查看“法列图珠单抗”的源代码

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            <strong>[[法列图珠单抗]]</strong>（<strong>[[Farletuzumab]]</strong>，研发代码：<strong>[[MORAb-003]]</strong>）是一种重组人源化单克隆抗体，特异性靶向<strong>[[叶酸受体α]]</strong>（[[FRα]]，由[[FOLR1]]基因编码）。作为一种[[IgG1]]型抗体，[[法列图珠单抗]]通过与[[FRα]]高亲和力结合，旨在通过[[抗体依赖性细胞介导的细胞毒作用]]（[[ADCC]]）和[[补体依赖的细胞毒作用]]（[[CDC]]）清除高表达该受体的肿瘤细胞。临床上，它曾被广泛探索用于治疗<strong>[[卵巢癌]]</strong>及某些类型的[[非小细胞肺癌]]。尽管早期单药试验显示出良好的耐受性，但目前的研究重点已转向其[[抗体偶联药物]]（[[ADC]]）形式的演进，以克服传统单抗在晚期实体瘤中应答率有限的挑战。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[法列图珠单抗]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Farletuzumab]] / [[MORAb-003]] · 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：[[FOLR1]] (FRα)</div>
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                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2348([[FOLR1]])</td>
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                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P15328</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类型</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[人源化单克隆抗体]]</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约145kDa</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药方式</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[静脉滴注]]</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">开发厂商</th>
                    <td style="padding: 12px; color: #0f172a;">[[Eisai]] (卫材)</td>
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        [[法列图珠单抗]]的作用机制复杂，主要通过免疫应答和胞内信号干扰实现抑瘤效果：
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        <li style="margin-bottom: 12px;"><strong>免疫效应募集：</strong>作为[[IgG1]]抗体，其[[Fc段]]能结合[[自然杀伤细胞]]（[[NK细胞]]）表面的[[CD16]]受体，诱导[[ADCC]]；同时激活补体系统引发[[CDC]]，通过形成[[膜攻击复合物]]（MAC）直接裂解肿瘤细胞。</li>
        <li style="margin-bottom: 12px;"><strong>信号通路抑制：</strong>[[法列图珠单抗]]与[[FRα]]结合后，可干扰受体与下游[[LYN激酶]]的互作，从而抑制促进细胞存活和增殖的信号传导。</li>
        <li style="margin-bottom: 12px;"><strong>自噬诱导与凋亡：</strong>部分研究表明，该药可能通过阻断[[叶酸]]摄取的部分非经典途径（如非转运依赖型信号），诱导肿瘤细胞进入[[自噬]]或[[凋亡]]程序。</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;">临床评价矩阵：从单抗到ADC的演进</h2>

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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">临床试验代号</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">研究设计/受试人群</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">关键结论与趋势</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[MORAb-003-003]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">III期：联合铂类化疗治疗铂敏感复发性卵巢癌。</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">全人群未达到 [[PFS]] 主要终点，但在低 [[CA-125]] 水平亚组中显示获益趋势。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[MORAb-202]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[Farletuzumab Ecteribulin]]：法列图珠单抗偶联[[艾立布林]]。</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">新一代 [[ADC]] 形式，显著提升了对低/中表达 [[FRα]] 肿瘤的杀伤力。</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;">诊疗策略：基于受体表达的精准分层</h2>
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        [[法列图珠单抗]]及其衍生药物的应用高度依赖于对病灶分子特性的深度识别：
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        <li style="margin-bottom: 12px;"><strong>[[FRα]]表达量筛选：</strong>临床推荐使用[[免疫组化]]（[[IHC]]）评估肿瘤组织的受体表达强度（[[PS]]得分）。高表达人群（如得分≥75%）是该靶向方案的最优受试群体。</li>
        <li style="margin-bottom: 12px;"><strong>[[生物标志物]]联合监测：</strong>[[CA-125]]水平与该药的应答强度存在负相关性，反映了肿瘤负荷及循环抗体捕获对药效的影响。</li>
        <li style="margin-bottom: 12px;"><strong>克服免疫逃逸：</strong>由于单抗可能引发[[调节性T细胞]]（Tregs）募集，目前的策略倾向于将其与[[免疫检查点抑制剂]]或局部化疗序贯联用。</li>
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            <li style="margin-bottom: 8px;"><strong>[[FOLR1]]：</strong>编码[[叶酸受体α]]的基因，在正常上皮组织表达极低，在卵巢癌中广泛高表达。</li>
            <li style="margin-bottom: 8px;"><strong>[[ADCC]]：</strong>抗体介导的靶细胞裂解，是[[法列图珠单抗]]发挥药效的核心免疫逻辑。</li>
            <li style="margin-bottom: 8px;"><strong>[[艾立布林]] (Ecteribulin)：</strong>常作为法列图珠单抗 [[ADC]] 演进版本的强效载荷。</li>
            <li style="margin-bottom: 8px;"><strong>[[Mirvetuximab Soravtansine]]：</strong>同一靶点的竞争性 [[ADC]] 药物，已获得临床应用批准。</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>Vergote I, et al. (2016).</strong> <em>Farletuzumab in combination with platinum-based chemotherapy in patients with platinum-sensitive ovarian cancer: a randomized, double-blind, placebo-controlled, phase III study.</em> <strong>[[Journal of Clinical Oncology]]</strong>. 34(11):1187-1194.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该项III期研究虽然未达整体生存终点，但为后续FRα靶点的亚群筛选及ADC药物开发提供了关键数据基础。</span>
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            [2] <strong>Konner JA, et al. (2010).</strong> <em>Farletuzumab, a humanized monoclonal antibody against folate receptor alpha, in epithelial ovarian cancer: a phase I study.</em> <strong>[[Clinical Cancer Research]]</strong>. 16(21):5288-5295.<br>
            <span style="color: #475569;">[核心价值]：首次在临床中验证了法列图珠单抗在人体内的安全性和靶向FRα的选择性。</span>
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            [[法列图珠单抗]] 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;">[[FOLR1]]•[[LYN]]•[[Folic Acid]]•[[CA-125]]</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;">演进版本</td>
                <td style="padding: 10px 15px; color: #334155;">[[Farletuzumab Ecteribulin]] ([[MORAb-202]])</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;">[[Eisai]] (卫材)•[[Bristol-Myers Squibb]] (BMS)•[[FDA]]</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;">[[ADC载荷优化]]•[[FRα低表达人群获益]]•[[法列图珠单抗与PARP抑制剂协同]]</td>
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