查看“Domvanalimab”的源代码

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            <strong>[[多万妥单抗]]([[Domvanalimab]])</strong>，研发代码为<strong>[[AB154]]</strong>，是一种在研的、具有高度特异性的全人源化<strong>[[IgG1]]</strong>型单克隆抗体，特异性靶向免疫检查点<strong>[[TIGIT]]</strong>。该药物由<strong>[[ArcusBiosciences]]</strong>与<strong>[[吉利德科学]]([[GileadSciences]])</strong>联合开发。与其它[[TIGIT]]抗体不同，[[Domvanalimab]]采用了特殊的<strong>[[Fc-silent]]</strong>（Fc效应静默）设计，旨在通过阻断[[TIGIT]]信号轴而不引起免疫细胞耗竭。在2026年的免疫治疗格局中，[[Domvanalimab]]联合[[PD-1]]抑制剂<strong>[[津博瑞利单抗]]([[Zimberelimab]])</strong>已在<strong>[[非小细胞肺癌]]([[NSCLC]])</strong>及<strong>[[上消化道肿瘤]]</strong>的一线治疗中展现出显著的协同增效潜力。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">多万妥单抗</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Domvanalimab (AB154)·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：[[TIGIT]]</div>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">201633</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;">30861</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q495A1</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145kDa</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;">Fc-silent IgG1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;">主要药企</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[Gilead]]/[[Arcus]]</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;">三期临床关键数据产出期</td>
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        [[Domvanalimab]]通过独特的药理设计，旨在最大化免疫激活效率而避免不必要的副作用：
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        <li style="margin-bottom: 12px;"><strong>阻断 TIGIT-PVR 轴：</strong>
            [[Domvanalimab]]高亲和力结合[[TIGIT]]，阻断其与配体<strong>[[CD155]]([[PVR]])</strong>的结合。这防止了抑制性信号的传递，并促使[[PVR]]结合活化受体<strong>[[CD226]]</strong>，从而增强T细胞活性。</li>
        <li style="margin-bottom: 12px;"><strong>Fc-silent 特性：</strong>
            与某些[[TIGIT]]单抗（如[[Ociperlimab]]）不同，[[Domvanalimab]]被设计为不具备效应功能（如[[ADCC]]）。2026年的免疫学共识认为，这种设计能防止对表达[[TIGIT]]的效应T细胞造成破坏，理论上在特定微环境中能保留更多的抗肿瘤免疫细胞。</li>
        <li style="margin-bottom: 12px;"><strong>三联免疫通路协同：</strong>
            [[Domvanalimab]]常与[[PD-1]]抑制剂及<strong>[[腺苷通路抑制剂]]</strong>（如[[Etrumadenant]]）联合，旨在从多个维度解除肿瘤微环境的免疫抑制。</li>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">研究代号</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">适应症场景(2026)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[ARC-7]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">晚期[[NSCLC]]一线治疗([[PD-L1]]≥50%)。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[Dom]]+[[Zim]]联合方案显著改善[[PFS]]，确立双免疫优势。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[STAR-121]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">晚期[[胃癌]]/[[食管癌]]一线治疗。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>关键III期</strong>。探索[[TIGIT]]在消化道肿瘤的突破。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[ARC-10]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[PD-L1]]高表达[[NSCLC]]的全球三期验证。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">旨在通过更大规模人群确立全球监管审批基础。</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：精准组合与安全性特征</h2>
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        [[Domvanalimab]]在临床实践中展现了优异的耐受性，其管理核心在于多靶点联动的协同：
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        <li style="margin-bottom: 12px;"><strong>免疫性副作用(irAE)谱系：</strong> 由于其[[Fc-silent]]设计，[[Domvanalimab]]在临床试验中未增加明显的脱靶毒性。2026规范指出，其联合方案的毒性特征与[[PD-1]]单药基本一致，重点仍是监测<strong>[[免疫性肺炎]]</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>生物标志物筛选：</strong> 目前研究集中在[[PD-L1]]高表达人群。2026年前沿观点正探索<strong>[[CD155]]</strong>和<strong>[[CD226]]</strong>的比例作为精准预测[[TIGIT]]阻断效果的辅助指标。</li>
        <li style="margin-bottom: 12px;"><strong>维持治疗策略：</strong> 针对初治获得缓解的患者，[[Domvanalimab]]联合[[津博瑞利单抗]]的低毒性特征使其成为理想的长期维持方案。</li>
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            <li style="margin-bottom: 8px;"><strong>[[Fc-silent]]：</strong> 旨在阻断信号而不介导细胞毒性的抗体改造技术。</li>
            <li style="margin-bottom: 8px;"><strong>[[津博瑞利单抗]]([[Zimberelimab]])：</strong> [[Domvanalimab]]在全球开发项目中的标准[[PD-1]]搭档。</li>
            <li style="margin-bottom: 8px;"><strong>[[TIGIT]]：</strong> 目前免疫肿瘤学中最受关注的抑制性辅助受体。</li>
            <li style="margin-bottom: 8px;"><strong>[[CD155]]([[PVR]])：</strong> 肿瘤细胞表面的核心免疫逃逸配体。</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>Johnson ML,et al.(2023/2025Revision).</strong> <em>Domvanalimab plus Zimberelimab in patients with untreated metastatic NSCLC:Results from the ARC-7 trial.</em> <strong>[[The Lancet Oncology]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：ARC-7研究确立了Fc-silent TIGIT阻断剂在肺癌联合治疗中的安全性与初步疗效。</span>
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            [2] <strong>Gilead Sciences Oncology Pipeline Report(2025/2026).</strong> <em>Mechanistic rationale for Fc-silent design in Domvanalimab:Preserving effector T-cell population.</em> [Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年的综述深度解析了多万妥单抗在维持T细胞存续方面的理论优势及其对长期预后的潜在贡献。</span>
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            多万妥单抗 (Domvanalimab) · 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;">[[TIGIT]]•[[PD-1]]•[[CD155]]•[[CD226]]•[[A2aR/A2bR]]</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;">治疗组合</td>
                <td style="padding: 10px 15px; color: #334155;">[[津博瑞利单抗]]•[[Etrumadenant]]•[[化疗联合]]</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;">竞争对手</td>
                <td style="padding: 10px 15px; color: #334155;">[[Tiragolumab]]•[[Ociperlimab]]•[[Vibostolimab]]</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;">核心试验</td>
                <td style="padding: 10px 15px; color: #334155;">[[ARC-7研究]]•[[STAR-121研究]]•[[ARC-10研究]]</td>
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