查看“Zynlonta”的源代码

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            <strong>[[Loncastuximab]]</strong>（全称：<strong>[[Loncastuximab Tesirine]]</strong>，通用名为<strong>[[奥隆司妥单抗]]</strong>），商品名为 <strong>[[Zynlonta]]</strong>，研发代码为 <strong>[[ADCT-402]]</strong>，是由 <strong>[[ADC Therapeutics]]</strong> 研发的一种针对 <strong>[[CD19]]</strong> 靶点的首创 <strong>[[抗体偶联药物]]</strong>（<strong>[[ADC]]</strong>）。该药物由人源化 IgG1 抗体与强效 DNA 跨链结合剂 <strong>[[PBD]]</strong>（吡咯并苯二氮卓）二聚体偶联而成。<strong>[[Loncastuximab]]</strong> 主要用于治疗 <strong>[[复发或难治性大B细胞淋巴瘤]]</strong>（<strong>[[R/R DLBCL]]</strong>），是全球首个获批用于该适应症的针对 <strong>[[CD19]]</strong> 的 <strong>[[ADC]]</strong>。作为一种现货型疗法，它为既往接受过多种方案（包括 <strong>[[CAR-T]]</strong> 细胞疗法）后进展的淋巴瘤患者提供了关键的补救治疗手段。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">Zynlonta (奥隆司妥单抗)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Loncastuximab Tesirine · ADCT-402</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px;">核心靶点：<strong>[[CD19]]</strong></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%; font-weight: normal;"><strong>[[Entrez]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">930 (<strong>[[CD19]]</strong>)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;"><strong>[[HGNC]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1633</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">药物荷载</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;"><strong>[[SG3199]]</strong> (PBD Dimer)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">平均DAR</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2.3</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">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; border-bottom: 1px solid #e2e8f0; font-weight: normal;">研发厂家</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;"><strong>[[ADC Therapeutics]]</strong></td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; font-weight: normal;">审批状态</th>
                    <td style="padding: 12px; color: #16a34a;">FDA 已获批</td>
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        <strong>[[Loncastuximab]]</strong> 的作用原理结合了抗体的精准定位能力与 <strong>[[PBD]]</strong> 毒素的极高细胞毒性：
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        <li style="margin-bottom: 12px;">靶向识别：药物的人源化抗体部分特异性结合 B 细胞表面的 <strong>[[CD19]]</strong> 抗原。该靶点在弥漫大 B 细胞淋巴瘤等病灶中表达非常稳定。</li>
        <li style="margin-bottom: 12px;">毒素释放：<strong>[[ADC]]</strong> 复合物被内吞进入溶酶体后，通过蛋白酶切割释放出活性载荷 <strong>[[SG3199]]</strong>。</li>
        <li style="margin-bottom: 12px;">DNA 交联：<strong>[[PBD]]</strong>（吡咯并苯二氮卓）二聚体通过结合 DNA 小沟，在两条链之间形成不可逆的共价交联，彻底阻断 DNA 复制和转录，导致肿瘤细胞凋亡。</li>
        <li style="margin-bottom: 12px;">细胞周期无关性：由于直接作用于 DNA 结构，该药不仅杀伤分裂期细胞，对静止期的肿瘤克隆亦有显著清除作用。</li>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%; font-weight: bold;">研究维度</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569; font-weight: bold;"><strong>[[LOTIS-2]]</strong> 研究结果</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af; font-weight: bold;">临床意义</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1;">客观缓解率 (ORR)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">48.3%</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">在多线复发难治患者中展现了极高的缓解率。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1;">完全缓解率 (CR)</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">24.8%</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">约四分之一的重症患者实现了病灶完全消失。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[CAR-T]]</strong> 经治获益</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">ORR 约 46%</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">证明了其对 <strong>[[CAR-T]]</strong> 失败人群的有效挽救能力。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1;">安全性表现</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;" colspan="2;">常见中性粒细胞减少、<strong>[[GGT]]</strong> 升高及特征性的 <strong>[[水肿]]</strong> 风险。</td>
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        临床应用 <strong>[[Loncastuximab]]</strong> 时，需重点关注其独特的安全性图谱与用药便利性：
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        <li style="margin-bottom: 12px;">即买即用：相比制备周期较长的 <strong>[[CAR-T]]</strong> 疗法，该药作为现货药物，可为进展迅速的患者提供即时治疗。</li>
        <li style="margin-bottom: 12px;"><strong>[[浆膜腔积液]]</strong> 防治：载荷 <strong>[[PBD]]</strong> 可能引发胸水或腹水。指南建议给药前一天开始连续三天口服 <strong>[[地塞米松]]</strong>（4mg BID）进行预防。</li>
        <li style="margin-bottom: 12px;">皮肤光敏性管理：由于 <strong>[[PBD]]</strong> 载荷的特性，患者在治疗期间应采取严格防晒措施，避免紫外线引发的皮肤红肿。</li>
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            <li style="margin-bottom: 8px;"><strong>[[CD19]]</strong>：B 细胞恶性肿瘤最广泛的免疫靶点。</li>
            <li style="margin-bottom: 8px;"><strong>[[PBD]]</strong> 二聚体：诱导 DNA 跨链共价交联的强效 <strong>[[ADC]]</strong> 毒素载荷。</li>
            <li style="margin-bottom: 8px;"><strong>[[DLBCL]]</strong>：弥漫大 B 细胞淋巴瘤，该药的核心适应症。</li>
            <li style="margin-bottom: 8px;"><strong>[[ADC Therapeutics]]</strong>：专注于 <strong>[[PBD]]</strong> 平台研发的创新生物制药公司。</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] Caimi PF, et al. (2021). Loncastuximab tesirine in patients with relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. <strong>[[The Lancet Oncology]]</strong>.
            <br><span style="color: #475569;">[权威点评]：该研究确立了其作为 <strong>[[DLBCL]]</strong> 挽救治疗的核心价值。</span>
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            [2] Kahl BS, et al. (2022). Loncastuximab Tesirine: A New Treatment Paradigm for B-Cell Lymphomas. <strong>[[Blood Reviews]]</strong>.[Academic Review]
            <br><span style="color: #475569;">[学术点评]：解析了 <strong>[[PBD]]</strong> 载荷在克服传统化疗耐药方面的分子学优势。</span>
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            Loncastuximab (Zynlonta) 诊疗生态 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; 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>[[CD19]]</strong>•<strong>[[PBD]]</strong>•<strong>[[DNA交联]]</strong>•<strong>[[IgG1]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">同类竞品</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[Polatuzumab Vedotin]]</strong>•<strong>[[Tafasitamab]]</strong>•<strong>[[Axi-cel]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关键实体</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[ADC Therapeutics]]</strong>•<strong>[[FDA]]</strong>•<strong>[[NCCN指南]]</strong>•<strong>[[海正药业]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">前沿方向</td>
                <td style="padding: 10px 15px; color: #334155;">联合 <strong>[[利妥昔单抗]]</strong> 一线应用•针对 <strong>[[滤泡性淋巴瘤]]</strong> 扩展•降低水肿风险的剂量优化•<strong>[[CAR-T]]</strong> 进展后的序贯方案</td>
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