论坛 › 山东 › 抢先看！2019ASCO癌症疫苗最新发展

tw4ld6 发表于 2024-6-24 08:17:42

抢先看！2019ASCO癌症疫苗最新发展

    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_gif/vl8De1ZSQccPibxlqVfMias1Y1ribDUOGrXCRaoBlIHoxxSLVSz8Vdrd7JYPeBy4fZRu90gut9Xp58SRNNBHZ0Hew/640?wx_fmt=gif&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1" 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;">源自</span>：美柏医健</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">正文共：8121字</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">预计阅读时间：&nbsp;21分钟</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">在癌症治疗<span style="color: black;">行业</span>，免疫治疗携带多项成果<span style="color: black;">已然</span>崭露头角，而癌症疫苗<span style="color: black;">做为</span>其中的<span style="color: black;">科研</span>热点<span style="color: black;">亦</span>初露端倪。癌症疫苗不仅有着普通疫苗的预防<span style="color: black;">功效</span>，<span style="color: black;">例如</span>宫颈癌疫苗，<span style="color: black;">亦</span>能以治疗性疫苗发挥着激活人体免疫系统的<span style="color: black;">功效</span>，杀伤肿瘤细胞。</p>

    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">癌症疫苗种类繁多，<span style="color: black;">包含</span>细胞疫苗、核酸疫苗、蛋白多肽疫苗和基因工程疫苗等。<span style="color: black;">没</span>论何种疫苗，都是将肿瘤抗原呈递给免疫细胞，激活免疫反应，从而达到抗癌效果。今年美国临床肿瘤学会（ASCO）上<span style="color: black;">亦</span>重点收录了<span style="color: black;">有些</span>癌症疫苗<span style="color: black;">发展</span>，<span style="color: black;">咱们</span>将与<span style="color: black;">大众</span>分享！</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">&nbsp;RNA疫苗&nbsp;</span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/5PZN1kpaxrFH266suqUcl6nicb11wrhfiaZgBfszA8AjAfmr3W8KM8TztEgwB1Q0ZxCNlWibMnb8rEmkssWBTPsBQ/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" 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;">核酸疫苗是将编码某种抗原蛋白的外源基因(DNA 或RNA ) 直接导入动物体细胞内，并<span style="color: black;">经过</span>宿主细胞的表达系统合成抗原蛋白，诱导宿主产生对该抗原蛋白的免疫应答，以达到预防和治疗<span style="color: black;">疾患</span>的目的。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">肿瘤RNA疫苗，顾名思义，则是将肿瘤抗原的RNA导入<span style="color: black;">身体</span>，产生免疫应答而达到抗癌效果。<span style="color: black;">通常</span><span style="color: black;">来讲</span>，RNA疫苗<span style="color: black;">运用</span>信使RNA（mRNA），这是翻译成蛋白质的模板。今年ASCO上共有三项mRNA疫苗的介绍，<span style="color: black;">咱们</span>将逐项讲解。</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;">第1</span><span style="color: black;">科研</span>关于癌症疫苗mRNA-4157单药在可切除实体瘤以及联合PD-1抗体K药在不可切除实体瘤中的应用。这是一项剂量爬坡一期临床<span style="color: black;">实验</span>，<span style="color: black;">重点</span>终点检测<span style="color: black;">药品</span>的安全性、有效性和免疫原性。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">mRNA-4157是一种编码多种新抗原的脂质类个性化疫苗，用以诱导新抗原特异T细胞和<span style="color: black;">关联</span>抗癌反应。<span style="color: black;">病人</span>接受不同剂量多达9个疗程的疫苗注射。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">总共33名<span style="color: black;">病人</span>接受了mRNA-4157治疗，其中13人为单药，20名联合K药。<span style="color: black;">无</span>剂量限制毒性（DLT）被<span style="color: black;">报道</span>，治疗<span style="color: black;">关联</span>副<span style="color: black;">功效</span><span style="color: black;">亦</span>较低且是可逆的，<span style="color: black;">亦</span><span style="color: black;">无</span>观察到等级超过3的<span style="color: black;">药品</span><span style="color: black;">关联</span>副<span style="color: black;">功效</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">在13名辅助单药治疗的<span style="color: black;">病人</span>中，12名依旧保持<span style="color: black;">没</span><span style="color: black;">疾患</span>状态，中位随访期为8个月。联合用药的20名<span style="color: black;">病人</span>中，其中12人对前期的免疫检测点<span style="color: black;">控制</span>剂耐药。<span style="color: black;">最后</span>16名<span style="color: black;">病人</span>肿瘤分期<span style="color: black;">出现</span>改变：5个<span style="color: black;">药品</span>联合疗程内产生1个CR，2 PR，5 SD，而5 PD，2 iuPD和1个<span style="color: black;">没</span>法<span style="color: black;">评定</span><span style="color: black;">病人</span>仍在<span style="color: black;">科研</span>中【1】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">这项<span style="color: black;">科研</span>提示<span style="color: black;">咱们</span>mRNA-4157在实体瘤中的安全性和耐受性，以及联合K药产生的有效性，<span style="color: black;">能够</span>推进到二期临床<span style="color: black;">实验</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">第二项<span style="color: black;">科研</span>是名为ECI-006癌症疫苗在可切除黑色素瘤中的一期临床<span style="color: black;">科研</span>。ECI-006是一混合疫苗，<span style="color: black;">包含</span><span style="color: black;">各样</span>DC激活分子和黑色素瘤特异肿瘤<span style="color: black;">关联</span>抗原（TAA）的mRNA。<span style="color: black;">科研</span>目的为了验证ECI-006<span style="color: black;">做为</span>辅助治疗的安全性和免疫原性。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">20名2c-4期手术黑色素瘤<span style="color: black;">病人</span>接受5次ECI-006注射，分别在第1天、第2、4、6和14周。<span style="color: black;">最后</span>19名<span style="color: black;">病人</span>完成治疗，1名低剂量组<span style="color: black;">病人</span><span style="color: black;">因为</span><span style="color: black;">疾患</span>复发而终止治疗。ECI-006耐受性良好，未<span style="color: black;">发掘</span>超过3级严重副<span style="color: black;">功效</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">所有治疗<span style="color: black;">关联</span>副<span style="color: black;">功效</span>中，肌痛 (15%)和疲劳 (25%)<span style="color: black;">报道</span>最多。<span style="color: black;">按照</span>既定标准，低剂量和高剂量组分别有4/10和3/9<span style="color: black;">病人</span>产生疫苗诱导免疫响应。ECI-006的耐受性和免疫原性<span style="color: black;">亦</span>为后续与PD-1抗体联合<span style="color: black;">供给</span>了临床依据【2】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">最后一项<span style="color: black;">科研</span><span style="color: black;">研发</span>了针对肿瘤细胞的新抗原，并<span style="color: black;">经过</span>抗原表位设计mRNA疫苗靶向这种新抗原，从而达到抗肿瘤的目的。新抗原对肿瘤个性化治疗至关<span style="color: black;">要紧</span>，<span style="color: black;">科研</span><span style="color: black;">亦</span>证明新抗原特异T细胞存在于大<span style="color: black;">都数</span>肿瘤中，是个性化疫苗的<span style="color: black;">要紧</span>靶点。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">该<span style="color: black;">科研</span><span style="color: black;">经过</span>肿瘤浸润淋巴细胞鉴定出肿瘤特异突变，并<span style="color: black;">这里</span><span style="color: black;">基本</span>上<span style="color: black;">研发</span>鉴定出T细胞抗原表位。这是首次在转移上皮细胞癌中鉴定新抗原，预测新抗原表位和突变，并<span style="color: black;">最后</span><span style="color: black;">研发</span>出名为mRNA-4650的癌症疫苗。</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;">日前</span>这款疫苗正在<span style="color: black;">最少</span>有一个可切除位点的转移性黑色素瘤、胃癌和泌尿生殖癌<span style="color: black;">病人</span>中进行一期/二期临床<span style="color: black;">实验</span>。<span style="color: black;">病人</span>每两周注射一次疫苗，共四个疗程。<span style="color: black;">重点</span>终点是安全性、耐受性、T细胞响应以及ORR。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">结果<span style="color: black;">显示</span>：mRNA-4650所有剂量均安全，<span style="color: black;">无</span><span style="color: black;">发掘</span>DLT和<span style="color: black;">药品</span><span style="color: black;">关联</span>严重副<span style="color: black;">功效</span>。<span style="color: black;">科研</span>观察到响应新抗原表位的特异CD8和CD4 T细胞，但未观察到肿瘤消退。<span style="color: black;">不外</span>，这为与免疫检测点<span style="color: black;">控制</span>剂和过继T细胞治疗<span style="color: black;">供给</span>了可能性【3】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">&nbsp;多肽疫苗&nbsp;</span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/5PZN1kpaxrFH266suqUcl6nicb11wrhfiaIqS9xiafILAvea1YhDQxgBy2SzjD4B5pMmRdt0Y4Mx7LZBbqxY2OalQ/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" 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;">多肽疫苗是<span style="color: black;">根据</span>病原体抗原基因中已知或预测的某段抗原表位的氨基酸序列，<span style="color: black;">经过</span>化学合成技术制备的疫苗。<span style="color: black;">倘若</span>能找到肿瘤细胞中特异的抗原，并以此氨基酸序列<span style="color: black;">研发</span>癌症疫苗，能够激活<span style="color: black;">关联</span>免疫细胞杀伤<span style="color: black;">详细</span>相同抗原的肿瘤细胞。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">今年ASCO有两项关于多肽癌症疫苗的<span style="color: black;">科研</span>：<span style="color: black;">第1</span>项是多种多肽疫苗混合在侵袭性肿瘤中的应用；第二项是基于新抗原的多肽疫苗的临床疗效。</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;">第1</span>项<span style="color: black;">科研</span>中，侵袭性癌症<span style="color: black;">病人</span>的肿瘤和淋巴结微环境之间的<span style="color: black;">科研</span>不多，<span style="color: black;">亦</span><span style="color: black;">无</span>行之有效的途径来进行调控。<span style="color: black;">不外</span>，多种多肽疫苗治疗或许能<span style="color: black;">处理</span>这种问题，<span style="color: black;">况且</span>在临床安全性上<span style="color: black;">亦</span>能得到<span style="color: black;">保证</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">该<span style="color: black;">科研</span>总招募了11名<span style="color: black;">病人</span>，并<span style="color: black;">经过</span><span style="color: black;">各样</span><span style="color: black;">办法</span>确定了众多的靶点。<span style="color: black;">病人</span>先每隔<span style="color: black;">1星期</span>在淋巴结处皮下注射疫苗，共8次。<span style="color: black;">而后</span>在<span style="color: black;">经过</span>CT或PET在肿瘤活性部位皮下注射疫苗，共10次。</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;">科研</span>结果<span style="color: black;">表示</span>：<span style="color: black;">没</span>论<span style="color: black;">疾患</span><span style="color: black;">发展</span><span style="color: black;">状况</span><span style="color: black;">怎样</span>，100%的<span style="color: black;">病人</span>对治疗产生响应，其中80%达到CR，20%假性<span style="color: black;">发展</span><span style="color: black;">病人</span>后来<span style="color: black;">亦</span>发展为CR。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">100%<span style="color: black;">病人</span>靶向Bcl-2 (p = 0.001), VCP (p = 0.0001), Ape-1 (p = 0.005)和RCAS1 (P = 0.0001)的Granzyme B水平得到<span style="color: black;">加强</span>，治疗后扫描数据<span style="color: black;">亦</span>得到<span style="color: black;">类似</span>结果。</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;">病人</span>在肿瘤位点(p = 0.002)比非肿瘤位点(p = 0.01)<span style="color: black;">表示</span>出<span style="color: black;">更加多</span>的CD8 T细胞浸润。<span style="color: black;">病人</span><span style="color: black;">身体</span>肺(p = 0.004)和肝(p = 0.001)转移消失的数目与IL-12<span style="color: black;">提升</span>呈<span style="color: black;">明显</span>关系。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">这项<span style="color: black;">科研</span>说明在多种实体瘤的淋巴结和肿瘤位点注射多种多肽疫苗不仅安全<span style="color: black;">靠谱</span>，<span style="color: black;">亦</span>能<span style="color: black;">加强</span>晚期病人的临床受益【4】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">第二项<span style="color: black;">科研</span>中，新抗原疫苗能够激活T细胞<span style="color: black;">从而</span>杀伤肿瘤细胞。然而，大<span style="color: black;">都数</span>多肽疫苗要么<span style="color: black;">选取</span>HLA结合表位，要么<span style="color: black;">选取</span>HLA呈递表位，都<span style="color: black;">不可</span>诱导个性化T细胞响应。该<span style="color: black;">科研</span>认为结合到多种自体HLA等位基因的个性化表位<span style="color: black;">能够</span>诱导T细胞响应。</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;">科研</span>人员在两项临床<span style="color: black;">实验</span>中给<span style="color: black;">病人</span>注射了合成长链多肽（SLP）疫苗，分别鉴定出单HLA和3 HLA等位基因的抗原表位，并<span style="color: black;">经过</span>CD8和CD4 T细胞响应得以验证。<span style="color: black;">最后</span>，<span style="color: black;">她们</span><span style="color: black;">研发</span>出一种个性化疫苗，能结合从12种肿瘤抗原<span style="color: black;">源自</span>的14个HLA等位基因。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">结果<span style="color: black;">表示</span>：单HLA结合表位和HPV特异T细胞响应<span style="color: black;">无</span><span style="color: black;">关联</span>性。相反，一类HLA个性化抗原表位与CD8 T细胞响应一致性为90% (p &lt; 0.001)，二类HLA个性化抗原表位与CD4 T细胞响应一致性为69% (p = 0.005)。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">个性化抗原表位的数值<span style="color: black;">能够</span>预测SLP疫苗临床<span style="color: black;">实验</span>的T细胞响应率。经预测，91%和100%的多肽疫苗能分别诱导CD8和CD4 T细胞响应【5】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">&nbsp;DC疫苗&nbsp;</span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/5PZN1kpaxrFH266suqUcl6nicb11wrhfiaLxYlgiaXum6Un8ZoSadA2j2BfUp6rvo8iaXBnnk1ickOmmybMCIxEg0yg/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" 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;">DC细胞俗<span style="color: black;">叫作</span>树突状细胞，因成熟时伸出许多树突样或伪足样突起而得名。DC是人<span style="color: black;">身体</span>抗原递呈能力最强的细胞。这些细胞能有效识别抗原，并把抗原呈递给免疫细胞，激活<span style="color: black;">得到</span>性免疫系统，产生正常的免疫反应。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">DC疫苗<span style="color: black;">经过</span>采用病人自体的单核细胞在体外培养诱导生成DC，<span style="color: black;">而后</span>负载相应的肿瘤抗原，制成负载肿瘤抗原的DC，再将这些DC细胞注入<span style="color: black;">身体</span>后刺激<span style="color: black;">身体</span>的肿瘤杀伤性淋巴细胞增殖，发挥<span style="color: black;">长时间</span>肿瘤<span style="color: black;">监测</span><span style="color: black;">功效</span>和肿瘤杀伤<span style="color: black;">功效</span>，达到消灭肿瘤的目的。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">今年ASCO有两项关于DC疫苗的<span style="color: black;">报告</span>。<span style="color: black;">第1</span>项是关于自体DC疫苗在转移性黑色素瘤中的<span style="color: black;">科研</span>；第二项是靶向HER2的DC疫苗在转移性癌症中的<span style="color: black;">科研</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">在<span style="color: black;">第1</span>项<span style="color: black;">科研</span>中，<span style="color: black;">初期</span><span style="color: black;">科研</span><span style="color: black;">发掘</span>癌症<span style="color: black;">病人</span><span style="color: black;">存活</span>深受肿瘤分期和负荷的影响。而这项<span style="color: black;">科研</span>的目的<span style="color: black;">便是</span>为了揭示黑色素瘤<span style="color: black;">病人</span><span style="color: black;">存活</span>期与接受特异疫苗之间的关系。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">所有<span style="color: black;">病人</span><span style="color: black;">拥有</span>可切除的肿瘤部分，并将其培养成肿瘤细胞系。细胞系经射线照射后，与DC<span style="color: black;">一块</span>培养产生DC疫苗。疫苗先每周注射一次，连续三周；<span style="color: black;">而后</span>每月注射一次，连续五个月。该<span style="color: black;">科研</span>收集了两项二期临床数据：一项单臂(NCT00948480)，一项随机(NCT00436930)。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">这项数据<span style="color: black;">包含</span>45名男性和27名女性，平均年龄52岁（17-83）。肿瘤<span style="color: black;">源自</span>为37例淋巴结、20例内脏和15例软组织。所有存活<span style="color: black;">病人</span>经历了5年随访，<span style="color: black;">仅有</span>轻微细胞毒性。所有72位<span style="color: black;">病人</span>的中位OS为49.4个月，5年OS为46%。</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;">存活</span>期与<span style="color: black;">初始</span>三次注射的DC和照射肿瘤细胞的数量<span style="color: black;">无</span><span style="color: black;">关联</span>性。复发3期<span style="color: black;">病人</span>(n=18) 5年OS为72%，不可<span style="color: black;">测绘</span>4期<span style="color: black;">病人</span>(n=30) 5年OS为53%。可<span style="color: black;">测绘</span>4期<span style="color: black;">病人</span>(n=18)经历了平均4次前治疗，<span style="color: black;">她们</span>中位OS为18.5个月，2年OS为46%【6】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">在第二项<span style="color: black;">科研</span>中，<span style="color: black;">科研</span>者<span style="color: black;">研发</span>出靶向HER2的自体DC疫苗，<span style="color: black;">经过</span>腺病毒转导。在动物实验中，这种疫苗治愈了所有肿瘤移植小鼠。这项<span style="color: black;">科研</span>将这些<span style="color: black;">发掘</span>转化为临床<span style="color: black;">实验</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">这是一项开放的一期临床<span style="color: black;">实验</span>，招募<span style="color: black;">病人</span>标准有两条：一是经过<span style="color: black;">最少</span>一次标准治疗后<span style="color: black;">发展</span>的转移性肿瘤<span style="color: black;">病人</span>；二是HER2免疫组化水平较高的高<span style="color: black;">危害</span>膀胱癌<span style="color: black;">病人</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;">第1</span>部分<span style="color: black;">病人</span>中，最低剂量疫苗（5ⅹ106细胞，N=7，2人未能<span style="color: black;">评定</span>）并<span style="color: black;">没</span>临床受益。在第二和第三剂量水平（107和2ⅹ107细胞，N=7和N=4，分别有0和1人未能<span style="color: black;">评定</span>），观察到1个CR（卵巢癌），1个PR（胃癌）和3个SD（1个卵巢癌和2个结肠癌）。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">两名接受疫苗<span style="color: black;">做为</span>辅助治疗的<span style="color: black;">病人</span>在超过24和36个月<span style="color: black;">无</span>复发。第二部分<span style="color: black;">病人</span>中（N=6，2人未能<span style="color: black;">评定</span>），1男性乳腺癌<span style="color: black;">病人</span><span style="color: black;">表示</span>SD。<span style="color: black;">科研</span><span style="color: black;">发掘</span>两年随访未<span style="color: black;">发掘</span>心脏毒性。下表是响应<span style="color: black;">评定</span>数据【7】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/5PZN1kpaxrFH266suqUcl6nicb11wrhfiaJZv4BTDlaxTQJAImXvBK1iacYicsC3r7qibCJcZfQdKpslKf6OXgHNczg/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">&nbsp;基因工程疫苗&nbsp;</span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/5PZN1kpaxrFH266suqUcl6nicb11wrhfiaM01ibGTmczNxjfuXicnk3ibZHCSNIibWjBiccEBoMmskNHribTEBLpHJSsVA/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" 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;">基因工程疫苗是将病原的<span style="color: black;">守护</span>性抗原编码的基因片段克隆入表达载体，用以转染细胞或真核细胞微生物及原核细胞微生物后得到的产物。<span style="color: black;">或</span>将病原的毒力<span style="color: black;">关联</span>基因删除掉, 使<span style="color: black;">作为</span>不带毒力<span style="color: black;">关联</span>基因的基因缺失疫苗。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">今年ASCO<span style="color: black;">报道</span>了两项基因工程疫苗的<span style="color: black;">科研</span>。<span style="color: black;">第1</span>项关于沙粒病毒淋巴细胞性脉络丛脑膜炎病毒（LCMV）疫苗在HPV16驱动的癌症中的<span style="color: black;">科研</span>；第二项关于沙粒病毒载体平台促进CD8 T细胞免疫<span style="color: black;">关联</span><span style="color: black;">科研</span>。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">在<span style="color: black;">第1</span>项<span style="color: black;">科研</span>中，癌症的有效免疫<span style="color: black;">必须</span>诱导肿瘤特异CD8 T细胞（CTL）响应，这种响应<span style="color: black;">能够</span><span style="color: black;">连续</span>反复激活。Hookipa医药<span style="color: black;">机构</span>基于LCMV工程化了一个病毒载体平台(TheraT)。这项<span style="color: black;">科研</span><span style="color: black;">供给</span>了其中一种先导<span style="color: black;">制品</span>HB-201在HPV16驱动癌症中的临床前数据。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">TheraT-E7E6编码了高度免疫原性但非致癌的HPV16癌蛋白E7和E6。TheraT-E7E6的安全性<span style="color: black;">经过</span>两种方式<span style="color: black;">表现</span>：一是载体系统给药后的快速清除，二是在小鼠<span style="color: black;">身体</span>降低神经毒性。TheraT-E7E6<span style="color: black;">能够</span>皮下注射<span style="color: black;">做为</span>系统治疗，<span style="color: black;">亦</span>能瘤内注射<span style="color: black;">做为</span>局部治疗。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">治疗结果<span style="color: black;">表示</span>疫苗诱导出<span style="color: black;">海量</span>的CD8 T细胞增殖和高频E7和E6特异CTL响应，<span style="color: black;">伴同</span><span style="color: black;">平衡</span>的效应/中心记忆T细胞群体。这些响应在继续注射TheraT-E7E6会进一步<span style="color: black;">提高</span>和激活。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">TheraT-E7E6<span style="color: black;">明显</span>降低了同系小鼠TC-1肿瘤模型的肿瘤负荷，这是一种HPV驱动的模型。即使在高肿瘤负荷(~300mm3)小鼠中，TheraT-E7E6<span style="color: black;">亦</span>能<span style="color: black;">明显</span><span style="color: black;">掌控</span>肿瘤生长和<span style="color: black;">加强</span><span style="color: black;">存活</span>率，<span style="color: black;">拥有</span>高频的E7特异CTL能维持<span style="color: black;">几周</span>之久。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">TheraT治疗后肿瘤根除的动物可维持长效免受肿瘤再攻击。<span style="color: black;">另一</span>，TheraT在免疫检测点抑制剂复发模型中<span style="color: black;">亦</span><span style="color: black;">表示</span>出有效性，并且能够与这些<span style="color: black;">控制</span>剂联合达到协同<span style="color: black;">功效</span>【8】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">在第二项<span style="color: black;">科研</span>中，诱导出对TAA强力CD8 T细胞免疫是肿瘤治疗中<span style="color: black;">重要</span>且充满挑战的<span style="color: black;">目的</span>。这项<span style="color: black;">科研</span><span style="color: black;">经过</span><span style="color: black;">研发</span>基于沙粒病毒递送平台来应对这项挑战。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">此前<span style="color: black;">科研</span><span style="color: black;">表示</span>：基因工程化LCMV载体TheraT虽然能够诱导TAA特异CD8 T细胞免疫，但重新注射这些载体并<span style="color: black;">不可</span><span style="color: black;">提高</span><span style="color: black;">连续</span>响应。<span style="color: black;">因此呢</span>，<span style="color: black;">科研</span>者工程化以及特化了基于不同沙粒病毒的递送平台。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">结果<span style="color: black;">表示</span>：异源TheraT(CAND) – TheraT(LCMV)和TheraT(PIC)-TheraT(LCMV)能<span style="color: black;">经过</span><span style="color: black;">增多</span>免疫显性而<span style="color: black;">连续</span><span style="color: black;">提高</span>TAA特异CD8 T细胞响应。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">相应地，小鼠尾静脉注射疫苗促发50% TAA抗原表位特异CD8 T细胞响应，并治愈了移植肿瘤。相反，TheraT(MOP) – TheraT(LCMV)<span style="color: black;">因为</span>T细胞抗原表位交叉反应而<span style="color: black;">拥有</span>较差免疫原性，<span style="color: black;">不可</span>有效激活T细胞免疫【9】。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">&nbsp;小结&nbsp;</span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">疫苗的诞生使人类摆脱了众多传染性<span style="color: black;">疾患</span>的<span style="color: black;">困惑</span>，而接种疫苗<span style="color: black;">亦</span><span style="color: black;">作为</span><span style="color: black;">每一个</span>人不可或缺的经历。癌症疫苗的概念不仅<span style="color: black;">能够</span>使<span style="color: black;">咱们</span>对<span style="color: black;">疾患</span>防患于未然，<span style="color: black;">亦</span>能激活人体的免疫系统来战胜癌症。但<span style="color: black;">因为</span>癌症本身是一种<span style="color: black;">繁杂</span>的<span style="color: black;">疾患</span>，<span style="color: black;">明显</span>还<span style="color: black;">无</span>一种疫苗能抵抗所有癌症。</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><a style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_png/vl8De1ZSQccE3SZibTkdulUbG91J4HclQmOG8SDcA0s1QI0icfXicicd3pyVYuVm13UIibsiauBIz7k2QJjXicGa5th2w/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"></a></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">ASCO的<span style="color: black;">科研</span>使<span style="color: black;">咱们</span>认识到，不同癌症不同<span style="color: black;">病人</span>存在着不同的抗原，<span style="color: black;">仅有</span>找出这些特异的抗原，针对性地<span style="color: black;">研发</span>出<span style="color: black;">关联</span>疫苗，<span style="color: black;">才可</span>有的放矢的激活<span style="color: black;">病人</span>免疫系统，<span style="color: black;">控制</span>肿瘤细胞的生长。癌症疫苗联合其他疗法有可能更好地发挥效应，使<span style="color: black;">病人</span>更大程度地获益！</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">参考文献：</span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【1】Howard A. Burris, Manish R. Patel, Daniel C. Cho, Jeffrey Melson Clarke, Martin Gutierrez, Tal Z. Zaks, Joshua Frederick, Kristen Hopson, Kinjal Mody, Alverina Binanti-Berube, Celine Robert-Tissot, Bree Goldstein, Ben Breton, Jing Sun, Shan Zhong, Scott K. Pruitt, Karen Keating, Robert S. Meehan, Justin F. Gainor. A phase I multicenter study to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone in patients with resected solid tumors and in combination with pembrolizumab in patients with unresectable solid tumors. J Clin Oncol 37, 2019 (suppl; abstr 2523).</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【2】ANA Maria Arance Fernandez, Jean-Francois Baurain, Christof Vulsteke, Annemie Rutten, Ainara Soria, Javier Carrasco, Bart Neyns, Brenda De Keersmaecker, Tim Van Assche, Bertil Lindmark. A phase I study (E011-MEL) of a TriMix-based mRNA immunotherapy (ECI-006) in resected melanoma patients: Analysis of safety and immunogenicity. J Clin Oncol 37, 2019 (suppl; abstr 2641).</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【3】Gal Cafri, Jared J. Gartner, Kristen Hopson, Robert S. Meehan, Tal Z. Zaks, Paul Robbins, Steven A. Rosenberg. Immunogenicity and tolerability of personalized mRNA vaccine mRNA-4650 encoding defined neoantigens expressed by the autologous cancer. J Clin Oncol 37, 2019 (suppl; abstr 2643).</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【4】Juan Pablo Marquez-Manriquez, Pedro Alejandro Lucero-Diaz, Jose Antonio Matute-Briseno, Alejandro Camacho-Hernandez, Dolores Gallardo-Rincon. Effect of subcutaneous multipeptide active antigen-specific immunotherapy at lymph nodes and tumor sites on clinical outcomes in progressive tumors. J Clin Oncol 37, 2019 (suppl; abstr 2636).</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【5】Eniko Rita Toke, Mónika Megyesi, Levente Molnar, József Tóth, Orsolya Lőrincz, Sjoerd H. van der Burg, Marij Welters, Cornelis Joseph Melief, Wolfgang Schönharting, Sybille Urban, Tim Roehnisch, Uwe Heine, Eszter Somogyi, Zsolt Csiszovszki, Katalin Pántya, Péter Páles, István Miklós, Franco Lori, Julianna Lisziewicz. Prediction the clinical outcomes of cancer patients after peptide vaccination. J Clin Oncol 37, 2019 (suppl; abstr e14295).</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【6】Robert O. Dillman, Andrew N Cornforth, Edward Francis McClay, Carol DePriest. Survival by stage and tumor measurability in metastatic melanoma patients treated with autologous dendritic cell tumor cell vaccines. J Clin Oncol 37, 2019 (suppl; abstr 2637).</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【7】Hoyoung M. Maeng, Lauren Virginia Wood, Brittni Moore, Mohammadhadi H. Bagheri, Santhana Webb, Lee England, Giselle Martinez, Seth M. Steinberg, Svetlana Pack, David Stroncek, John Charles Morris, Masaki Terabe, Jay A. Berzofsky. Preliminary results of a phase I clinical trial using an autologous dendritic cell cancer vaccine targeting HER2 in patients with metastatic cancer or operated high-risk bladder cancer (NCT01730118). J Clin Oncol 37, 2019 (suppl; abstr 2639).</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【8】Sarah Schmidt, Weldy V. Bonilla, Mindaugas Pauzuolis, Andrea Reiter, Theresa Kleissner, Daniel Oeler, Felix Stemeseder, Ursula Berka, Bettina Kiefmann, Sophie Schulha, Igor Matushansky, Doron Merkler, Daniel Pinschewer, Klaus Karl Orlinger. Live-attenuated LCMV-based vector for active immunotherapy of HPV16+ cancer. J Clin Oncol 37, 2019 (suppl; abstr e14303).</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">【9】Klaus Karl Orlinger, Weldy V. Bonilla, Sandra M Kallert, Nicole Kirchhammer, Anna-Friederike Marx, Magdalena Krzyzaniak, Sarah Schmidt, Josipa Raguz, Ursula Berka, Stephan Guenther, Alfred Zippelius, Daniel Pinschewer. Arenavirus-based vector platform for massive tumor self-antigen-specific CD8 T cell immunity. J Clin Oncol 37, 2019 (suppl; abstr e14297).</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;"><strong style="color: blue;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_gif/vl8De1ZSQceN5Tpu3ib8LO7LCJyibSUdvpP7smHSE2mfT4VibcicxUN2O2WQqaV0Y1suUXFzOrWwLPX8mNiaMdI1ZYw/640?wx_fmt=gif&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1" style="width: 50%; margin-bottom: 20px;"></span></strong></span></strong></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">热门<span style="color: black;">举荐</span></span></strong></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><a style="color: black;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/vl8De1ZSQce3CTGnFtdx0MPiclnicGiaJeicpZuDPicTkxQla2zicGkbYeJs0yS6Xmd353rTE5aj1qy7xiapqL4Y0w6Wg/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"></span></a></p>
    <h2 style="color: black; text-align: left; margin-bottom: 10px;"><a style="color: black;"><span style="color: black;">屠呦呦的“青蒿素抗药性”最新<span style="color: black;">科研</span>，<span style="color: black;">到底</span>哪里“重大突破”了？</span></a></h2>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><a style="color: black;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/vl8De1ZSQce3CTGnFtdx0MPiclnicGiaJeicmSZMibUoK3EW5Ew2D7JxDWOJ17JEDaRGBnN9v6v9RebyQ104Aibbsicyw/640?wx_fmt=jpeg&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"></span></a></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><a style="color: black;">中国地震局<span style="color: black;">颁布</span> 最权威《地震逃生手册》</a></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;"><strong style="color: blue;"><span style="color: black;">扫码<img src="https://mmbiz.qpic.cn/mmbiz_png/vl8De1ZSQcf2QkABbuvpTW09Jk8SRhz8ibZxV4d9ubvX8sFGt7qDabXuxWib9VLaSGBVfQfIKEuxVJt7E6fnKmJA/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;">加康宝为好友，发送暗号”医学创新“，进入健康界<strong style="color: blue;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;">交流</span></strong></span></strong>群</span></strong></span></strong></span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/vl8De1ZSQcfvamYibtMgPt3JF7alG7xz4HA8PiaiaMqKrS1TWTSjNdKeT232icC86NAA0gQ5LZcqTwP4BS3fJIIwOA/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" 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;">&nbsp;&nbsp;版权声明&nbsp;&nbsp;</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">注：</span><span style="color: black;">转载仅分享，如有侵权请联系健康界。</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;">文案</span>转载，请关注<strong style="color: blue;">“健康界”</strong>公众号</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_gif/vl8De1ZSQcfNibOZTAicSzuGia2clk5ziaUGTMAhzCEsHoj5NwrSrBlFnx3LcCujwWk6Ecx14t8KJhW9OdfCmznXIw/640?wx_fmt=gif&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1" 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;">点击“</span><span style="color: black;">阅读原文</span><span style="color: black;">”，</span><span style="color: black;">下载健康界客户端，认证赢好礼！</span></p>
    <p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">百万医健人士，都在看<img src="https://mmbiz.qpic.cn/mmbiz_png/vl8De1ZSQcevvKnIrcQoA7kYIQOJiciaaC5m1pj6XOVCNr4cm97WAFK0wmZHbr3LEyKwVGsL09IClClJD3pcZFqA/640?wx_fmt=png&amp;tp=webp&amp;wxfrom=5&amp;wx_lazy=1&amp;wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>

zrd123 发表于 2024-8-29 15:14:07

软文发布平台 http://www.fok120.com/

m5k1umn 发表于 2024-9-5 07:11:50

楼主节操掉了，还不快捡起来！

wrjc1hod 发表于 2024-10-3 18:20:45

谷歌外贸网站优化技术。

1fy07h 发表于 2024-10-17 20:48:56

感谢楼主的分享！我学到了很多。

4lqedz 发表于 2024-10-19 13:58:11

哈哈、笑死我了、太搞笑了吧等。

j8typz 发表于 3 天前

我完全同意你的看法，期待我们能深入探讨这个问题。

查看完整版本: 抢先看！2019ASCO癌症疫苗最新发展