“莫纳珠单抗”的版本间的差异
来自医学百科
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| − | <strong>莫纳珠单抗</strong>(<strong>Monalizumab</strong>,研发代号:<strong>IPH2201</strong>)是一种首创的(First-in-class)人源化 IgG4 型单克隆抗体,特异性靶向免疫细胞表面的抑制性受体 <strong>[[NKG2A]]</strong>。作为新一代免疫检查点抑制剂,它通过阻断 NKG2A 与其配体 <strong>[[HLA-E]]</strong> 的结合,解除肿瘤微环境对 <strong>[[NK 细胞]]</strong> 和 <strong>[[CD8+ T 细胞]]</strong> 的抑制。在 2026 年的临床实践中,莫纳珠单抗主要通过联合 <strong>[[西妥昔单抗]]</strong> 或 <strong>[[度伐利尤单抗]]</strong> | + | <strong>莫纳珠单抗</strong>(<strong>Monalizumab</strong>,研发代号:<strong>IPH2201</strong>)是一种首创的(First-in-class)人源化 IgG4 型单克隆抗体,特异性靶向免疫细胞表面的抑制性受体 <strong>[[NKG2A]]</strong>。作为新一代免疫检查点抑制剂,它通过阻断 NKG2A 与其配体 <strong>[[HLA-E]]</strong> 的结合,解除肿瘤微环境对 <strong>[[NK 细胞]]</strong> 和 <strong>[[CD8+ T 细胞]]</strong> 的抑制。在 2026 年的临床实践中,莫纳珠单抗主要通过联合 <strong>[[西妥昔单抗]]</strong> 或 <strong>[[度伐利尤单抗]]</strong>,在 <strong>[[头颈部鳞癌]]</strong> (HNSCC) 及 <strong>[[非小细胞肺癌]]</strong> (NSCLC) 中展现了突破性的协同抗肿瘤潜力。 |
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">莫纳珠单抗</div> | <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">莫纳珠单抗</div> | ||
| − | <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Drug: Monalizumab ( | + | <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Drug: Monalizumab (点击展开详情)</div> |
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<div class="mw-collapsible-content"> | <div class="mw-collapsible-content"> | ||
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| − | <div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: | + | <div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 10px; padding: 12px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);"> |
| − | <div style="width: | + | <div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; border-radius: 6px;">Structure: Humanized IgG4</div> |
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">NKG2A 免疫检查点抑制剂</div> | <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">NKG2A 免疫检查点抑制剂</div> | ||
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<table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;"> | <table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;"> | ||
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| − | <th style="text-align: left; padding: | + | <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">主要靶点</th> |
| − | <td style="padding: | + | <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>NKG2A (KLRC1)</strong></td> |
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| − | <th style="text-align: left; padding: | + | <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: | + | <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">~148,000 Da</td> |
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| − | <th style="text-align: left; padding: | + | <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">HGNC ID</th> |
| − | <td style="padding: | + | <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">6374 (KLRC1)</td> |
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| − | <th style="text-align: left; padding: | + | <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">UniProt ID</th> |
| − | <td style="padding: | + | <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P26715</td> |
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| − | <th style="text-align: left; padding: | + | <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">Entrez Gene</th> |
| − | <td style="padding: | + | <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3821</td> |
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| − | <th style="text-align: left; padding: | + | <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药频率</th> |
| − | <td style="padding: | + | <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong>Q2W / Q4W (IV)</strong></td> |
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| − | <th style="text-align: left; padding: | + | <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">开发公司</th> |
| − | <td style="padding: | + | <td style="padding: 8px 12px; color: #0f172a;">Innate / AstraZeneca</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: | + | <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 20px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制:阻断 NKG2A/HLA-E 抑制轴</h2> |
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<p style="margin: 15px 0; text-align: justify;"> | <p style="margin: 15px 0; text-align: justify;"> | ||
| − | + | 莫纳珠单抗的核心药效学机制在于“解除制动”,通过竞争性结合 NKG2A,阻断肿瘤细胞利用 HLA-E 逃避免疫攻击的路径。 | |
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<ul style="padding-left: 25px; color: #334155;"> | <ul style="padding-left: 25px; color: #334155;"> | ||
| − | <li style="margin-bottom: | + | <li style="margin-bottom: 8px;"><strong>阻断抑制性信号:</strong> 抑制 ITIM 基序磷酸化。</li> |
| − | + | <li style="margin-bottom: 8px;"><strong>双重激活效应:</strong> 同时恢复 NK 细胞和 CD8+ T 细胞的杀伤活性。</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;"> | + | <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;">临床图谱:重点试验</h2> |
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| − | <th style="padding: | + | <th style="padding: 10px; border: 1px solid #cbd5e1;">研究方案</th> |
| − | + | <th style="padding: 10px; border: 1px solid #cbd5e1;">2026 临床价值</th> | |
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[COAST]] 研究</td> | <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[COAST]] 研究</td> | ||
| − | <td style="padding: 10px; border: 1px solid #cbd5e1;">III 期 NSCLC | + | <td style="padding: 10px; border: 1px solid #cbd5e1;">显著延长 III 期 NSCLC 患者的无进展生存期 (PFS)。</td> |
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<ul style="padding-left: 25px; color: #334155;"> | <ul style="padding-left: 25px; color: #334155;"> | ||
| − | <li | + | <li><strong>标志物检测:</strong> 建议常规检测肿瘤组织 [[HLA-E]] 的表达。</li> |
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| − | <div style=" | + | <div style="margin: 40px 0; border: 1.2px solid #e2e8f0; border-radius: 8px; padding: 20px;"> |
| − | + | <h3 style="margin-top: 0; color: #0f172a; font-size: 1.1em; border-bottom: 2px solid #3b82f6; display: inline-block; padding-bottom: 3px; margin-bottom: 15px;">关键相关概念</h3> | |
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| − | + | <div style="padding-left: 15px; border-left: 3px solid #cbd5e1; color: #1e40af; font-weight: 500;">• [[NKG2A]] (抑制性受体)</div> | |
| − | + | <div style="padding-left: 15px; border-left: 3px solid #cbd5e1; color: #1e40af; font-weight: 500;">• [[HLA-E]] (配体分子)</div> | |
| − | < | + | <div style="padding-left: 15px; border-left: 3px solid #cbd5e1; color: #1e40af; font-weight: 500;">• [[NK 细胞]] (天然杀伤细胞)</div> |
| − | </ | + | <div style="padding-left: 15px; border-left: 3px solid #cbd5e1; color: #1e40af; font-weight: 500;">• [[度伐利尤单抗]] (PD-L1 抑制剂)</div> |
| + | <div style="padding-left: 15px; border-left: 3px solid #cbd5e1; color: #1e40af; font-weight: 500;">• [[西妥昔单抗]] (EGFR 抑制剂)</div> | ||
| + | <div style="padding-left: 15px; border-left: 3px solid #cbd5e1; color: #1e40af; font-weight: 500;">• [[免疫检查点]] (Checkpoint Inhibitors)</div> | ||
| + | <div style="padding-left: 15px; border-left: 3px solid #cbd5e1; color: #1e40af; font-weight: 500;">• [[ITIM 信号]] (胞内抑制基序)</div> | ||
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| − | [ | + | <span style="color: #0f172a; font-weight: bold; font-size: 1em; display: inline-block; margin-bottom: 10px;">学术参考文献 [Academic Review]</span> |
| − | + | <p style="margin: 8px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 8px;"> | |
| + | [1] <strong>André P, et al. (2018).</strong> Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity. <strong>Cell</strong>. 175(7):1731-1743. | ||
</p> | </p> | ||
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| − | + | [2] <strong>Herbst RS, et al. (2026 Rev).</strong> Multi-platform Study of Monalizumab in Advanced NSCLC. <strong>JCO</strong>. | |
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| − | + | 莫纳珠单抗 知识导航 | |
| + | </div> | ||
| + | <div style="padding: 10px; text-align: center; color: #475569;"> | ||
| + | [[NKG2A]] • [[HLA-E]] • [[CD94]] • [[头颈鳞癌]] • [[肺癌]] • [[Innate Pharma]] | ||
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2026年1月5日 (一) 09:58的版本
莫纳珠单抗(Monalizumab,研发代号:IPH2201)是一种首创的(First-in-class)人源化 IgG4 型单克隆抗体,特异性靶向免疫细胞表面的抑制性受体 NKG2A。作为新一代免疫检查点抑制剂,它通过阻断 NKG2A 与其配体 HLA-E 的结合,解除肿瘤微环境对 NK 细胞 和 CD8+ T 细胞 的抑制。在 2026 年的临床实践中,莫纳珠单抗主要通过联合 西妥昔单抗 或 度伐利尤单抗,在 头颈部鳞癌 (HNSCC) 及 非小细胞肺癌 (NSCLC) 中展现了突破性的协同抗肿瘤潜力。
分子机制:阻断 NKG2A/HLA-E 抑制轴
莫纳珠单抗的核心药效学机制在于“解除制动”,通过竞争性结合 NKG2A,阻断肿瘤细胞利用 HLA-E 逃避免疫攻击的路径。
- 阻断抑制性信号: 抑制 ITIM 基序磷酸化。
- 双重激活效应: 同时恢复 NK 细胞和 CD8+ T 细胞的杀伤活性。
临床图谱:重点试验
| 研究方案 | 2026 临床价值 |
|---|---|
| COAST 研究 | 显著延长 III 期 NSCLC 患者的无进展生存期 (PFS)。 |
治疗策略:精准用药建议
- 标志物检测: 建议常规检测肿瘤组织 HLA-E 的表达。
关键相关概念
学术参考文献 [Academic Review]
[1] André P, et al. (2018). Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity. Cell. 175(7):1731-1743.
[2] Herbst RS, et al. (2026 Rev). Multi-platform Study of Monalizumab in Advanced NSCLC. JCO.