LAG-3靶向疗法“牵手”PD-1掌控剂治疗癌症,效果积极
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">4月24日,Immutep<span style="color: black;">机构</span><span style="color: black;">颁布</span>了2b期<span style="color: black;">实验</span>TACTI-003(KEYNOTE-PNC-34)队列B 的初步顶线结果。该<span style="color: black;">实验</span>旨在<span style="color: black;">评定</span>eftilagmod alpha(efti)联合默沙东(MSD)抗PD-1抗体Keytruda(pembrolizumab)一线治疗PD-L1阴性的复发/转移性头颈鳞状细胞癌<span style="color: black;">病人</span>的疗效。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">Immutep是一家总部<span style="color: black;">位置于</span>澳大利亚的临床<span style="color: black;">周期</span>生物技术<span style="color: black;">机构</span>,正在<span style="color: black;">研发</span>针对癌症和<span style="color: black;">自己</span>免疫性<span style="color: black;">疾患</span>的新型LAG-3免疫疗法。Efti是该<span style="color: black;">机构</span><span style="color: black;">研发</span>的一种可溶性LAG-3蛋白和MHC II类激动剂,此前已<span style="color: black;">得到</span>美国FDA授予一线治疗头颈鳞状细胞癌<span style="color: black;">病人</span>的快速通道资格。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q7.itc.cn/images01/20240426/4d9683212523471cb0bad508e65bbb5d.png" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">LAG-3蛋白能够调控T淋巴细胞和抗原呈递细胞(APCs)的信号通路,在适应性免疫反应中起到<span style="color: black;">要紧</span><span style="color: black;">功效</span>。可溶性LAG-3<span style="color: black;">经过</span>与APC表面的<span style="color: black;">重点</span>组织相容性复合体II(MHC II)相结合,能够激活APCs,这会<span style="color: black;">引起</span>细胞毒性CD8阳性T细胞数量的<span style="color: black;">增多</span>和激活。<span style="color: black;">经过</span>这一机制,可溶性LAG-3蛋白能够<span style="color: black;">加强</span>对癌症抗原的免疫反应。已有<span style="color: black;">科研</span>显示,将抗LAG-3抗体与抗PD-1抗体联用,可能达到协同激活T细胞的效果。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">Efti为一种可溶性LAG-3融合蛋白和MHC II类激动剂,可<span style="color: black;">经过</span>刺激先天免疫和适应性免疫来治疗癌症。它利用LAG-3<span style="color: black;">能够</span>与树突状细胞、单核细胞、巨噬细胞等抗原呈递细胞结合的特性,抵抗肿瘤细胞的扩增,以及将抗原呈递给适应性免疫系统,激发CD4阳性和CD8阳性T细胞的增殖。<span style="color: black;">日前</span>,<span style="color: black;">科研</span>人员正在针对多种实体瘤的<span style="color: black;">实验</span>中对efti进行<span style="color: black;">评定</span>,<span style="color: black;">包含</span>非小细胞肺癌、头颈鳞状细胞癌和转移性乳腺癌。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">TACTI-003<span style="color: black;">实验</span>是一项正在进行的2b期<span style="color: black;">科研</span>,旨在<span style="color: black;">评定</span>efti与pembrolizumab<span style="color: black;">做为</span>复发性或转移性头颈鳞状细胞癌(HNSCC)一线治疗的效果。该<span style="color: black;">科研</span>的随机队列A部分正在<span style="color: black;">评定</span>efti与pembrolizumab联合治疗与pembrolizumab单药疗法在PD-L1阳性肿瘤<span style="color: black;">病人</span>中的疗效,而队列B正在<span style="color: black;">评定</span>efti与pembrolizumab联合治疗PD-L1阴性肿瘤<span style="color: black;">病人</span>的疗效。该<span style="color: black;">科研</span>的<span style="color: black;">重点</span>终点是<span style="color: black;">按照</span>RECIST 1.1可<span style="color: black;">评定</span><span style="color: black;">病人</span>的总体缓解率。次要终点<span style="color: black;">包含</span>总<span style="color: black;">存活</span>期、<span style="color: black;">按照</span>iRECIST的总缓解率、<span style="color: black;">没</span><span style="color: black;">发展</span><span style="color: black;">存活</span>期和缓解<span style="color: black;">连续</span>时间。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">这次</span><span style="color: black;">颁布</span>的队列B的初步顶线结果<span style="color: black;">表示</span>,在26名不表达PD-L1的肿瘤<span style="color: black;">病人</span>中,接受 Immutep<span style="color: black;">机构</span>的可溶性LAG-3蛋白efti和默沙东的抗PD-1抗体组合的<span style="color: black;">病人</span>,达到了26.9%的客观缓解率(ORR)和57.7%的<span style="color: black;">疾患</span><span style="color: black;">掌控</span>率(DCR)。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">TACTI-003<span style="color: black;">实验</span>的<span style="color: black;">科研</span>者、英国伦敦大学癌症<span style="color: black;">科研</span>所和伦敦大学学院医院NHS基金会的Martin Forster博士<span style="color: black;">暗示</span>,<span style="color: black;">针对</span>PD-L1阴性的头颈鳞状细胞癌的<span style="color: black;">病人</span>,这些初步的积极结果是令人鼓舞的。头颈鳞状细胞癌是一种异质性<span style="color: black;">疾患</span>,<span style="color: black;">没</span>论PD-L1表达<span style="color: black;">怎样</span>,<span style="color: black;">她们</span>都有着高度未满足的医疗需求,<span style="color: black;">针对</span>不表达PD-L1的肿瘤<span style="color: black;">病人</span>和<span style="color: black;">没</span>法接受化疗的<span style="color: black;">病人</span>尤其如此。Efti与默沙东的抗PD-1抗体Keytruda<span style="color: black;">协同</span><span style="color: black;">运用</span>,<span style="color: black;">表示</span>出了能够在不<span style="color: black;">运用</span>化疗的<span style="color: black;">状况</span>下改善<span style="color: black;">病人</span>的临床反应并扩大对Keytruda有反应的<span style="color: black;">病人</span>群体的<span style="color: black;">潜能</span>。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">按照</span>Immutep<span style="color: black;">机构</span><span style="color: black;">资讯</span>稿,TACTI-003的数据收集、清理和分析仍在继续,该<span style="color: black;">机构</span>预计将在2024年上半年报告队列A和B的<span style="color: black;">重点</span>终点ORR的数据。</p>
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