查看“Margenza”的源代码

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            <strong>[[Margenza]]</strong>（通用名：<strong>[[玛格妥昔单抗]]</strong>）是一种创新的人源化 <strong>[[Fc 优化型]]</strong> 抗 <strong>[[HER2]]</strong> 单克隆抗体。该药物在 <strong>[[曲妥珠单抗]]</strong> 的序列基础上，利用 <strong>[[MacroGenics]]</strong> 专有的 Fc 优化平台，通过五个氨基酸的置换增强了抗体与激活型 Fc 受体（<strong>[[CD16A]]</strong>）的结合力。<strong>[[Margenza]]</strong> 旨在通过增强 <strong>[[抗体依赖性细胞毒性]]</strong>（ADCC）效应，为经治的晚期 <strong>[[HER2 阳性乳腺癌]]</strong> 患者提供更强的免疫杀伤效力。目前，该药已获 <strong>[[FDA]]</strong> 与 <strong>[[NMPA]]</strong> 批准，联合化疗用于转移性乳腺癌的三线及后线治疗。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">Margenza (Margetuximab)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">抗 HER2 Fc 优化单抗 · 点击展开</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶标：<strong>[[HER2]]</strong> (ERBB2)</div>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;"><strong>[[Entrez]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2064 (<strong>[[ERBB2]]</strong>)</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P04626</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约 149 kDa</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发厂家</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">MacroGenics / <strong>[[再鼎医药]]</strong></td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药途径</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">静脉滴注 (IV)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">审批状态</th>
                    <td style="padding: 12px; color: #16a34a;"><strong>[[FDA]]</strong>/<strong>[[NMPA]]</strong> 已上市</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;">药理机制：免疫监视的二次强化</h2>
    
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        <strong>[[Margenza]]</strong> 的抗肿瘤机制由直接的受体抑制与强化的免疫介导杀伤共同构成：
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        <li style="margin-bottom: 12px;">靶向 HER2 轴阻断：其 <strong>[[Fab 段]]</strong> 与 <strong>[[曲妥珠单抗]]</strong> 具有相似的结合表位，能够抑制 <strong>[[HER2]]</strong> 受体的二聚化及其下游信号通路的激活。</li>
        <li style="margin-bottom: 12px;">Fc 结构域工程化：通过对 Fc 段五个关键位置的氨基酸进行修饰（L235V, F243L, R292P, Y300L, P396L），显著增强了与 <strong>[[NK 细胞]]</strong> 及 <strong>[[巨噬细胞]]</strong> 表面 <strong>[[CD16A]]</strong> 受体的结合亲和力。</li>
        <li style="margin-bottom: 12px;">克服遗传多态性壁垒：传统抗体对携带 <strong>[[CD16A-158F]]</strong> 等位基因（约占人群 85%）的患者亲和力较低。Margenza 的设计专门针对这一庞大群体进行了优化，旨在提供更一致的 <strong>[[ADCC]]</strong> 临床响应。</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：SOPHIA 关键研究矩阵</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">评价维度</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">Margenza + 化疗 (n=266)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义分析</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">无进展生存期 (PFS)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">5.8 个月 (优势人群 6.9 个月)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">对比曲妥珠单抗显著延长，风险降低 24%。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">客观缓解率 (ORR)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">22%</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">展现出更高的缩瘤效能。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">安全性特征</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;" colspan="2;">最常见 3 级不良事件为 <strong>[[输注相关反应]]</strong> (IRR)；心脏毒性发生率与曲妥珠单抗相当。</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;">诊疗策略：多线治疗后的免疫挽救</h2>
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        在临床实践中，<strong>[[Margenza]]</strong> 的应用标志着对患者免疫效应器表型的关注：
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    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;">适应症选择：主要用于已接受过两种或以上抗 HER2 治疗方案（包括 <strong>[[T-DM1]]</strong>）的转移性 <strong>[[HER2 阳性乳腺癌]]</strong> 患者。</li>
        <li style="margin-bottom: 12px;">化疗配伍建议：通常联合 <strong>[[卡培他滨]]</strong>、艾立布林或吉西他滨等标准化疗方案使用。</li>
        <li style="margin-bottom: 12px;">安全性预防措施：鉴于输注相关反应发生率较高，建议首剂输注时密切观察，并在后续给药中根据患者反应调整输注速率。</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>[[ADCC]]</strong>：抗体依赖性细胞毒性，是单抗药物的核心免疫功能。</li>
            <li style="margin-bottom: 8px;"><strong>[[CD16A]]</strong>：NK 细胞表面的激活型受体，其基因多态性影响抗体疗效。</li>
            <li style="margin-bottom: 8px;"><strong>[[DS-8201]]</strong> (T-DXd)：目前 HER2 领域最强 ADC 药物，与 Margenza 构成差异化补充。</li>
            <li style="margin-bottom: 8px;"><strong>[[再鼎医药]]</strong>：该药在大中华区的商业化合作伙伴。</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>Rugo HS, et al. (2021).</strong> <em>Margetuximab versus trastuzumab in patients with previously treated HER2-positive metastatic breast cancer (SOPHIA): primary onset of progression-free survival results of a phase 3 trial.</em> <strong>[[The Lancet Oncology]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：SOPHIA 试验确立了 Margenza 在抗 HER2 多线治疗失败后的重要补充地位。</span>
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            [2] <strong>MacroGenics Pipeline Review. (2024).</strong> <em>Engineering the next generation of therapeutic antibodies: The role of Fc optimization.</em> <strong>[[Annual Review of Medicine]]</strong> (related review).[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：总结了 Margenza 如何通过精准的 Fc 工程化打破了传统单抗在低亲和力受体人群中的疗效瓶颈。</span>
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            Margenza (Margetuximab) 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;"><strong>[[HER2]]</strong>•<strong>[[CD16A]]</strong>•<strong>[[CD32B]]</strong>•<strong>[[CD64]]</strong>•<strong>[[FCRG]]</strong></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;">同类管线</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[曲妥珠单抗]]</strong>•<strong>[[DS-8201]]</strong>•<strong>[[ARX788]]</strong>•<strong>[[RC48]]</strong>•<strong>[[伊尼妥单抗]]</strong></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;"><strong>[[MacroGenics]]</strong>•<strong>[[再鼎医药]]</strong>•<strong>[[FDA]]</strong>•<strong>[[NMPA]]</strong>•<strong>[[NCCN]]</strong></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;">前沿方向</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[联合免疫检查点治疗研究]]</strong>•<strong>[[胃癌二线治疗探索]]</strong>•<strong>[[新辅助治疗应用研究]]</strong>•<strong>[[克服曲妥珠单抗耐药策略]]</strong></td>
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