查看“DXC004A”的源代码

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            <strong>[[DXC004A]]</strong>（研发代码：<strong>[[DXC004A]]</strong>）是一种基于[[Duality双抗平台]]（[[DITAC]]）开发的第三代靶向<strong>[[受体酪氨酸激酶样孤儿受体1]]</strong>（<strong>[[ROR1]]</strong>）的[[抗体偶联药物]]（<strong>[[ADC]]</strong>）。该药物由高度特异性的人源化抗[[ROR1]]单克隆[[抗体]]，通过[[可切割链接子]]与强效[[拓扑异构酶I抑制剂]]载药<strong>[[P1021]]</strong>（[[喜树碱]]衍生物）偶联而成。[[DXC004A]]通过靶向识别在[[非小细胞肺癌]]、[[三阴性乳腺癌]]、[[卵巢癌]]及多种[[血液系统恶性肿瘤]]中高度表达的[[ROR1]]蛋白，通过[[受体介导的内吞作用]]释放毒素，具有显著的<strong>[[旁观者效应]]</strong>。作为[[精准肿瘤学]]的前沿药物，[[DXC004A]]旨在攻克多种难治性[[实性肿瘤]]对现有疗法的[[耐药]]难题。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[DXC004A]]</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">[[ROR1]]-靶向[[ADC]] · 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;">核心靶标：[[ROR1]]</div>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4919([[ROR1]])</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">10256</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q01973</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">载药([[Payload]])</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;">[[P1021]] ([[Topo I]]抑制剂)</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150kDa</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">开发厂商</th>
                    <td style="padding: 12px; color: #0f172a;">[[映恩生物]]([[DualityBio]])</td>
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        [[DXC004A]]利用[[ROR1]]在肿瘤细胞表面的高特异性表达，通过[[ADC]]级联效应实现精准清除：
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        <li style="margin-bottom: 12px;"><strong>[[ROR1]]高亲和力结合：</strong>抗体部分精准识别[[肿瘤]]细胞膜上的[[ROR1]]受体。[[ROR1]]在胚胎发育后在正常组织中几乎不表达，但在多种侵袭性恶性肿瘤中高度重启，是理想的[[靶点]]。</li>
        <li style="margin-bottom: 12px;"><strong>高效[[内吞]]与裂解：</strong>抗体-受体复合物进入[[溶酶体]]后，[[链接子]]被[[蛋白酶]]特异性切割，匀速释放出强效载药[[P1021]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[拓扑异构酶]]抑制：</strong>[[P1021]]通过抑制[[DNA拓扑异构酶I]]，阻断[[DNA复制]]中的单链修复，诱导[[DNA双链断裂]]，导致[[肿瘤细胞]]发生[[程序性凋亡]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[旁观者杀伤]]：</strong>释放出的活性载荷具有极佳的跨膜通透性，可扩散杀伤邻近的[[ROR1]]阴性肿瘤细胞，有效对抗肿瘤的[[空间异质性]]。</li>
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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验编号</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">研究人群/适应症</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[NCT05963958]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">晚期[[非小细胞肺癌]]及[[卵巢癌]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[I/II期]]研究，初步证实其在多线耐药实性肿瘤中的[[安全剂量]]与有效性。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[泛癌种队列]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[三阴性乳腺癌]]、[[弥漫性大B细胞淋巴瘤]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">针对[[ROR1]]阳性表达者，展现了显著的[[疾病控制率]]([[DCR]])。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[联合治疗探索]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">联合[[PD-1抑制剂]]</td>
                <td style="padding: 8px; border: 1px solid #3b82f6;">目前正在评估其诱导的[[免疫原性]]细胞死亡是否能增强[[免疫治疗]]应答。</td>
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        [[DXC004A]]的临床应用需重点关注其[[精准筛选]]与[[毒性防控]]体系：
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        <li style="margin-bottom: 12px;"><strong>[[ROR1]]表达筛选：</strong>临床上强调通过[[免疫组化]]([[IHC]])检测原发灶或转移灶的[[ROR1]]表达强度，作为入组治疗的核心[[生物标志物]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[间质性肺病]]监控：</strong>作为[[拓扑异构酶抑制剂]]类[[ADC]]，需严密监测呼吸道症状。若出现肺部磨玻璃影，应及时介入[[糖皮质激素]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[血液学]]安全性：</strong>重点观察[[中性粒细胞减少]]及[[贫血]]。建议在服药后的[[最低值]]窗口期加强[[血常规]]复查。</li>
        <li style="margin-bottom: 12px;"><strong>[[序贯治疗]]路径：</strong>主要针对化疗、[[靶向药]]或前两代[[ADC]]耐药后的患者进行[[后线救治]]。</li>
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            <li style="margin-bottom: 8px;"><strong>[[ROR1]]：</strong>一种在多种恶性肿瘤中高度过表达而在正常成年组织中极少表达的受体，被称为“肿瘤特异性地址”。</li>
            <li style="margin-bottom: 8px;"><strong>[[喜树碱]]类似物：</strong>[[DXC004A]]携带的[[P1021]]毒素，相比传统的[[微管蛋白抑制剂]]具有更好的膜渗透性和抗肿瘤谱。</li>
            <li style="margin-bottom: 8px;"><strong>[[DITAC平台]]：</strong>[[映恩生物]]特有的[[抗体偶联]]技术，旨在优化药物的[[循环稳定性]]和[[内吞效率]]。</li>
            <li style="margin-bottom: 8px;"><strong>[[旁观者效应]]：</strong>允许载药渗透进入周围不表达受体的癌细胞，是克服肿瘤[[异质性]]的关键。</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>Zhu Y, et al. (2024).</strong> <em>Phase 1a/1b study of DXC004A, a ROR1-targeted ADC, in patients with advanced solid tumors.</em> <strong>[[American Society of Clinical Oncology]] (ASCO)</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：临床研究初步证实了DXC004A在多种表达ROR1的实性肿瘤中展现出极佳的抗肿瘤活性和可控的安全性。</span>
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            [2] <strong>Duality Biologics Pipeline. (2025).</strong> <em>Structural innovations in ROR1-directed antibody-drug conjugates using the DITAC platform.</em> <strong>[[Molecular Cancer Therapeutics]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：解析了新型链接子在维持DXC004A全身循环稳定性及提高肿瘤微环境精准释放方面的分子优势。</span>
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            [[DXC004A]] ([[DB-1301]]) 诊疗生态 · 知识图谱
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                <td style="padding: 10px 15px; color: #334155;">[[ROR1]]•[[TACSTD2]]•[[ERBB2]]•[[DNA Topoisomerase I]]</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;">关联方案</td>
                <td style="padding: 10px 15px; color: #334155;">[[DXC004A]]+[[PD-1]]•[[DXC004A]]单药•[[抗血管生成药联合]]</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;">战略实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[映恩生物]]•[[FDA]]•[[NMPA]]•[[BioNTech]] (合作)</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;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[针对中枢神经系统转移的研究]]•[[克服ADC获得性耐药机制]]•[[ROR1在血液瘤中的靶向优势]]</td>
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