNews_detail-15583178295403218" class="c_portalResNews_detail-01001"> <div class="e_box p_NewsDetail" data-ename="資訊詳情" data-infoid="116">    <div class="e_box p_topBox"> <div class="e_box p_header">   <div class="e_box p_TitleBoxA"> <h1 class="e_title h1 p_headA"> <div class="font"> 雙特異性抗體在腫瘤治療中的優勢 </div> </h1> </div> </div> <ul class="e_box p_dataSource borderT_default" data-ename="資訊信息">  <li><span class="i_pubDate">發布時間：</span>2021-08-09 11:13</li> <li><span class="i_pvs">訪問量：</span><span class="p_viewCount">0</span></li> </ul>  <p class="e_article p_summary background_info" data-ename="資訊概要信息"> <span><span class="i_SummaryBox">【概要描述】</span></span>是指可以與兩個不同抗原或同一抗原的兩個不同抗原表位相結合的抗體，具有明確功能的雙特異性抗體在自然條件下并不存在，一般是通過細胞融合技術或者重組DNA技術等人工手段得到的。 </p>  </div>  <div class="e_box p_infoBox">  <div class="e_box p_header">   <div class="e_box p_TitleBoxA"> <h1 class="e_title p_headA h3 font_thick"> <div class="font"> <i class="iconfont"></i> 雙特異性抗體在腫瘤治療中的優勢 </div> </h1> </div> </div>  <p class="e_article p_summary" data-ename="資訊概要信息"> <span><span class="i_SummaryBox">【概要描述】</span></span>是指可以與兩個不同抗原或同一抗原的兩個不同抗原表位相結合的抗體，具有明確功能的雙特異性抗體在自然條件下并不存在，一般是通過細胞融合技術或者重組DNA技術等人工手段得到的。 </p> <ul class="e_box p_dataSource e_box p_dataSource borderB_default" data-ename="資訊信息"> <li><span class="i_sort">分類：</span><a href="/news/新聞中心-5">新聞中心</a></li> <li><span class="i_auth">作者：</span>馮夢雪</li> <li><span class="i_source">來源：</span></li>  <li><span class="i_pubDate">發布時間：</span>2021-08-09 11:13</li> <li><span class="i_pvs">訪問量：</span><span class="p_viewCount">0</span></li> </ul>  </div>  <div class="e_title p_articlesTitle" data-ename="描述標題"> <div class="font">詳情 </div> </div> <div class="e_box p_articles" data-ename="資訊詳細描述"><section><span style="font-size:16px;">? <span style="color:#c0392b;">雙特異性抗體（Bispecific Antibody，BsAb），簡稱雙抗，是指可以與兩個不同抗原或同一抗原的兩個不同抗原表位相結合的抗體<sup>[1]</sup>，</span>具有明確功能的雙特異性抗體在自然條件下并不存在，一般是通過細胞融合技術或者重組DNA技術等人工手段得到的。</span></section> <section><span style="font-size:16px;"> </span></section> <section><span style="font-size:18px;"> <strong>相比于普通的單抗，雙特異性抗體優勢明顯：</strong></span></section> <section><span style="font-size:16px;"><span style="background-color:#c0392b;">①</span>可減少藥物開發和臨床試驗成本；</span></section> <section><span style="font-size:16px;"><span style="background-color:#c0392b;">②</span>雙特異性抗體的治療效果明顯優于兩種或多種單抗聯合應用，雙特異性抗體可使靶細胞表面受體形成網狀連接，進而形成受體聚集物，從而提高抗體對腫瘤細胞的抑制作用，并且對傳統單抗難以起效的低表達細胞亦有顯著效果。</span></section> <section><span style="font-size:16px;"><span style="background-color:#c0392b;">③</span>相對于單抗靶向治療以及多種單抗聯合治療，雙特異性抗體能夠降低藥物的耐受性，并且副作用較小<sup>[2]</sup>。所以雙抗在臨床等方面有著巨大的前景。</span></section> <section> </section> <section><span style="font-size:16px;"> 雙抗目前主流的治療研究領域有抗腫瘤、自身免疫病及其他疾病等，其中以抗腫瘤的研究居多?，F階段的腫瘤治療主要是以改善癥狀、延長生存期為目的，一些常見的抗腫瘤方法有手術、化療、放療、靶向治療、免疫治療等等，雙特異性藥物的出現為腫瘤治療帶來新的希望。</span></section> <section> </section> <section><span style="font-size:16px;"> 雙特異性抗體在腫瘤治療中的一個重要機制就是介導免疫細胞殺傷，同時靶向腫瘤抗原與效應細胞抗原，從而激活效應細胞殺傷靶細胞，另外它還可以進行雙靶點信號阻斷，有效防止腫瘤耐藥性的產生<sup>[3]</sup>。下面詳述一下雙特異性抗體的作用機制：</span></section> <p> </p> <p style="text-align: center;"><img data-galleryid="" data-ratio="0.7550335570469798" data-s="300,640" data-type="png" data-w="596" src="https://mmbiz.qpic.cn/mmbiz_png/GD0TrhM0VMGGfkSBbrU7wTg9JvL83IIojVXA0Y8ibuSFyHabVDXPwfSDmNIGnAc8rW5DCu92N0lLUPuYfibuRa0g/640?wx_fmt=png" /></p> <p style="text-align: center;">圖1: 雙特異性抗體的作用機制</p> <p style="text-align: center;"> <img data-imgqrcoded="1" data-ratio="0.33275862068965517" data-s="300,640" data-type="png" data-w="580" src="https://mmbiz.qpic.cn/mmbiz_png/GD0TrhM0VMGGfkSBbrU7wTg9JvL83IIoBXg01ZMiaSmvVFTan8WRfhzKC1lezxy10PeFx9HlpcKQhJfLsHcGwpg/640?wx_fmt=png" /></p> <p style="text-align: center;"><strong> <span style="font-size:22px;"> 介導免疫</span></strong><span style="font-size:22px;"><strong>細胞殺傷</strong></span></p> <p> </p> <section><br /> <span style="font-size:16px;"> 雙特異性抗體有兩條抗原結合臂，其中一條與靶抗原結合，另一條與效應細胞上的標志抗原結合，后者可以激活效應細胞，使其靶向殺滅腫瘤細胞（如圖1a）。以Catumaxomab（卡妥索單抗）為例，兩個抗原結合臂分別結合細胞毒性T細胞的CD3位點和腫瘤細胞的 EpCAM 位點，從而引導T細胞殺傷靶細胞。</span></section> <p><strong> </strong></p> <p style="text-align: center;"><strong> <img data-ratio="0.3383333333333333" data-s="300,640" data-type="png" data-w="600" src="https://mmbiz.qpic.cn/mmbiz_png/GD0TrhM0VMGGfkSBbrU7wTg9JvL83IIoQfl71m4czcOvOzWibP6xc3J5vzdic081fib5Gu7F1BO6ZlVibibCia9BkiaicA/640?wx_fmt=png" /></strong></p> <p style="text-align: center;"><strong> <span style="font-size:22px;"> 雙靶點</span></strong><span style="font-size:22px;"><strong>信號阻斷</strong></span></p> <section> </section> <section><span style="font-size:16px;"> 同時結合雙靶點，阻斷雙信號通路是雙特異性抗體的另一個重要作用機制（如圖1b、c）。</span></section> <p><span style="font-size:16px;"> 受體酪氨酸激酶(receptor tyrosine kinase，RTKs) 是最大的一類酶聯受體，在細胞增殖過程中發揮重要調節作用，如 Her 家族等。RTKs 在腫瘤細胞表面異常高表達，導致腫瘤細胞惡性增生，因此也是腫瘤治療的重要靶點<sup>[4]</sup>。針對RTKs 的單靶點單克隆抗體已在腫瘤治療中得到廣泛應用。</span></p> <p> </p> <p><span style="font-size:16px;"> 但是，腫瘤細胞可以通過轉換信號通路或通過HER家族成員自身或不同成員之間的同源或異源二聚體激活細胞內信號進行免疫逃逸，因此采用雙特異性抗體藥物同時滅活兩個或多個RTKs或其配體，可以減少腫瘤細胞逃逸，提高治療效果。</span></p> <section> </section> <p style="text-align: center;"><img data-galleryid="" data-imgqrcoded="1" data-ratio="0.4711191335740072" data-s="300,640" data-type="png" data-w="554" src="https://mmbiz.qpic.cn/mmbiz_png/GD0TrhM0VMGGfkSBbrU7wTg9JvL83IIoN37002pEvbRyhjZdbpj6vNia01ncBWpBbsXhT5oQAOicGc2DiaDoxDPJA/640?wx_fmt=png" /></p> <p style="text-align: center;">圖2：雙靶點信號阻斷作用原理</p> <p> </p> <p style="text-align: center;"><strong> <img data-ratio="0.33" data-s="300,640" data-type="png" data-w="600" src="https://mmbiz.qpic.cn/mmbiz_png/GD0TrhM0VMGGfkSBbrU7wTg9JvL83IIofTlfbzs2QW8j0kx7zty5GyF512wJ6kqKK0uOrGZ0PahbqWnue97qQg/640?wx_fmt=png" /></strong></p> <p style="text-align: center;"><strong> <span style="font-size:22px;"> 促進蛋白形成功能性復合體</span></strong></p> <section> </section> <p><span style="font-size:16px;"> 利用雙特異性抗體兩個抗原結合臂可以結合不同抗原的特點，兩個抗原結合臂分別結合兩種特定蛋白分子，形成功能性復合體。利用該種復合體給藥，可以減少機體內排斥反應，提高臨床治療效果。</span></p> <p style="text-align: center;"><img data-galleryid="" data-imgqrcoded="1" data-ratio="0.5399610136452242" data-s="300,640" data-type="png" data-w="513" src="https://mmbiz.qpic.cn/mmbiz_png/GD0TrhM0VMGGfkSBbrU7wTg9JvL83IIoUJ9NbPP5hNnub1ZoXb7UmC39v1k1I5ENWIrNB5pg4yMJE1qv3swf3w/640?wx_fmt=png" /></p> <p style="text-align: center;">圖3：促進蛋白形成功能性復合體作用原理</p> <section> </section> <section><span style="font-size:16px;"> 在如今生物制劑的研發大潮中，抗體藥物蓬勃發展，雙特異性抗體的優勢更是讓我們看到了這一領域進一步發展的巨大潛力。</span></section> <section> </section> <section><span style="font-size:16px;"> 目前，雙特異性抗體在眾多腫瘤類型治療中的應用仍然處于臨床前研究或者進入臨床研究階段，作為一門前沿技術，雙特異性抗體的研發在質量分析控制、合理評價動物模型、臨床研究策略以及規?；a等方面仍存在諸多挑戰<sup>[5]</sup>。</span></section> <section> </section> <section><span style="font-size:16px;"> 相信隨著對雙特異性抗體的研究越來越深入，未來雙特異性抗體在腫瘤治療領域一定會有更廣闊的應用空間。</span></section> <p style="text-align: center;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/GD0TrhM0VMGVOc2G7tXWTNkVX7K0Tps2FmkrejOvmT4fkscaibX8ZpVJSurap30mr6nicC3u42xDy3ofKniaZZt5A/640?wx_fmt=jpeg" style="width: 840px; height: 452px;" /></p> <section> </section> <section>參考文獻</section> <section>[1] Fan G, Wang Z, Hao M, et al. Bispecific antibodies and their applications[J].J Hematol Oncol,2015,8(1):130.</section> <section>[2]魏雪晨,顏煒群.雙特異性抗體的作用機制及制備與純化方法研究進展[J].生物技術,2021,31(01):89-95.</section> <section>[3]王璐瑤,魏振華,熊偉佳,白素杭,喻長遠,楊昭.雙特異性抗體構建在腫瘤臨床治療中的應用[J].生物工程學報,2021,37(02):513-529.</section> <section>[4]尚明英,馬祥君,蔡少青.從天然產物中尋找酪氨酸蛋白激酶(PTKs)抑制劑的研究進展[J].中草藥,1997(07):433-437.</section> <section>[5]陳小青,陳奮天,羅文新.靶向免疫檢查點的雙特異性抗體在腫瘤治療中的研究進展[J].腫瘤研究與臨床,2021,33(03):221-225.</section> </div>  <div class="e_box p_KeywordBox" data-ename="關鍵詞"> <span class="i_keywordLabel">關鍵詞：</span> <p class="p_tags"> <button data-foreachitem type="button" class="btn btn-default">抗體</button> <button data-foreachitem type="button" class="btn btn-default">特異性</button> <button data-foreachitem type="button" class="btn btn-default">腫瘤</button> <button data-foreachitem type="button" class="btn btn-default">細胞</button> <button data-foreachitem type="button" class="btn btn-default">治療</button> <button data-foreachitem type="button" class="btn btn-default">抗原</button> <button data-foreachitem type="button" class="btn btn-default">結合</button> <button data-foreachitem type="button" class="btn btn-default">臨床</button> </p> </div> <div class="e_box p_QRCode borderT_default" data-ename="打開手機查看"> <p class="e_title p_SaveText" data-ename="二維碼引導信息"><span class="i_qrcode">掃二維碼用手機看</span></p> <p class="e_image js_qrcode" data-ename="二維碼"></p> </div>  <div class="e_box d_pcDom p_PrevAndNext borderB_default" data-ename="上一篇、下一篇信息區"> <div class="e_box p_previewBox"> <span class="i_title"><span class="i_pageUpTitle">上一個</span><span class="clons">:</span></span> <a href="/news/外泌體，被錯認的細胞“垃圾袋”-117.html" data-ename="上一篇信息區"> <span class="p_PreviewTitle">外泌體，被錯認的細胞“垃圾袋”</span> </a> </div>  <div class="e_box p_nextBox"> <span class="i_title"><span class="i_pageDownTitle">下一個</span><span class="clons">:</span></span> <a href="/news/一文讀懂H3K27me3-115.html" data-ename="下一篇標題"> <span class="p_PreviewTitle">一文讀懂H3K27me3</span> </a> </div> </div>   <div class="e_box p_PrevAndNextMo p_PrevAndNext borderB_default" data-ename="上一篇、下一篇信息區"> <div class="e_box p_previewBox"> <span class="i_title"><span class="i_pageUpTitle">上一個</span><span class="clons">:</span></span> <a href="/news/外泌體，被錯認的細胞“垃圾袋”-117.html" data-ename="上一篇信息區"> <span class="p_PreviewTitle">外泌體，被錯認的細胞“垃圾袋”</span> </a> </div>  <div class="e_box p_nextBox"> <span class="i_title"><span class="i_pageDownTitle">下一個</span><span class="clons">:</span></span> <a href="/news/一文讀懂H3K27me3-115.html" data-ename="下一篇標題"> <span class="p_PreviewTitle">一文讀懂H3K27me3</span> </a> </div> </div>  </div> <script type="text/javascript"> $comp({ params: { imgRelativeData: { params: { bigPicBox: 'p_img',//大圖片盒子 nextPicBtn: 'p_SwitchBtnB',//大圖片右按鈕 prePicBtn: 'p_SwitchBtnA',//大圖片左按鈕 describeBox: 'p_SummaryBox',//圖片說明盒子 curNum:'p_curNum',//描述圖片中當前是第幾個 bigPicList:'p_imgLink',//圖片鏈接到 describeTitle: 'p_ImgHead',//圖片說明文字標題 describeText: 'p_ImgSummary',//圖片說明文字描述 nextPageBtn: 'p_SwitchBtnD',//小圖列表右按鈕 prePageBtn: 'p_SwitchBtnC',//小圖列表左按鈕 picList: 'p_thumbnail',//小圖列表圖片 isCarousel: true,//是否循環顯示 picNum: 4,//縮略圖一屏顯示個數， //大圖顯示比例 imageWidth: 4, imageHeight: 3, //小圖圖顯示比例 sImageWidth: 4, sImageHeight: 3 } }, "c_qrcode": "", //二維碼地址 "qrcodeWidth": "100", //二維碼寬高 "qrcodeHeight": "100", "isCheckedCustom": true, //true 檢查錯誤圖片，false不檢查 "defaultNoPicture": "/public/img/no-img.svg", //錯誤圖片時顯示的圖片 "isOpenBigCutMode": true, //大圖 true是裁剪，false是留白 "isOpenSmallCutMode": true, //縮略圖 true是裁剪，false是留白 "autoPlay": false, }, //el等參數 id: "portalResNews_detail-15583178295403218",//實例id 服務器傳 lib: ["js/portalNews/portalResNews_detail-01"], //組件js noDataFlag:"" }); </script> </div></div> </div> </div></div></div> </div> </div></div><div id="w_grid-1554899886322" class="w_grid-000"><div class="w_grid signal"> <div class="e_box e_box-000 p_gridbox"> <div id="content_box-1554899886322-0" class="e_box e_box-000 d_gridCell_0 p_gridCell"><div id="w_grid-1554899886331" class="w_grid-001"><div class="w_grid "> <div class="e_box e_box-000 p_gridbox"> <div id="content_box-1554899886331-0" class="e_box e_box-000 d_gridCell_0 p_gridCell"><div id="w_fimg-1554899886344" class="w_fimg-000"><div class="w_img animated "> <div class="e_box e_box-000 p_box"> <a class="e_link e_link-000 p_link001" target="_blank"> <div class="e_image e_DImage-001 p_dimage"> <img src="http://img201.yun300.cn/img/logo_yrk12.png?tenantId=137972&viewType=1&k=1678932544000" alt="飛悅?？? 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