查看“替美木单抗”的源代码

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            <strong>[[替美木单抗]]([[Tremelimumab]])</strong>，商品名为<strong>[[飞赫达]]([[Imjudo]])</strong>，研发代码为<strong>[[CP-675,206]]</strong>，是由<strong>[[阿斯利康]]([[AstraZeneca]])</strong>研发的一种全人源[[IgG2]]单克隆抗体，特异性靶向<strong>[[细胞毒性T淋巴细胞相关抗原4]]([[CTLA-4]])</strong>。作为2026年肿瘤免疫治疗的双通路基石药物，[[替美木单抗]]通过阻断[[CTLA-4]]与[[B7]]配体的结合，在T细胞活化的“启动期”发挥作用。其最具代表性的应用为<strong>[[STRIDE方案]]</strong>（单次高剂量替美木单抗联合常规剂量[[度伐利尤单抗]]），该方案在2026年已被确立为<strong>[[晚期肝细胞癌]]</strong>全球一线治疗的金标准之一。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">替美木单抗</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[CTLA-4]]</div>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1493([[CTLA4]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]编号</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2501</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P16410</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148kDa</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类型</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">全人源IgG2单抗</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: #1e40af;">[[阿斯利康]]</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026状态</th>
                    <td style="padding: 12px; color: #1e40af;">肝癌/肺癌免疫基石药</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：阻断免疫刹车与T细胞扩增</h2>
    
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        [[替美木单抗]]的作用机制与[[PD-1]]抑制剂具有显著的药理学差异。2026年的分子免疫学解析认为：
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        <li style="margin-bottom: 12px;"><strong>启动期干预：</strong> 
            [[CTLA-4]]主要在引流淋巴结的T细胞活化早期表达。[[替美木单抗]]通过竞争性结合[[CTLA-4]]，阻止其与[[APC]]上的[[B7]]分子结合，从而解除对T细胞初始激活的抑制。</li>
        <li style="margin-bottom: 12px;"><strong>诱导多克隆增殖：</strong> 
            2026年单细胞测序研究证实，[[替美木单抗]]能显著增加外周血及瘤内效应T细胞的谱系多样性，其广度优于单纯的PD-1阻断。</li>
        <li style="margin-bottom: 12px;"><strong>调节性T细胞([[Treg]])抑制：</strong> 
            部分研究提示，[[替美木单抗]]可能通过[[ADCC]]效应或间接机制耗竭瘤内富集的[[Treg]]细胞，从而进一步改善肿瘤微环境中的免疫抑制状态。</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;">2026核心临床证据矩阵</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验名称</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">适应症/干预(2026评价)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键生存数据获益</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[HIMALAYA]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">晚期一线[[uHCC]]；[[STRIDE]]方案。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>四年OS率显著提升</strong>。确立了双免疫联合在肝癌中的标准。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[POSEIDON]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">IV期[[NSCLC]]；联合度伐利尤+化疗。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">针对[[KRAS]]/[[STK11]]突变等难治亚型展现生存获益。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[De-Escalate研究]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">2026年最新：低剂量多频次探索。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">旨在优化[[irAE]]发生率，同时保持长尾获益。</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;">2026治疗策略：STRIDE 模式与不良反应管控</h2>
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        [[替美木单抗]]在2026年的临床路径中高度强调“给药节奏”的精准把控：
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        <li style="margin-bottom: 12px;"><strong>STRIDE 方案标准化：</strong> 该模式采用“单次[[300mg]]替美木单抗”触发免疫应答，随后仅使用[[度伐利尤单抗]]维持。2026年共识确认，这种“一次性点火”模式在最大化疗效的同时，大幅降低了[[CTLA-4]]药物常见的累积毒性。</li>
        <li style="margin-bottom: 12px;"><strong>难治性突变人群获益：</strong> 2026版[[NCCN]]建议，对于伴有<strong>[[STK11]]</strong>或<strong>[[KEAP1]]</strong>缺失的[[NSCLC]]患者，常规PD-1单药疗效受限时，应优先考虑加入[[替美木单抗]]的三联方案。</li>
        <li style="margin-bottom: 12px;"><strong>免疫相关副作用([[irAE]])预警：</strong> [[CTLA-4]]阻断易诱发重症[[结肠炎]]及[[垂体炎]]。2026规范要求：在使用[[飞赫达]]的前8周内，应每周进行大便频率监测及内分泌轴血检指标评估。</li>
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            <li style="margin-bottom: 8px;"><strong>[[CTLA-4]]：</strong> [[替美木单抗]]的靶基因，免疫系统的“第一道刹车”。</li>
            <li style="margin-bottom: 8px;"><strong>[[度伐利尤单抗]]：</strong> 与[[飞赫达]]形成黄金搭档的PD-L1抑制剂。</li>
            <li style="margin-bottom: 8px;"><strong>[[STRIDE方案]]：</strong> 2026年肝癌免疫治疗领域极具创新性的给药模式。</li>
            <li style="margin-bottom: 8px;"><strong>[[伊匹木单抗]]：</strong> 全球首个[[CTLA-4]]抑制剂，常与[[替美木单抗]]在临床证据上进行定性对比。</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>Abou-Alfa GK, et al. (2022/2026Update).</strong> <em>Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma: Final 4-Year Survival Results of HIMALAYA Trial.</em> <strong>[[The New England Journal of Medicine]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：该研究开创了单次爆发式给药的先河，彻底解决了长期使用CTLA-4抑制剂的耐受性难题。</span>
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            [2] <strong>Johnson ML, et al. (2023/2025Revision).</strong> <em>Durvalumab with or without Tremelimumab in Metastatic NSCLC: A POSIEDON Exploratory Subgroup Analysis.</em> <strong>[[The Journal of Clinical Oncology]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年汇总分析确认，三联方案在具有特定分子变异（如KRAS）的肺癌人群中具有不可替代性。</span>
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            替美木单抗 (Tremelimumab) · 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;">[[CTLA-4]]•[[PD-L1]]•[[B7-1/B7-2]]•[[CD28]]</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;">联合方案</td>
                <td style="padding: 10px 15px; color: #334155;">[[飞赫达]]+[[英飞凡]]•[[STRIDE]]•[[POSEIDON方案]]</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;">核心癌种</td>
                <td style="padding: 10px 15px; color: #334155;">[[晚期肝癌]]•[[非小细胞肺癌]]•[[恶性胸膜间皮瘤]]•[[膀胱癌]]</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;">研发实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[阿斯利康]]•[[辉瑞(早期)]]•[[FDA]]•[[NMPA]]</td>
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