https://www.yiliao.com/index.php?action=history&feed=atom&title=%E9%98%BF%E5%8D%A1%E5%B8%95%E5%A1%94%E9%9F%A6
阿卡帕塔韦 - 版本历史
2026-04-19T03:16:57Z
本wiki的该页面的版本历史
MediaWiki 1.35.1
https://www.yiliao.com/index.php?title=%E9%98%BF%E5%8D%A1%E5%B8%95%E5%A1%94%E9%9F%A6&diff=316161&oldid=prev
103.220.218.7：建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面
2026-02-02T12:38:46Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
<br />
<div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;"><br />
<p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;"><br />
<strong>[[阿卡帕塔韦]]([[Acapatamab]])</strong>，研发代号<strong>[[AMG 160]]</strong>，是一种基于<strong>[[HLE-BiTE]]</strong>（半衰期延长型双特异性T细胞衔接器）技术的靶向治疗药物，主要用于<strong>[[转移性去势抵抗性前列腺癌]]([[mCRPC]])</strong>的治疗探索。它通过同时结合肿瘤细胞表面的<strong>[[PSMA]]</strong>（前列腺特异性膜抗原）和T细胞表面的<strong>[[CD3]]</strong>，将患者自身的T细胞重定向至前列腺癌细胞进行杀伤。<br />
<br>作为首批进入临床的 HLE-BiTE 分子，[[阿卡帕塔韦]]验证了“每两周给药一次”在实体瘤免疫治疗中的可行性，并为后续更高效的药物（如靶向 [[STEAP1]] 的 [[Xaluritamig]]）奠定了关键的临床转化基础。<br />
</p><br />
</div><br />
<br />
<div class="medical-infobox mw-collapsible mw-collapsed" style="width: 100%; max-width: 320px; margin: 0 auto 35px auto; border: 1.2px solid #bae6fd; border-radius: 12px; background-color: #ffffff; box-shadow: 0 8px 20px rgba(0,0,0,0.05); overflow: hidden;"><br />
<br />
<div style="padding: 15px; color: #1e40af; background: linear-gradient(135deg, #e0f2fe 0%, #bae6fd 100%); text-align: center; cursor: pointer;"><br />
<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">阿卡帕塔韦</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Acapatamab (AMG 160) · 点击展开</div><br />
</div><br />
<br />
<div class="mw-collapsible-content"><br />
<div style="padding: 25px; text-align: center; background-color: #f8fafc;"><br />
<div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 12px; padding: 20px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);"><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;">[Image: Structure of Acapatamab binding PSMA and CD3]</div><br />
</div><br />
<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">靶点：PSMA x CD3 双特异性</div><br />
</div><br />
<br />
<table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;"><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[CAS]]号</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2250169-07-2</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量(MW)</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">~104 kDa</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">结构特征</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">单链 scFv-Fc 融合</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发厂家</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[Amgen]] (安进)</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药方式</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong>IV, Q2W</strong> (短时输注)</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">临床状态</th><br />
<td style="padding: 12px; color: #b91c1c;">策略调整 (转为AMG 509)</td><br />
</tr><br />
</table><br />
</div><br />
</div><br />
<br />
<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：前列腺癌的“免疫导航”</h2><br />
<br />
<p style="margin: 15px 0; text-align: justify;"><br />
[[阿卡帕塔韦]]利用 PSMA 的高度特异性，解决了传统免疫检查点抑制剂（如 PD-1 抗体）在前列腺癌中响应率低的难题：<br />
</p><br />
<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>精准锚定 (PSMA)：</strong> 药物一端结合前列腺特异性膜抗原（PSMA）。该蛋白在超过 80% 的晚期前列腺癌中高表达，就像肿瘤表面的“灯塔”，指引药物富集。</li><br />
<li style="margin-bottom: 12px;"><strong>强制杀伤 (CD3)：</strong> 药物另一端结合 T 细胞的 CD3ε 亚基。无论 T 细胞原本的特异性如何（By-pass MHC restriction），都会被强制激活并释放穿孔素，裂解肿瘤细胞。</li><br />
<li style="margin-bottom: 12px;"><strong>半衰期延长 (HLE)：</strong> 融合的 Fc 结构域通过 FcRn 循环机制，防止药物被肾脏快速滤过，支持<strong>每两周一次</strong>的门诊给药，无需佩戴持续输注泵。</li><br />
</ul><br />
<br />
<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;">临床证据：概念验证与挑战</h2><br />
<br />
<div style="overflow-x: auto; margin: 30px auto; max-width: 95%;"><br />
<table style="width: 100%; border-collapse: collapse; border: 1.2px solid #cbd5e1; font-size: 0.92em; text-align: left;"><br />
<tr style="background-color: #f8fafc; border-bottom: 2px solid #0f172a;"><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">指标</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">Phase 1 数据 (ESMO)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th><br />
</tr><br />
<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">PSA 响应率</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #16a34a;"><strong>34.3%</strong> (PSA下降>50%)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">在平均接受过 4 线治疗的难治性患者中证实了生物学活性。</td><br />
</tr><br />
<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">ORR</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">24.3%</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">部分患者出现明确的肿瘤缩小，证实 BiTE 在冷肿瘤中的潜力。</td><br />
</tr><br />
<tr><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">安全性挑战</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1; color: #b91c1c;">CRS (93%)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">高发的细胞因子释放综合征限制了剂量爬坡，促使后续开发转向毒性更可控的靶点 (STEAP1)。</td><br />
</tr><br />
</table><br />
</div><br />
<br />
<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;">用法用量与管理策略</h2><br />
<br />
<p style="margin: 15px 0; text-align: justify;"><br />
虽然临床开发已调整，但 AMG 160 确立的给药模式成为后续药物的标准模板：<br />
</p><br />
<br />
<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>阶梯给药 (Step-up Dosing)：</strong> 为缓解 [[CRS]]，必需采用起始低剂量、逐步递增至目标剂量的策略。</li><br />
<li style="margin-bottom: 12px;"><strong>预防用药：</strong> 必须预先使用<strong>[[地塞米松]]</strong>以抑制过度的免疫激活。</li><br />
<li style="margin-bottom: 12px;"><strong>给药频率：</strong> 静脉输注，每两周一次 (Q2W)，显著优于第一代 BiTE 的连续泵注。</li><br />
</ul><br />
<br />
<div style="font-size: 0.92em; line-height: 1.6; color: #1e293b; margin-top: 50px; border-top: 2.2px solid #0f172a; padding: 15px 25px; background-color: #f8fafc; border-radius: 0 0 10px 10px;"><br />
<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献 [Academic Review]</span><br />
<br />
<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[1] <strong>Tran B, et al. (2020).</strong> <em>Results from a phase I study of AMG 160, a half-life extended (HLE) PSMA-targeted bispecific T-cell engager (BiTE) therapy in metastatic castration-resistant prostate cancer (mCRPC).</em> <strong>[[Annals of Oncology]]</strong> (ESMO). <br><br />
<span style="color: #475569;">[核心数据]：首次披露 AMG 160 的人体数据，确立了 PSMA BiTE 的临床概念验证 (PoC)。</span><br />
</p><br />
<br />
<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[2] <strong>De Bono JS, et al. (2023).</strong> <em>Emerging targets and therapeutics in metastatic castration-resistant prostate cancer.</em> <strong>[[Nature Reviews Clinical Oncology]]</strong>. <br><br />
<span style="color: #475569;">[综述点评]：分析了 AMG 160 的局限性（CRS毒性）及向 Xaluritamig (AMG 509) 等新一代药物的迭代趋势。</span><br />
</p><br />
</div><br />
<br />
<div style="margin: 40px 0; border: 1px solid #e2e8f0; border-radius: 8px; overflow: hidden; font-family: 'Helvetica Neue', Arial, sans-serif; font-size: 0.9em;"><br />
<div style="background-color: #eff6ff; color: #1e40af; padding: 8px 15px; font-weight: bold; text-align: center; border-bottom: 1px solid #dbeafe;"><br />
阿卡帕塔韦 (AMG 160) · 知识图谱<br />
</div><br />
<table style="width: 100%; border-collapse: collapse; background-color: #ffffff;"><br />
<tr style="border-bottom: 1px solid #f1f5f9;"><br />
<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联技术</td><br />
<td style="padding: 10px 15px; color: #334155;">[[HLE-BiTE]] • [[T细胞重定向]] • [[免疫突触]]</td><br />
</tr><br />
<tr style="border-bottom: 1px solid #f1f5f9;"><br />
<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">迭代药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Xaluritamig]] (AMG 509) • [[Lutetium-177-PSMA-617]] (核素)</td><br />
</tr><br />
<tr style="border-bottom: 1px solid #f1f5f9;"><br />
<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">治疗靶点</td><br />
<td style="padding: 10px 15px; color: #334155;">[[PSMA]] (FOLH1) • [[STEAP1]] (竞品靶点)</td><br />
</tr><br />
<tr><br />
<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">副作用</td><br />
<td style="padding: 10px 15px; color: #334155;">[[CRS]] (细胞因子风暴) • [[味觉障碍]] • [[皮肤毒性]]</td><br />
</tr><br />
</table><br />
</div><br />
<br />
</div></div>
103.220.218.7