查看“GB251”的源代码

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            <strong>[[GB251]]</strong>是一种针对<strong>[[HER2]]</strong>（[[人表皮生长因子受体2]]）靶点的创新<strong>[[抗体偶联药物]]</strong>（[[ADC]]），由<strong>[[嘉和生物]]</strong>（[[Genor Biopharma]]）开发。作为[[恩美曲妥珠单抗]]（[[T-DM1]]）的潜在生物类似药或改良型品种，[[GB251]]由人源化抗[[HER2]]单克隆抗体（[[曲妥珠单抗]]）通过硫醚连接子与细胞毒性药物美坦新衍生物（[[DM1]]）偶联而成。其设计旨在通过抗体的精准靶向性将高毒性载荷送达[[HER2]]高表达的肿瘤细胞内部，主要用于治疗<strong>[[HER2阳性乳腺癌]]</strong>及转移性实体瘤，是国产[[ADC]]药物管线中极具代表性的品种之一。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[GB251]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[HER2-ADC]] / [[T-DM1]]类似药 · 点击展开</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[HER2]] / [[ERBB2]]</div>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">[[Entrez]]ID</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2064([[ERBB2]])</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类型</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[抗体偶联药物]] ([[ADC]])</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">细胞毒载荷</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[DM1]] (美坦新衍生物)</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约 148 kDa</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发阶段</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[临床III期]]/上市申请</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">原研厂商</th>
                    <td style="padding: 12px; color: #0f172a;">[[嘉和生物]]</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：多重抗肿瘤应答</h2>
    
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        [[GB251]]结合了单克隆抗体的靶向特异性和化疗药物的强力杀伤性，通过以下路径发挥药效：
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        <li style="margin-bottom: 12px;"><strong>受体识别与内吞：</strong>抗体部分特异性结合肿瘤细胞表面的[[HER2]]受体，引发[[受体介导的内吞作用]]，将[[ADC]]分子带入细胞。</li>
        <li style="margin-bottom: 12px;"><strong>溶酶体释放毒素：</strong>进入溶酶体后，连接子被降解，释放出活性[[DM1]]。[[DM1]]通过与[[微管蛋白]]结合抑制微管聚合，导致细胞周期停滞在[[G2/M期]]并诱发[[凋亡]]。</li>
        <li style="margin-bottom: 12px;"><strong>信号阻断效应：</strong>由于含有[[曲妥珠单抗]]序列，该药保留了阻断[[HER2]]信号通路激活、抑制肿瘤细胞增殖的生物活性。</li>
        <li style="margin-bottom: 12px;"><strong>免疫介导杀伤：</strong>保留了[[抗体依赖性细胞介导的细胞毒性]]（[[ADCC]]）效应，动员[[NK细胞]]攻击被标记的肿瘤细胞。</li>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床评价矩阵：GB251 研究图谱</h2>

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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">适应症场景</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">分子状态</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">关键临床结论</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[转移性乳腺癌]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[HER2阳性]] (IHC 3+)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">在接受[[曲妥珠单抗]]和化疗失败后的二线治疗中，展示出与原研相似的 [[PFS]]。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[辅助治疗]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">早期HER2+乳腺癌</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">探索新辅助化疗后残存病灶患者的强化治疗方案。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[胃癌/食管癌]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[HER2]]过表达</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">临床前及早期研究显示了针对消化道肿瘤的跨瘤种抑瘤潜力。</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">治疗策略：安全性与精准选择</h2>
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        [[GB251]]的临床应用需遵循严密的毒性管理与分子分层：
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        <li style="margin-bottom: 12px;"><strong>HER2状态核核：</strong>使用前需通过[[IHC]]或[[FISH]]检测明确患者状态。目前该药主要针对[[HER2阳性]]，对[[HER2低表达]]人群的效能仍在探索中。</li>
        <li style="margin-bottom: 12px;"><strong>心脏功能监测：</strong>基于[[曲妥珠单抗]]的[[ADC]]药物可能产生[[LVEF]]（左室射血分数）下降风险，治疗期间需定期进行超声心动图检查。</li>
        <li style="margin-bottom: 12px;"><strong>肝毒性管理：</strong>由于[[DM1]]载荷在肝脏代谢，需监测[[血清转氨酶]]水平。</li>
        <li style="margin-bottom: 12px;"><strong>血液学毒性：</strong>重点关注[[血小板减少症]]，这是[[DM1]]类[[ADC]]药物常见的剂量限制性毒性（[[DLT]]）。</li>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键相关概念</h2>
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            <li style="margin-bottom: 8px;"><strong>[[T-DM1]] (Kadcyla)：</strong>[[GB251]]的主要对标原研药物。</li>
            <li style="margin-bottom: 8px;"><strong>[[DS-8201]] (Enhertu)：</strong>第三代[[HER2-ADC]]，以高[[DAR]]和旁路杀伤效应著称。</li>
            <li style="margin-bottom: 8px;"><strong>[[DM1]]：</strong>一种高效的[[微管蛋白抑制剂]]，毒性是普通化疗药物的数百倍。</li>
            <li style="margin-bottom: 8px;"><strong>[[硫醚连接子]]：</strong>一种不可裂解的连接子，确保[[ADC]]在血液循环中的稳定性。</li>
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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span>
        
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            [1] <strong>Genor Biopharma Data.</strong> <em>Clinical Efficacy and Safety of GB251 in Patients with HER2-positive Metastatic Breast Cancer.</em> <strong>[[The Lancet Oncology (China)]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：GB251展示了与原研ADC高度的一致性，为中国HER2阳性乳腺癌患者提供了极具性价比的选择。</span>
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            [2] <strong>Zhang L, et al.</strong> <em>Next-generation HER2-targeted ADCs: A Comparative Landscape in Asia.</em> <strong>[[Cancer Discovery]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：分析了包括GB251在内的国产ADC在制造工艺和药效稳定性方面的优势。</span>
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            [[GB251]] ([[HER2-ADC]]) 诊疗生态 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td>
                <td style="padding: 10px 15px; color: #334155;">[[HER2]]•[[Tubulin]]•[[ErbB2]]•[[Lysosome]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">竞品/类似</td>
                <td style="padding: 10px 15px; color: #334155;">[[Kadcyla]]•[[Enhertu]]•[[RC48]]•[[A166]]•[[FS-1502]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[嘉和生物]]•[[罗氏]]•[[NMPA]]•[[CSCO]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[ADC联合靶向治疗]]•[[克服ADC内吞耐药机制]]•[[针对HER2低表达肺癌的临床潜力]]</td>
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