m5k1umn 发表于 2024-5-21 14:17:11

《自然-医学》：“量身定制”癌症疫苗治疗肝癌，缓解率近乎翻倍！


    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;">▎药明康德内容团队编辑</span></strong></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">按照</span>国际癌症<span style="color: black;">科研</span><span style="color: black;">公司</span>（IARC）2024年<span style="color: black;">颁布</span>数据，肝癌是<span style="color: black;">全世界</span>第五大高发癌症，死亡人数在所有癌症中位列第三。肝细胞癌（HCC）是最<span style="color: black;">平常</span>的原发性肝癌（约占70%）。<strong style="color: blue;"><span style="color: black;">日前</span>晚期HCC的5年<span style="color: black;">存活</span>率仍不足10%，</strong>治疗<span style="color: black;">选取</span>有限。肝癌对免疫疗法的<span style="color: black;">敏锐</span>性较低，PD-1<span style="color: black;">检测</span>点<span style="color: black;">控制</span>剂单药治疗的缓解率<span style="color: black;">亦</span>仅20%<span style="color: black;">上下</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">个体化治疗性癌症疫苗有<span style="color: black;">潜能</span><span style="color: black;">经过</span>诱导肿瘤特异性免疫来<span style="color: black;">加强</span>肿瘤<span style="color: black;">针对</span>PD-1<span style="color: black;">控制</span>剂的应答。<strong style="color: blue;"><span style="color: black;"><span style="color: black;">近期</span>，《自然-医学》<span style="color: black;">发布</span>一项1/2期临床<span style="color: black;">实验</span>结果，<span style="color: black;">显示</span>个体化治疗性癌症疫苗GNOS-PV02联合PD-1<span style="color: black;">控制</span>剂用于晚期HCC二线治疗安全性良好，缓解率接近单药治疗历史的两倍（30.6% vs 16.9%），且总<span style="color: black;">存活</span>期<span style="color: black;">亦</span>优于既往单药治疗的数据。</span></strong></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://q6.itc.cn/q_70/images03/20240417/b0edd41995a144aeabd88225b7e721d6.png" style="width: 50%; margin-bottom: 20px;"></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;">截图<span style="color: black;">源自</span>：</span></span><span style="color: black;"><span style="color: black;">Nature Medicine</span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;">这款疫苗GNOS-PV02以DNA质粒为载体，能够编码多达40种新抗原。</strong>新抗原指肿瘤基因突变<span style="color: black;">引起</span>肿瘤表达的<span style="color: black;">反常</span>蛋白，而正常宿主细胞中并不会有这些蛋白。<span style="color: black;">经过</span>对<span style="color: black;">病人</span>肿瘤进行测序，<strong style="color: blue;"><span style="color: black;">能够</span><span style="color: black;">发掘</span><span style="color: black;">每一个</span><span style="color: black;">病人</span>独特的肿瘤突变产生的新抗原，</strong><span style="color: black;">而后</span>将表达这些新抗原的DNA序列导入到DNA质粒中。由此，<strong style="color: blue;">疫苗注射到<span style="color: black;">身体</span>后，将激发免疫系统生成肿瘤浸润淋巴细胞（TIL）以识别新抗原并杀死肿瘤细胞。</strong></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">初期</span><span style="color: black;">科研</span><span style="color: black;">表示</span>，<span style="color: black;">病人</span>如对肿瘤新抗原<span style="color: black;">拥有</span>免疫应答，<span style="color: black;">一般</span>对<span style="color: black;">检测</span>点<span style="color: black;">控制</span>剂<span style="color: black;">亦</span><span style="color: black;">拥有</span>更<span style="color: black;">剧烈</span>的应答。<span style="color: black;">因此呢</span>，这项<span style="color: black;">实验</span>中，<span style="color: black;">科研</span>团队<span style="color: black;">选取</span>的治疗策略是，GNOS-PV02、DNA质粒编码的细胞因子IL-12（<span style="color: black;">做为</span>佐剂，强化机体对新抗原的应答）、PD-1<span style="color: black;">控制</span>剂帕博利珠单抗联用。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">实验</span>在36名既往接受过TKI类<span style="color: black;">药品</span>治疗的晚期HCC中开展，至<span style="color: black;">这次</span>数据统计截止日期（2023年8月18日），<span style="color: black;">病人</span>接种疫苗的中位次数为5次（范围1-18），中位治疗<span style="color: black;">连续</span>时间为6.1个月。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;">重点</span>终点为安全性和免疫原性。</strong>最<span style="color: black;">平常</span>的治疗<span style="color: black;">关联</span>不良事件是注射部位反应，<span style="color: black;">出现</span>率为41.6%（15例/36例），未观察到剂量限制性毒性或≥3级<span style="color: black;">治疗<span style="color: black;">关联</span>不良</span>事件。未观察到在PD-1<span style="color: black;">控制</span>剂<span style="color: black;">基本</span>上加用疫苗会降低安全耐受性。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">次要终点为治疗效果和可行性。<strong style="color: blue;">疗效数据支持疫苗联合治疗<span style="color: black;">拥有</span>良好的临床活性：</strong></span></p>

    <span style="color: black;">分别有3例完全缓解和8例部分缓解，<strong style="color: blue;">客观缓解率为30.6%</strong>（11例/36例），相较于帕博利珠单抗单药治疗缓解率的历史对照值（16.9%，参考自KEYNOTE-240），<span style="color: black;">拥有</span>统计学<span style="color: black;">明显</span>性。<span style="color: black;">另外</span>，<strong style="color: blue;"><span style="color: black;">疾患</span><span style="color: black;">掌控</span>率为55.6%</strong>（20例/36例）。</span>
    <span style="color: black;"><span style="color: black;">生效</span>时间方面，治疗至缓解的中位时间为9.3周，中位缓解<span style="color: black;">连续</span>时间尚未达到、仍在<span style="color: black;">累积</span>中。</span>
    <span style="color: black;">中位<span style="color: black;">没</span><span style="color: black;">发展</span><span style="color: black;">存活</span>期为4.2个月，<strong style="color: blue;">中位总<span style="color: black;">存活</span>期为19.9个月。</strong><span style="color: black;">疾患</span>缓解<span style="color: black;">状况</span>与<span style="color: black;">存活</span>期密切<span style="color: black;">关联</span>。值得一提的是，<strong style="color: blue;"><span style="color: black;">日前</span>的中位总<span style="color: black;">存活</span>期数据<span style="color: black;">亦</span>优于既往PD-1<span style="color: black;">控制</span>剂单药二线治疗肝癌的数据</strong>（12.9~15.1个月）。</span>

    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;">进一步免疫学分析证实了这款疫苗的治疗<span style="color: black;">功效</span>机制。</strong></span></p>

    <span style="color: black;">疫苗接种能够诱导新抗原特异性应答：22例可<span style="color: black;">评定</span><span style="color: black;">病人</span>中有19例（86.4%）证实<span style="color: black;">拥有</span>新抗原特异性T细胞应答。</span>
    <span style="color: black;">疫苗接种促进T细胞克隆扩增和浸润：在14例可<span style="color: black;">评定</span>的<span style="color: black;">病人</span>中，100%在外周血和肿瘤组织中有<span style="color: black;">明显</span>的T细胞克隆扩增。单细胞测序分析<span style="color: black;">表示</span>，这些T细胞克隆绝大<span style="color: black;">都数</span>是CD8 T效应记忆细胞，这是诱导抗肿瘤细胞毒性的<span style="color: black;">重要</span>。</span>
    <span style="color: black;">两名<span style="color: black;">表率</span>性<span style="color: black;">病人</span>的数据进一步证实了肿瘤浸润T细胞对新抗原<span style="color: black;">拥有</span>特异性活性。</span>

    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">总体而言，<strong style="color: blue;"><span style="color: black;">这项<span style="color: black;">实验</span>结果支持个体化治疗性癌症疫苗能够诱导抗肿瘤T细胞生成，且联合帕博利珠单抗治疗<span style="color: black;">拥有</span>临床活性。</span></strong></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;">点击文末“阅读原文/Read more”，<span style="color: black;">就可</span><span style="color: black;">拜访</span></span></span></span><span style="color: black;"><span style="color: black;">Nature Medicine</span></span><span style="color: black;"><span style="color: black;"><span style="color: black;">官网阅读完整论文。</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;">樊嘉院士等人<span style="color: black;">发布</span>重磅综述！晚期肝癌治疗有望迎来三类“新武器”！</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">在多种癌症中产生应答，癌症疫苗复兴时代来临！</span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;">没</span>复发<span style="color: black;">存活</span>16个月！《自然-医学》：通用癌症疫苗，突破“难以成药”</span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">82%晚期癌症<span style="color: black;">病人</span>客观缓解！癌症疫苗2期<span style="color: black;">实验</span>数据亮眼</span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;"><span style="color: black;">欢迎投稿：</span></span></strong><span style="color: black;"><span style="color: black;">学术成果、前沿<span style="color: black;">发展</span>、临床干货等主题均可，</span></span><span style="color: black;"><span style="color: black;">点此<span style="color: black;">认识</span>投稿详情</span></span><span style="color: black;">。</span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;">题图<span style="color: black;">源自</span>：123RF</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;">参考资料（可上下滑动查看）</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;"> Yarchoan, M., Gane, E.J., Marron, T.U. et al. (2024). Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial. Nat Med, DOI: https://doi.org/10.1038/s41591-024-02894-y</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;"> Global cancer burden growing, amidst mounting need for services. Retrieved April 10, 2024 from https://www.who.int/news/item/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;"> Cancer Facts &amp; Figures 2024 Retrieved April 10, 2024 from https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2024-cancer-facts-figures.html</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;"> Geneos Therapeutics. Retrieved April 10, 2024 from https://www.geneostx.com/</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><span style="color: black;"><span style="color: black;"> Geneos Therapeutics Announces Positive Phase 1/2 Data for GT-30 Trial of Personalized Therapeutic Cancer Vaccine. Retrieved April 10, 2024 from https://www.geneostx.com/geneos-therapeutics-announces-positive-phase-1-2-data-for-gt-30-trial-of-personalized-therapeutic-cancer-vaccine/</span></span></span></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">源自</span>：<span style="color: black;"><span style="color: black;">医学新视点</span></span></span><a style="color: black;"><span style="color: black;">返回首页，查看<span style="color: black;">更加多</span></span></a></p>

    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">外链论坛：http://www.fok120.com/</p>




4lqedz 发表于 2024-10-6 08:29:37

太棒了、厉害、为你打call、点赞、非常精彩等。

1fy07h 发表于 2024-10-20 23:10:13

感谢楼主的分享！我学到了很多。

b1gc8v 发表于 2024-10-25 09:54:57

感谢你的精彩评论，为我的思绪打开了新的窗口。

qzmjef 发表于 2024-10-28 11:55:37

软文发布论坛开幕式圆满成功。 http://www.fok120.com
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查看完整版本: 《自然-医学》：“量身定制”癌症疫苗治疗肝癌，缓解率近乎翻倍！