生物与医学2022nature.com
癌症疫苗：下一代免疫疗法的前沿
Cancer vaccines: the next immunotherapy frontier
专业 · 约 55 分钟读完前置知识：肿瘤免疫学基础、疫苗学、临床试验设计
导读
这篇综述讨论癌症疫苗为何被视为免疫治疗的下一个前沿，梳理如何调动免疫系统识别和攻击肿瘤，以及该领域在临床转化中面临的挑战。文章回顾相关策略与经验，强调癌症疫苗仍有待验证的潜力。
HN 关注点：癌症疫苗能否真正落地并惠及大众，讨论焦点包括预防性药物的公众沟通、成本可及性、EBV 等潜伏感染，以及综述与其他免疫疗法开发史的比较是否公允。
HN 评论精选
这几条评论里：质疑 2 补充 2
补充预防性药物因效果不可见而难被公众感知，应少诉诸权威、多用人能懂的研究观察来沟通。
一种有时能阻止坏事发生的药物很难让人体会到价值：如果它起效，你永远不会知道；而且它可能还有副作用。我们需要加强公众教育，说明我们为何相信这些药物有效。我希望在社交媒体上展示研究：“我们给3万人用了这种药，你猜发生了什么！”少一些审查，多把研究以人们能理解的方式呈现。少诉诸权威，多诉诸观察；是的，你观察了你的两位亲戚，而我观察了3万人，你自己判断哪个更有说服力。大多数人不会读你的三段摘要，更不会读全文。你得用几句话告诉他们观察到了什么，最好尽量少加解释。
Buttons840查看英文原文
A medicine that sometimes stops a bad thing from happening is hard for people to appreciate, because if it works you'll never know it, and it might have some side effects. We need to improve public education about why we believe these medicines work. I want to see the studies presented on social media: "We gave 30,000 people this drug and you won't believe what happened!" Less censoring people and more presenting the studies in a way people can understand. Less appealing to authority and more appealing to observations; yes, you observed your 2 relatives, and I observed 30,000 people, judge for yourself which is more persuasive. Most people aren't going to read your 3 paragraph abstract, let alone the the full paper. You have to tell them the observations in a few sentences, preferably with minimal added interpretation.
补充希望癌症疫苗技术能变得可及并扩展到清除 EBV 等潜伏感染、改进普通疫苗，而非只做昂贵小众疗法。
我希望这项技术如果成功，不要停留在极其昂贵、小众的癌症疗法领域。例如 EBV 很麻烦，20岁以上的人很可能有潜伏感染。一种能清除现有 EBV 感染的安全疫苗，有可能预防一大类严重疾病，包括癌症和其他疾病。可以把它想成带状疱疹疫苗，但意义更大。也有意思的是，这些技术能否带来对普通急性病显著更好的疫苗。有证据表明，对新冠感染细胞生命周期早期表达的胞内抗原已有细胞免疫的人，具有很强免疫力。当前疫苗不提供这种免疫，而癌症疫苗大多靶向针对胞内抗原的细胞免疫。
amluto查看英文原文
I hope this technology, if successful, doesn’t get stuck in the land of very expensive, exotic cancer therapies. Epstein-Barr virus, for example, is nasty, and if you are over the age of 20 or so you probably have a latent EBV infection. A safe vaccine that could clear an existing EBV infection has the potential to prevent quite a large set of nasty conditions, cancer and otherwise. Think of it as something like the shingles vaccine, but a bigger deal. It with also be interesting to see if the technologies used could lead to dramatically better vaccines for ordinary acute conditions. There is some evidence that people with pre-existing cellular immunity to intercellular antigens expressed very early in the lifecycle of a Covid-infected cell confers very strong immunity. The current vaccines don’t provide this sort of immunity, but the cancer vaccines are mostly targeting cellular immunity to intracellular antigens.
质疑认为多数癌症源于生活方式/环境，预防应针对根本原因，而非依赖广谱式预防药物。
癌症本来就可预防，绝大多数癌症与生活方式/环境有关。这就像在超高密度笼养农场里给动物预防性使用广谱抗生素。如果不是把动物养在恶劣条件下，大多数抗生素根本不需要，而长期后果很严重。
lm28469查看英文原文
Cancer is already preventable, the vast majority of them are lifestyle/environment related: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515569/ This is like preventively giving broad spectrum antibiotics to animals raised in super dense cage farms. You wouldn't need most of them if you weren't raising them in hellish conditions, and the long term consequences are dire
质疑质疑综述用其他免疫疗法长期失败后成功来类比癌症疫苗不公允，疫苗技术更成熟、CAR-T更复杂。
“例如，许多单克隆抗体试验近20年未能显示可重复疗效，直到1997年利妥昔单抗成功；抗PD-1抗体数据多年缺乏临床疗效，直到首个nivolumab数据发表；CAR-T临床数据多年无效，才迎来最终成功。”这有点不诚实。提到的疗法是在那些时间段里从零开发的，而疫苗技术存在的时间已经超过其三倍。CAR-T也是比疫苗复杂困难得多的疗法……
Gatsky查看英文原文
> For instance, numerous monoclonal antibody trials failed to show reproducible efficacy for nearly 20 years before the eventual success of rituximab in 1997 (ref. 7); anti-programmed cell death protein 1 (PD-1) antibody data lacked clinical efficacy for years before the first nivolumab data were published8; and many years of ineffective chimeric antigen receptor T cell (CAR T cell) clinical data prefaced their eventual success. This is a bit disingenuous. The mentioned therapies were developed from scratch in those time frames, whereas vaccine technology has been around for over 3 times as long. CART cells are also a much more complex and difficult therapy than vaccines…
相关资源
从这篇论文所有 HN 讨论帖的全部评论里整理出来的链接。
历次讨论
- 2022Hacker News 讨论帖154 分 · 122 评
同领域还值得读
CRISPR 在活体动物中消除 HIV-1 感染
CRISPR eliminates HIV-1 infection in live animals
报告利用 CRISPR/Cas9 基因编辑技术在活体动物中清除 HIV-1 感染：研究人员通过腺病毒载体递送特定的 Cas9 系统，从被感染细胞中切除嵌入的 HIV 病毒 DNA。
生物与医学2017 · 1,455 分 · 239 评入门 · 约 30 分钟编辑精选保护区飞行昆虫生物量27年下降75%
75% decline over 27 years in total flying insect biomass in protected areas
这篇发表于 PLOS ONE 的研究通过在德国保护区长达 27 年的昆虫生物量监测，发现飞行昆虫总量下降了约 75%。
生物与医学2017 · 901 分 · 432 评入门 · 约 45 分钟编辑精选为什么大多数已发表的研究发现是错的
Why Most Published Research Findings Are False (2005)
这篇 2005 年发表于 PLOS Medicine 的经典论文由 John Ioannidis 撰写，论证了在统计功效不足、研究偏倚和多重检验等因素下，大多数已发表的医学研究发…
生物与医学2022 · 388 分 · 351 评入门 · 约 60 分钟编辑精选人类免疫系统的物理接线图
A physical wiring diagram for the human immune system
这篇 Nature 论文系统绘制了人类免疫系统的“物理接线图”：通过大规模实验鉴定免疫细胞表面受体之间的相互作用（包括约 30 种此前未知的受体互作），并结合定量计算模型模拟免疫…
生物与医学2022 · 342 分 · 49 评专业 · 约 90 分钟编辑精选脂肪组织在减重后仍保留肥胖的表观遗传记忆
Adipose tissue retains an epigenetic memory of obesity after weight loss
这篇 Nature 论文研究了肥胖对脂肪组织的长期影响：即使减重成功，脂肪细胞仍保留着肥胖时期的表观遗传记忆，可能解释为什么减重后容易反弹。
生物与医学2025 · 263 分 · 327 评进阶 · 约 45 分钟编辑精选