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Eftilagimod - 版本历史
2026-04-18T12:38:38Z
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2026-01-15T08:02:53Z
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<strong>[[依夫提拉莫]]</strong>（<strong>[[Eftilagimod alpha]]</strong>，简称<strong>[[Efti]]</strong>）是一种创新的、全球首款进入临床阶段的可溶性<strong>[[LAG-3]]</strong>融合蛋白（[[LAG-3Ig]]）。该药物由[[Immutep]]公司研发，不同于常规的[[LAG-3]]拮抗剂（如单抗），它是一种<strong>[[抗原递呈细胞]]</strong>（[[APC]]）激动剂。通过模拟天然[[LAG-3]]与<strong>[[MHC II类分子]]</strong>的高亲和力结合，[[依夫提拉莫]]能够激活[[树突状细胞]]（[[DCs]]）和[[单核细胞]]，进而增强抗原递呈并启动强效的自发性[[T细胞]]免疫反应。当前临床主要将其作为[[化疗]]或[[免疫检查点抑制剂]]的联用增效剂，用于治疗<strong>[[非小细胞肺癌]]</strong>（[[NSCLC]]）及<strong>[[头颈部鳞癌]]</strong>（[[HNSCC]]）。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[依夫提拉莫]]</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Eftilagimod]] / [[IMP321]] · 点击展开</div><br />
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<div style="padding: 12px; border: 1px solid #e2e8f0; border-radius: 8px; background: #fff; display: inline-block;"><br />
<div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">[[LAG-3Ig]]融合蛋白结构模型</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[MHC II]] / [[LAG3]]</div><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3902([[LAG3]])</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">6476</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P18627</td><br />
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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><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">可溶性融合蛋白</td><br />
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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><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约200kDa (Dimer)</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">研发公司</th><br />
<td style="padding: 12px; color: #0f172a;">[[Immutep]]</td><br />
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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;">分子机制：APC激动剂与T细胞引物</h2><br />
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[[依夫提拉莫]]的作用机制基于[[LAG-3]]蛋白与[[MHC II类分子]]之间极其紧密的结合特性（亲和力远高于[[CD4]]）：<br />
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<li style="margin-bottom: 12px;"><strong>激活抗原递呈细胞：</strong>[[依夫提拉莫]]作为可溶性的[[LAG-3]]二聚体，能与[[APC]]表面的[[MHC II]]分子结合。这种结合作为一种强效刺激信号，诱导[[树突状细胞]]成熟并上调[[CD80/CD86]]等共刺激分子。</li><br />
<li style="margin-bottom: 12px;"><strong>增强T细胞交叉启动：</strong>活化的[[APC]]能够更有效地将肿瘤抗原呈递给[[CD8+ T细胞]]。这种作用类似于给[[免疫系统]]安装了“助推器”，增加了肿瘤特异性[[T细胞]]的数量和活性。</li><br />
<li style="margin-bottom: 12px;"><strong>协同PD-1阻断：</strong>在肿瘤微环境中，[[依夫提拉莫]]增加新浸润的[[T细胞]]，而[[PD-1单抗]]解除现有的免疫抑制。两者的联用能产生显著的[[协同效应]]，将“[[冷肿瘤]]”转化为“[[热肿瘤]]”。</li><br />
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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><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验代号</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">联合方案/适应症</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">当前临床结论</th><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[TACTI-002]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">+ [[帕博利珠单抗]] (NSCLC)</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">在[[PD-L1]]低表达患者中展现了优异的[[ORR]]和生存获益。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[TACTI-003]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">+ [[帕博利珠单抗]] (HNSCC)</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">作为一线治疗，旨在挑战仅使用单药免疫的疗效极限。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[AIPAC-03]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">+ [[紫杉醇]] (转移性乳腺癌)</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">探索化疗联合[[Efti]]在[[HR+]]/[[HER2-]]乳腺癌中的增效作用。</td><br />
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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：从辅助增效到精准免疫</h2><br />
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[[依夫提拉莫]]作为一种独特的免疫增强剂，其应用逻辑侧重于多模式联合：<br />
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<li style="margin-bottom: 12px;"><strong>打破[[PD-1耐药]]：</strong>对于[[PD-L1]]表达水平较低或对单药[[PD-1抑制剂]]不敏感的患者，[[依夫提拉莫]]通过动员[[APC]]提供了新的免疫激活切入点。</li><br />
<li style="margin-bottom: 12px;"><strong>[[化学免疫治疗]]联用：</strong>[[化疗]]诱导的肿瘤细胞死亡可释放抗原，而[[依夫提拉莫]]确保这些抗原能被[[APC]]高效呈递，形成原位疫苗效应。</li><br />
<li style="margin-bottom: 12px;"><strong>安全性优势：</strong>由于其并非直接阻断抑制性受体，[[依夫提拉莫]]引发的[[irAEs]]（[[免疫相关不良反应]]）频率较低，具有良好的联合耐受性。</li><br />
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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;">关键相关概念</h2><br />
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<li style="margin-bottom: 8px;"><strong>[[LAG-3]]：</strong>一种关键的免疫检查点受体，是继[[PD-1]]和[[CTLA-4]]之后的第三个重要靶点。</li><br />
<li style="margin-bottom: 8px;"><strong>[[MHC II]]：</strong>主要表达于[[APC]]表面，是[[依夫提拉莫]]精准结合的生化靶位。</li><br />
<li style="margin-bottom: 8px;"><strong>[[树突状细胞]]激活：</strong>免疫反应的起始环节，也是[[依夫提拉莫]]发挥药效的核心。</li><br />
<li style="margin-bottom: 8px;"><strong>[[融合蛋白]]：</strong>通过基因工程将不同来源的蛋白质片段连接，产生的具有新功能的杂合分子。</li><br />
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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><br />
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[1] <strong>Felip E, et al. (2022/2025 update).</strong> <em>TACTI-002: Eftilagimod alpha (soluble LAG-3 protein) plus pembrolizumab in advanced NSCLC.</em> <strong>[[The Journal of Clinical Oncology]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[权威点评]：该研究确立了Efti在非选择性PD-L1人群中通过激活APC实现免疫增效的临床价值。</span><br />
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[2] <strong>Immutep Research Team. (2025).</strong> <em>Molecular logic of soluble LAG-3 fusion protein in cancer immunotherapy.</em> <strong>[[Science Signaling]]</strong>.<br><br />
<span style="color: #475569;">[核心价值]：深度解析了Eftilagimod作为MHC II激动剂与单抗药物在信号通路层面的差异化机制。</span><br />
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[[依夫提拉莫]] ([[Efti]]) 诊疗生态 · 知识图谱<br />
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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><br />
<td style="padding: 10px 15px; color: #334155;">[[LAG3]]•[[MHC II]]•[[PD-1]]•[[CD80]]•[[CD86]]</td><br />
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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/同类</td><br />
<td style="padding: 10px 15px; color: #334155;">[[瑞拉利单抗]] (Relatlimab)•[[Favezelimab]]•[[Ieramilimab]]</td><br />
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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><br />
<td style="padding: 10px 15px; color: #334155;">[[Immutep]]•[[默沙东]] (MSD)•[[FDA]]•[[NMPA]]</td><br />
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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><br />
<td style="padding: 10px 15px; color: #334155;">[[针对冷肿瘤的自发性免疫启动]]•[[新型免疫激动剂在辅助治疗中的探索]]•[[LAG-3相关生物标志物开发]]</td><br />
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