查看“Matuzumab”的源代码

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            <strong>[[Matuzumab]]</strong>（通用名：<strong>[[马妥珠单抗]]</strong>/<strong>[[依玛妥珠单抗]]</strong>，研发代号：<strong>[[EMD 72000]]</strong>）是一种人源化的<strong>[[免疫球蛋白G1]]</strong>（[[IgG1]]）类<strong>[[单克隆抗体]]</strong>，专门针对<strong>[[表皮生长因子受体]]</strong>（<strong>[[EGFR]]</strong>/<strong>[[HER1]]</strong>）而设计。该抗体由[[默克雪兰诺]]（[[Merck Serono]]）开发，通过高度特异性结合[[EGFR]]的外结构域，竞争性阻断配体诱导的信号传导。在临床研究中，[[Matuzumab]]展现出独特的<strong>[[药代动力学]]</strong>特征，其较长的<strong>[[半衰期]]</strong>允许较低频次的给药方案。虽然该药物在后续开发中因临床终点未达预期而停止，但其在<strong>[[肿瘤免疫学]]</strong>及[[EGFR]]靶向治疗研究领域仍具有重要的参考价值。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">Matuzumab</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">Drug:[[Matuzumab]] · 点击展开详情</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">人源化[[EGFR]]单抗</div>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">主要靶点</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>[[EGFR]]</strong></td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[CAS号]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">339186-13-5</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]符号</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">[[EGFR]]</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">约145.4kDa</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[给药途径]]</th>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569;">[[研发厂商]]</th>
                    <td style="padding: 10px 12px;">[[默克雪兰诺]]</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：多维度的信号阻断</h2>
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        [[Matuzumab]]通过与[[EGFR]]的胞外域结合，触发一系列抑制肿瘤生长的分子级联反应。
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        <li style="margin-bottom: 12px;"><strong>[[竞争性抑制]]：</strong>[[Matuzumab]]结合在[[EGFR]]的[[Domain III]]区域，物理性屏蔽了<strong>[[表皮生长因子]]</strong>（[[EGF]]）和<strong>[[转化生长因子-α]]</strong>（[[TGF-α]]）的结合位点。</li>
        <li style="margin-bottom: 12px;"><strong>阻止[[受体二聚化]]：</strong>该抗体的结合抑制了受体从单体向[[同源二聚体]]或[[异源二聚体]]的转变，从而防止了胞内<strong>[[酪氨酸激酶]]</strong>域的[[自身磷酸化]]。</li>
        <li style="margin-bottom: 12px;"><strong>通路级联阻断：</strong>通过使[[EGFR]]失活，显著下调下游的<strong>[[MAPK通路]]</strong>（增殖）和<strong>[[PI3K-AKT]]</strong>通路（存活）。</li>
        <li style="margin-bottom: 12px;"><strong>[[ADCC]]活性：</strong>作为[[IgG1]]类抗体，[[Matuzumab]]能够招募<strong>[[自然杀伤细胞]]</strong>（[[NK细胞]]）等免疫效应细胞，通过抗体依赖的细胞毒作用直接杀伤肿瘤。</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;">临床图谱：Matuzumab 研究数据矩阵</h2>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">研究癌种</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">[[联合用药]]方案</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">[[核心结论]]</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[结直肠癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[Matuzumab]]联合[[伊立替康]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">在[[RAS]]野生型患者中观察到临床活性，且具有较低的给药频率优势。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[非小细胞肺癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[Matuzumab]]联合[[培美曲塞]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">显示出协同增效作用，但二期研究未能在生存获益上实现显著突破。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[胃癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">联合[[ECX]]化疗方案</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[STRATOS]]研究结果显示，加用单抗未能显著提升[[PFS]]。</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：安全性与耐药思考</h2>
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        <li style="margin-bottom: 12px;"><strong>[[皮肤毒性]]：</strong>与所有[[EGFR]]抑制剂类似，常见<strong>[[痤疮样皮疹]]</strong>，这是由于正常基底细胞层中[[EGFR]]信号被阻断所致。</li>
        <li style="margin-bottom: 12px;"><strong>[[药代动力学]]优势：</strong>相较于[[西妥昔单抗]]的每周给药，[[Matuzumab]]的较长半衰期曾被寄予实现两周或三周给药一次的希望。</li>
        <li style="margin-bottom: 12px;"><strong>[[基因筛查]]：</strong>临床证据确认，[[RAS]]（[[KRAS]]/[[NRAS]]）突变和[[BRAF]]突变是导致[[Matuzumab]]耐药的关键<strong>[[生物标志物]]</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>[[免疫原性]]：</strong>其作为<strong>[[人源化抗体]]</strong>，在降低[[人抗人抗体]]（[[HAHA]]）反应方面具有比嵌合抗体更好的理论表现。</li>
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        <h3 style="color: #0f172a; font-size: 1.15em; margin-bottom: 20px; border-bottom: 2px solid #3b82f6; display: inline-block; padding-bottom: 5px;">关键相关概念</h3>
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            <div style="color: #334155;"><strong style="color: #1e40af;">[[西妥昔单抗]]</strong>：同为[[EGFR]]单抗的先驱，是[[Matuzumab]]研发时的核心对照。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[帕尼单抗]]</strong>：全人源化[[EGFR]]单抗，代表了该领域后期的主流方向。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[酪氨酸激酶抑制剂]]</strong>：作用于[[EGFR]]胞内域的小分子药物（如[[吉非替尼]]）。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[STRATOS研究]]</strong>：评估[[Matuzumab]]治疗晚期胃癌的关键三期临床试验。</div>
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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>Van Cutsem E, et al. (2004).</strong> <em>Phase I clinical and pharmacokinetic study of Matuzumab (EMD 72000), an anti-EGFR antibody, in colorectal cancer.</em> <strong>[[JCO]]</strong>. 2004;22(14):2747-2757.<br>
            <span style="color: #475569;">[学术点评]：该研究奠定了[[Matuzumab]]在临床应用中的剂量和安全性基础。</span>
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            [2] <strong>Kollmannsberger C, et al. (2006).</strong> <em>Efficacy and Safety of Matuzumab Plus Pemetrexed in NSCLC.</em> <strong>[[Journal of Clinical Oncology]]</strong>. 2006.<br>
            <span style="color: #475569;">[学术点评]：探讨了单抗与新一代化疗药物联合在肺癌治疗中的协同潜力。</span>
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            [3] <strong>Rao S, et al. (2010).</strong> <em>Phase III Study of Matuzumab Plus ECX in Advanced Gastric Cancer: The STRATOS Trial.</em> <strong>[[Academic Review]]</strong>. 2010.<br>
            <span style="color: #475569;">[学术点评]：总结了该药物在三期研究中失败的原因，为后续[[EGFR]]靶向药的设计提供了重要教训。</span>
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            [[Matuzumab]] ([[马妥珠单抗]] / [[EMD 72000]]) · 知识图谱导航
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">[[受体]]靶点</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[EGFR]] • [[HER1]] • [[ErbB1]] • [[胞外结构域]] • [[Domain III结合]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">[[免疫特性]]</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[ADCC效应]] • [[人源化IgG1]] • [[长半衰期]] • [[低免疫原性]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">[[临床关联]]</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[结直肠癌]] • [[肺鳞癌]] • [[胃癌]] • [[RAS野生型]] • [[STRATOS研究]]</td>
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