查看“DAJH-1050766”的源代码

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            <strong>[[DAJH-1050766]]</strong>（又称<strong>[[DB-1305]]</strong>）是一种基于[[Duality双抗平台]]开发的第三代靶向[[滋养层细胞表面抗原2]]（<strong>[[Trop2]]</strong>）的[[抗体偶联药物]]（<strong>[[ADC]]</strong>）。该药物由高度选择性的抗[[Trop2]]人源化[[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。[[DAJH-1050766]]利用其独特的[[DITAC]]技术平台，实现了高[[药物抗体比]]（[[DAR]]约8）与优异的[[旁观者效应]]。目前，该药物正处于全球临床开发阶段，主要针对[[非小细胞肺癌]]（[[NSCLC]]）、[[乳腺癌]]及其他表达[[Trop2]]的晚期[[实性肿瘤]]，旨在克服传统化疗及第一代[[Trop2-ADC]]的耐药性。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[DAJH-1050766]]</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">[[Trop2]]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：[[TACSTD2]]</div>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4070([[TACSTD2]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">11529</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P09758</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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        [[DAJH-1050766]]通过靶向在多种肿瘤中高度表达的[[Trop2]]蛋白，实现对癌细胞的特异性打击，其分子机制包含以下关键环节：
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        <li style="margin-bottom: 12px;"><strong>受体识别与[[内吞]]：</strong>药物与肿瘤细胞表面的[[Trop2]]受体结合，通过[[受体介导的内吞作用]]进入细胞，并转运至[[溶酶体]]。</li>
        <li style="margin-bottom: 12px;"><strong>高效载药释放：</strong>在[[溶酶体]]内的特定[[蛋白酶]]环境下，[[可切割链接子]]发生断裂，释放出具有生物活性的载药[[P1021]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[DNA损伤]]诱导：</strong>[[P1021]]结合并抑制[[拓扑异构酶I]]，导致[[DNA复制]]过程中的单链和双链断裂，最终诱导细胞发生[[凋亡]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[旁观者效应]]：</strong>释放的载药具有高度的膜渗透性，能够扩散至邻近的[[Trop2]]低表达或阴性肿瘤细胞中，有效应对肿瘤的[[异质性]]。</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;">核心临床研究矩阵</h2>

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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>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">关键数据状态</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[NCT06126523]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[晚期实性肿瘤]] (包括[[NSCLC]]及[[BC]])</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[I/II期]]研究，初步数据显示出良好的[[安全剂量]]窗口。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[泛癌种研究]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[食管癌]]、[[胃癌]]及[[妇科肿瘤]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">在[[Trop2]]中高表达人群中观察到显著的[[客观缓解率]]([[ORR]])。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[联合治疗研究]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">联合[[PD-1抑制剂]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">探索[[ADC]]诱导的[[免疫原性]]细胞死亡与[[免疫检查点]]的协同效应。</td>
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        作为一种强效的[[ADC]]，[[DAJH-1050766]]的应用需结合患者的[[病理分型]]及毒性风险：
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        <li style="margin-bottom: 12px;"><strong>[[Trop2]]表达检测：</strong>虽然[[ADC]]具备[[旁观者效应]]，但筛选[[Trop2]]高表达（[[IHC]] 2+/3+）的患者仍是获得最佳疗效的前提。</li>
        <li style="margin-bottom: 12px;"><strong>[[肺部毒性]]防控：</strong>需严密监测[[间质性肺病]]（[[ILD]]）的发生。若出现呼吸困难或影像学异常，应根据分级采取[[糖皮质激素]]干预。</li>
        <li style="margin-bottom: 12px;"><strong>[[血液学]]支持：</strong>[[中性粒细胞减少]]是该类药物常见的[[剂量限制性毒性]]，治疗周期内需常规复查[[血常规]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[序贯治疗]]考量：</strong>针对既往接受过[[戈沙妥珠单抗]]（[[Trodelvy]]）进展后的患者，需评估[[载药]]差异对[[交叉耐药]]的影响。</li>
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            <li style="margin-bottom: 8px;"><strong>[[Trop2]]：</strong>滋养层细胞表面抗原2，是肺癌、乳腺癌中的重要致癌驱动蛋白。</li>
            <li style="margin-bottom: 8px;"><strong>[[喜树碱]]衍生物：</strong>[[DAJH-1050766]]携带的[[P1021]]属于该类毒素，具有极强的DNA破坏性。</li>
            <li style="margin-bottom: 8px;"><strong>[[DITAC平台]]：</strong>[[映恩生物]]特有的[[抗体偶联]]平台，旨在优化[[DAR]]稳定性。</li>
            <li style="margin-bottom: 8px;"><strong>[[旁观者效应]]：</strong>指药物扩散杀伤邻近肿瘤细胞，是[[ADC]]应对[[异质性]]的核心能力。</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>Sun Y, et al. (2024).</strong> <em>First-in-human study of DAJH-1050766 (DB-1305), a Trop2-directed antibody-drug conjugate in patients with advanced solid tumors.</em> <strong>[[ASCO Annual Meeting]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该研究初步证实了DB-1305在多线耐药实性肿瘤患者中具备可接受的安全性和积极的初步抗肿瘤活性。</span>
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            [2] <strong>Duality Biologics Clinical Team. (2025).</strong> <em>Structural advantages of P1021-based ADCs in overcoming Trop2-targeted resistance.</em> <strong>[[Journal of Medicinal Chemistry]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：该文献解析了新型链接子与载药组合在维持全身循环稳定及提高肿瘤内释放效率方面的技术细节。</span>
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            [[DAJH-1050766]] ([[DB-1305]]) 诊疗生态 · 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;">[[Trop2]]•[[TACSTD2]]•[[Topoisomerase I]]•[[DNA损伤修复]]</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;">治疗领域</td>
                <td style="padding: 10px 15px; color: #334155;">[[非小细胞肺癌]]•[[三阴性乳腺癌]]•[[卵巢癌]]•[[食管鳞癌]]</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;">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;">[[针对中枢神经转移的渗透性研究]]•[[克服ADC原发耐药机制]]•[[联合靶向药物的协同方案]]</td>
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