查看“Axi-cel”的源代码

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            <strong>[[Axi-cel]]</strong>（通用名为 <strong>[[阿昔亮赛]]</strong> 或 <strong>[[阿基仑赛]]</strong>），商品名为 <strong>[[Yescarta]]</strong>，研发代码为 <strong>[[KTE-C19]]</strong>，是由 <strong>[[吉利德]]</strong>（<strong>[[Gilead]]</strong>）旗下 <strong>[[Kite Pharma]]</strong> 开发的一种针对 <strong>[[CD19]]</strong> 靶点的自体 <strong>[[CAR-T细胞疗法]]</strong>。该产品通过慢病毒载体将含有 FMC63 单链抗体片段及 <strong>[[CD28]]</strong> 共刺激结构域的嵌合抗原受体基因导入患者自身的 T 细胞。作为全球首个获批用于治疗 <strong>[[复发或难治性大B细胞淋巴瘤]]</strong>（<strong>[[R/R LBCL]]</strong>）的 <strong>[[CAR-T]]</strong> 产品，<strong>[[Axi-cel]]</strong> 在二线及后线挽救治疗中展现了卓越的缩瘤活性与长期生存获益。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">Yescarta (阿昔亮赛)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Axicabtagene Ciloleucel · KTE-C19</div>
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                     <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;">Yescarta: CD19-directed autologous CAR-T cell construct</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px;">核心靶标：<strong>[[CD19]]</strong></div>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%; font-weight: normal;"><strong>[[Entrez]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">930 (<strong>[[CD19]]</strong>)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;"><strong>[[HGNC]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1633</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;"><strong>[[UniProt]]</strong></th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P15391</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">共刺激域</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;"><strong>[[CD28]]</strong></td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">给药途径</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">静脉回输 (IV)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">研发厂家</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;"><strong>[[Kite]]</strong> / <strong>[[吉利德]]</strong></td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; font-weight: normal;">审批状态</th>
                    <td style="padding: 12px; color: #16a34a;">NMPA/FDA 已批准</td>
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        <strong>[[Axi-cel]]</strong> 的核心设计通过遗传工程手段赋予 T 细胞精准打击 B 细胞肿瘤的能力：
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        <li style="margin-bottom: 12px;">抗原识别：利用高亲和力的 FMC63 单链抗体片段（scFv）识别肿瘤细胞表面的 <strong>[[CD19]]</strong> 蛋白，该靶点广泛表达于 <strong>[[B细胞淋巴瘤]]</strong> 细胞表面。</li>
        <li style="margin-bottom: 12px;">快速激活动力学：采用 <strong>[[CD28]]</strong> 作为共刺激结构域。相比 4-1BB 结构域，<strong>[[CD28]]</strong> 能诱导更快速、更强劲的 T 细胞扩增与信号转导，使细胞在短期内释放大量效应细胞因子。</li>
        <li style="margin-bottom: 12px;">溶细胞作用：活化的 CAR-T 细胞通过释放颗粒酶和 <strong>[[穿孔素]]</strong> 直接裂解靶细胞，并介导后续的免疫级联反应。</li>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%; font-weight: bold;">研究名称</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569; font-weight: bold;">适应症/患者群</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[ZUMA-1]]</strong></td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">三线及后线治疗的 <strong>[[R/R DLBCL]]</strong>。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">客观缓解率 (ORR) 达 83%；五年总生存 (OS) 率表现出治愈潜力。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[ZUMA-7]]</strong></td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">二线治疗 <strong>[[弥漫大B细胞淋巴瘤]]</strong> (对比标准二线化疗+移植)。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">显著延长无进展生存期 (PFS)；确立了 <strong>[[Axi-cel]]</strong> 在高危复发患者中的二线地位。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>[[ZUMA-5]]</strong></td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">复发或难治性 <strong>[[滤泡性淋巴瘤]]</strong> (FL)。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">在惰性淋巴瘤中实现了极高的完全缓解率 (CR)。</td>
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        <strong>[[Axi-cel]]</strong> 的临床应用强调围手术期的精细化管理以平衡疗效与风险：
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        <li style="margin-bottom: 12px;">清淋预处理：在回输前 3-5 天给予氟达拉滨 + 环磷酰胺化疗。该步骤旨在清除内源性淋巴细胞，诱导 <strong>[[IL-15]]</strong> 等因子水平升高，为 CAR-T 细胞的爆发式增殖清除障碍。</li>
        <li style="margin-bottom: 12px;">CRS 早期监测：由于 <strong>[[CD28]]</strong> 结构域起效快，<strong>[[细胞因子释放综合征]]</strong>（CRS）通常在回输后前 3 天内发生。临床需严密监测体温和氧合状态。</li>
        <li style="margin-bottom: 12px;">神经毒性防控：<strong>[[神经毒性]]</strong>（ICANS）是 <strong>[[Axi-cel]]</strong> 常见的副作用之一。若出现书写困难或意识模糊，需及时按指南应用 <strong>[[托珠单抗]]</strong> 或糖皮质激素。</li>
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            <li style="margin-bottom: 8px;"><strong>[[CD19]]</strong>：B 细胞恶性肿瘤最广谱的表面靶标，<strong>[[Axi-cel]]</strong> 的导航定位点。</li>
            <li style="margin-bottom: 8px;"><strong>[[CD28]]</strong>：决定 <strong>[[CAR-T]]</strong> 细胞体内激活速率和细胞因子释放强度的共刺激信号。</li>
            <li style="margin-bottom: 8px;"><strong>[[DLBCL]]</strong>：弥漫大 B 细胞淋巴瘤，<strong>[[Axi-cel]]</strong> 最核心的临床应用场景。</li>
            <li style="margin-bottom: 8px;"><strong>[[中性粒细胞减少]]</strong>：回输后常见的血液学毒性，需进行严密的抗感染预防。</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] Locke FL, et al. (2017). Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a pivotal trial. <strong>[[The New England Journal of Medicine]]</strong>.
            <br><span style="color: #475569;">[权威点评]：该研究确立了 <strong>[[Axi-cel]]</strong> 在淋巴瘤末线治疗中的里程碑地位。</span>
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            [2] Westin J, et al. (2023). Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma (ZUMA-7). <strong>[[The New England Journal of Medicine]]</strong>.[Academic Review]
            <br><span style="color: #475569;">[学术点评]：解析了 <strong>[[Axi-cel]]</strong> 在二线治疗中优于标准自体移植（ASCT）的生存数据。</span>
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            Axi-cel (Yescarta) 诊疗生态 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[CD19]]</strong>•<strong>[[CD28]]</strong>•<strong>[[CD3z]]</strong>•<strong>[[IL-6]]</strong>•<strong>[[IFN-gamma]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">同类产品</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[布瑞希奥仑赛]]</strong> (Tecartus)•<strong>[[替雷利珠单抗]]</strong> (Kymriah)•<strong>[[瑞基奥仑赛]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略实体</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[吉利德]]</strong>•<strong>[[Kite Pharma]]</strong>•<strong>[[FDA]]</strong>•<strong>[[NMPA]]</strong>•<strong>[[NCCN]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">前沿探索</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[针对高肿瘤负荷减瘤方案]]</strong>•针对 <strong>[[中枢神经系统淋巴瘤]]</strong> 应用•<strong>[[快速生产工艺]]</strong> (7天制备)•二线维持方案</td>
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