How to beat rogue antibodies at their own game [Sponsored]

几乎我们每个人都认识患有自身免疫性疾病的人。

Almost all of us know someone who suffers from an autoimmune disease.

或者也许你自己就有。

Or maybe you do yourself.

自身免疫性疾病很常见。

Autoimmune diseases are common.

只有癌症和心血管疾病比它更普遍。

Only cancer and cardiovascular diseases are more prevalent.

那么，当身体与自己对抗时，你该如何应对呢？

So how do you fight a body that is fighting against itself?

Argenx，一家开发基于抗体的疗法的免疫学创新公司，正在开发一套新的分子工具，可以抑制免疫系统中叛逆的部分。

Argenx, an immunology innovation company that develops antibody based therapies, is developing a new toolkit of molecules that can tamp down the rebelling part of the immune system.

《科学美国人》定制媒体最近采访了Argenx的新任CEO凯伦·梅西，谈论了这套工具包含什么以及它如何帮助患者。

Scientific American Custom Media recently talked to argenx's new CEO, Karen Massey, about what's in the toolkit and how it's helping patients.

凯伦·梅西，非常感谢你加入我们。

Karen Massey, thank you so much for joining us.

我听说你和你的同事们自称是“argenx”。

I've heard that you and your colleagues call yourselves argenx.

你能解释一下为什么你们这样称呼自己，以及作为argenx的领导者，你们带来了什么？

Can you explain why you folks call yourselves that, and what you bring to the table as the lead argenx?

是的，当然可以。

Yeah, absolutely.

实际上，阿尔戈英雄的故事启发了我们的联合创始人，他们把公司命名为argenx，所以我们自称是阿尔戈英雄。

The story of the Argonauts actually is what inspired our co founders of argenx to call our company argenx, and therefore we call ourselves Argonauts.

阿尔戈英雄的故事讲的就是一群人团结合作，完成看似不可能的事情。

It's a the story of the Argonauts is all about a team of people working together to achieve the unthinkable.

所以我们的使命是为患者带来变革性的药物。

So we see our mission as bringing transformative medicines to patients.

我们相信，只有团队合作，拥有大胆的雄心，即使看起来不可能，只要我们齐心协力，就能为患者实现这一使命。

And we believe the only way that we can do that is by working together as a team, having this big, bold ambition, even when it seems impossible that if we work together, we'll be able to deliver that mission for patients.

从我个人的角度来看，作为公司的新任CEO，我和所有阿尔戈英雄同舟共济，我会卷起袖子，尽我所能推动创新思维，确保我们保持好奇心，保持勇气，大胆思考，挑战现状，真正发现新的科学、新的生物学，为患者带来变革性的结果。

And from my perspective, as I step into this new role as CEO of the company, I'm in the boat with all of those argenx, and I'm rolling up my sleeves and doing as much as I can to push out innovation in our thinking, to make sure we're staying curious, make sure that we're staying courageous and thinking big, challenging the status quo, and really uncovering new cool science, new biology that can deliver transformative outcomes for patients.

我知道argenx的专业领域是免疫系统。

I know argenx's expertise is the immune system.

我们体内都有一支免疫蛋白大军，用来抵御外来入侵者。

We've all got this army of immune proteins within us that fight off invaders.

比如，免疫球蛋白G，也就是IgG，在保护身体免受细菌、病毒和癌症侵害方面发挥着作用。

For example, immunoglobulin G, or IgG, plays a role in protecting the body from bacteria, viruses, and cancer.

但是当IgG攻击正常组织时，就会引发自身免疫性疾病。

But when IgGs form to attack normal tissue, you get an autoimmune disease.

我知道argenx正在开发一些新疗法来治疗自身免疫性疾病。

I know argenx is developing some new therapies to treat autoimmune diseases.

我觉得你们的方法特别有意思的一点是，你们把IgG以及与之相互作用的整个系统几乎看作一个药物工具箱。

One thing I find really fascinating about your approach is that you're looking at IgGs and the whole system that interacts with IgGs almost like a drug toolkit.

是的，完全正确。

Yeah, absolutely.

我自己不是科学家，但当我了解到免疫系统运作的各种细节时，我觉得非常着迷。

So I'm not a scientist myself, and I find it fascinating when I learn all the intricacies of how the immune system works.

这非常复杂。

It's incredibly complicated.

确实如此。

Indeed it is.

但作为公司的负责人，你必须确保你的科学家们拥有所需的资源和指导。

Yet you, as the head of the company, have to be sure your scientists have the resources and guidance they need.

你现在关注的重点是什么？

What are you focusing on right now?

我们正在努力寻找真正精准的方法，在免疫系统出错时进行纠正，并利用免疫系统的组成部分来帮助我们实现这一目标。

What we're working on is figuring out what are really targeted and precise ways that we can correct when when the system goes awry, leveraging components of the immune system to help us to do that.

因此，通过FcRn，我们可以利用免疫系统中清除这些自身抗体的部分，借助人体自身的自然清除机制。

And so certainly with the FcRn, what it allows us to do is use the part of the immune system that removes these autoantibodies from the body using the kind of natural removal system that the body has.

FcRn代表新生儿Fc受体。

FcRn stands for neonatal Fc receptor.

正常情况下，FcRn与IgG分子结合，保护它不被破坏。

Normally, FcRn binds to an IgG molecule and protects it from being destroyed.

如果你想让IgG蛋白留在体内对抗感染或癌症，那是有道理的。

That makes sense if you want to keep IgG proteins around to fight infections or cancer.

但如果你想清除那些攻击身体自身的IgG，那你可能想要阻断FcRn，对吧？

But if you want to get rid of IgGs that are attacking the body itself, then you probably want to block FcRn, right?

是的，FcRn有点像一种运输系统。

Yeah, so FcRn is sort of a transportation system.

我们做的事情是，比如说，劫持FcRn系统，把自身抗体拉过去，进入所谓的垃圾清除系统，这样那些惹麻烦的自身抗体——也就是免疫系统出错——就会被拉过去处理掉，这样它们就不能造成伤害了。

What we do is we, let's say, hijack that FcRn system to be able to pull autoantibodies across, go into, let's say, the trash removal system so that those autoantibodies that are causing the trouble, that's the immune system gone awry, they get pulled across and disposed of, so they can't do harm.

我喜欢这个，一个垃圾处理服务。

I like that, a trash disposal service.

Argenx把一种抗FcRn变成了药物，来加速垃圾处理。

Argenx turned an anti FcRn into a drug to speed up trash disposal.

Argenx的药物不是从细胞外面捡起自身免疫性IgG然后毫发无损地吐出来，而是引导那些捣乱的IgG进入细胞的垃圾压实机——溶酶体——进行销毁。

Instead of picking up an autoimmune IgG from the outside of the cell and spitting it out unharmed, argenx's drug guides the rogue IgG to the cell's garbage compactor, the lysosome, for destruction.

没错。

Exactly.

可以

Can

你能带我们了解一下从想法到实际被普通人使用的疗法，这个发现过程是怎样的吗？

you guide us down the path a discovery takes from an idea in someone's head to a therapy that's actually used by everyday people?

argenx是怎么做到的？

How does argenx get there?

对。

Yeah.

我觉得这是我们行业最酷的部分之一，尤其是我们在argenx的做法。

I think this is one of the coolest parts of our industry, but in particular how we do it at argenx.

我们不会假设只有我们的科学家才有所有答案或知道所有问题的解决方案。

We don't assume that just our scientists have all the answers or know all of the solutions to these problems.

他们会和其他科学家交流，这就是我们所说的共同创造，从“嘿，我们发现了这个可能想研究的目标”开始。

They're out engaging with other scientists and really what we call co creating, taking it from, hey.

到如何创造一种分子，可以阻断、激活、清除或做我们认为需要做的事情，实际上在实验室里物理构建那个分子。

We've identified this target that we might wanna look at to how do we create a molecule that can either block or activate or sweep or do whatever we think needs to be done, actually physically build that molecule in the lab.

然后我们继续合作，把它带给患者。

And then we continue to collaborate to bring it to patients.

所以一旦通过了安全性研究，我们就和治疗这些患者的临床医生合作。

So once it's gone through safety studies, then we collaborate with clinicians who are treating these patients.

我们该如何设计临床试验？

How should we design the clinical trial?

我们如何确保在最关键的指标上证明有效性和安全性？

How do we make sure that we're proving efficacy or safety on the most important parameters?

我们听取患者的意见，确保我们关注对患者最重要的事情。

We get patient input so that we make sure that we're focused on what's most important to patients.

那这个过程通常需要多长时间？

And how long does that process take typically?

很多很多年。

Many, many, many years.

从想法诞生到患者用上药，可能需要十年，这取决于生物学的创新程度、复杂程度以及研发路径。

From the inception of an idea to the patient getting the medicine can be a decade depending on how novel the biology is, how complicated it is, and what the pathway is.

你们是怎么决定投资哪些研究项目的？

How do you pick what research projects to invest in?

对。

Yeah.

首先，我想说我们所有的项目都是为了解决未被满足的需求。

First of all, I would say all of our programs are aimed at addressing unmet needs.

我们有一个非常严谨的流程来选择要针对的适应症。

We use a really rigorous process for selecting which indications we want to target.

我们是否了解生物学机制，并且有生物学上的依据？

Do we understand the biology and is there a biology rationale?

我们能否在这种适应症中开发这种分子？

Can we develop this molecule in this indication?

有没有明确的终点指标？

Are there endpoints?

有没有监管路径？

Is there a regulatory pathway?

但真正重要的是，是否存在未满足的患者需求？

But really importantly, is there an unmet patient need?

我们必须满足这第三个标准才能继续推进。

We have to meet that third criteria in order to move forward.

在argenx正在进行的众多项目中，你现在最期待哪一个？

Of everything that argenx is working on, what are you most excited about right now?

嗯，我们手头有很多项目，要选一个最喜欢的总是很难，因为正在进行的研究中有太多令人兴奋的科学发现。

Well, we are working on a lot and it's always hard to choose the favorite because there's so much exciting science that's ongoing.

当然，从我的角度来看，最让我兴奋的是我们的科学家不断发现和揭示这些新见解，真正深入研究免疫系统和免疫反应的基础组成部分，并找到那些可以精准干预的位点。

Certainly from my perspective, what I'm most excited about is how our scientists continue to identify and uncover these new insights, really look at the foundational components of the immune system and of our immune response, and look at these places where we can intervene that are very targeted.

但同时，通过靶向这些位点，可以影响许多不同的疾病。

But at the same time, by targeting them, can impact many different diseases.

所以这就是我觉得最令人兴奋的地方。

So that's what I find most exciting.

感谢你参加我们的节目。

Thank you for joining us.

Karen Massey是argenx公司的首席执行官，该公司致力于帮助改善罕见自身免疫性疾病患者的生活。

Karen Massey is the CEO of argenx, a company committed to helping improve the lives of people with rare autoimmune diseases.

本播客由《科学美国人》定制媒体制作，并得到了argenx的支持。

This podcast was produced by Scientific American Custom Media and made possible through the support of argenx.

感谢您的收听。

Thank you for listening.

我是《科学美国人》定制媒体的Aileen Ogengrund。

For Scientific American Custom Media, I'm Aileen Ogengrund.