20241007|免疫疗法有望清除体内衰老细胞（上）

In 2010 an American girl called Emily Whitehead developed a form of leukaemia that is usually terminal. She was five years old.

2010年，一位名叫艾米丽·怀特黑德（Emily Whitehead）的美国女孩患上了一种通常是晚期的白血病。当时她只有五岁。

Two years later, she became the first paediatric patient to be offered a form of treatment called CAR-T, in which the body's immune system is reprogrammed to attack cancerous cells. The treatment worked.

两年后，她成为第一位接受CAR-T治疗的儿科患者，这种治疗方法可以重新编程人体的免疫系统来攻击癌细胞。这种治疗很有效。

A documentary film about her journey, released in 2022, was called "Of Medicine and Miracles".

一部关于她旅程的纪录片于2022年上映，名为Of Medicine and Miracles。

Researchers do not use the second of those m-words lightly. But CAR-T therapy seems to justify the excitement.

研究人员不会轻易使用Miracle这个词。但CAR-T疗法似乎证明了这种兴奋是合理的。

A decade on from Emily's treatment, its proponents are finding that the cells driving many other diseases, from asthma to heart conditions, share similarities with cancer cells that could allow them to be targeted in the same way.

在艾米丽接受治疗十年后，其支持者发现，驱动从哮喘到心脏病等许多其他疾病的细胞与癌细胞有相似之处，可以以同样的方式对它们进行靶向治疗。

Early results from clinical trials are encouraging. CAR-T therapy works because many harmful cells have specific protein markers called antigens on their surfaces.

临床试验的早期结果令人鼓舞。CAR-T疗法之所以有效，是因为许多有害细胞表面都有称为抗原的特定蛋白质标记。

T-cells in a patient's immune system are extracted, genetically tweaked to possess "chimeric antigen receptors" (the CARin CAR-T) that can spot these antigens, and then returned to the patient's body.

提取患者免疫系统中的T细胞，对其进行基因改造，使其拥有能够识别这些抗原的“嵌合抗原受体”（CAR-T中的CAR），然后将其送回患者体内。

Several CAR-T cell therapies licensed to treat leukaemia and lymphoma, for example, use T-cells engineered with CARs that can recognise a protein called CD19, which is found on the outside of those cancer cells.

例如，几种获准治疗白血病和淋巴瘤的CAR-T细胞疗法使用经过CAR改造的T细胞，这些T细胞可以识别一种名为CD19的蛋白质，这种蛋白质位于这些癌细胞的外部。

"When you hear CAR-T cell therapy you think cancer," says Scott Lowe, a researcher at the Memorial Sloan Kettering (MSK) Cancer Centre in New York.

“当你听到CAR-T细胞疗法时，你会想到癌症，”纽约纪念斯隆凯特琳癌症中心(MSK)研究员Scott Lowe说道。

"But what we're learning is that this approach of engineering immune cells to target disease has much broader possibilities."

“但我们了解到，这种改造免疫细胞以针对疾病的方法具有更广泛的可能性。”

Take asthma. Although medicines allow millions of people to control their symptoms, severe asthma attacks still kill three people in Britain every day.

以哮喘为例。尽管药物可以让数百万人控制症状，但严重的哮喘发作仍然每天在英国导致三人死亡。

That is often down to a misfiring immune system, which triggers what is called a type 2 inflammation response.

这通常是由于免疫系统失灵，从而引发所谓的2型炎症反应。

Intended as a defence against parasites, the body releases aggressive white blood cells called eosinophils which can cause inflammation in the airways, making it hard for people with severe asthma to breathe.

为了抵御寄生虫，人体会释放一种名为嗜酸性粒细胞的攻击性白细胞，这种细胞会引起呼吸道炎症，使患有严重哮喘的病人呼吸困难。

Asthma treatments, including inhaled steroids and injected antibodies, aim to lower the number of circulating eosinophils and so reduce inflammation and symptoms.

哮喘治疗，包括吸入类固醇和注射抗体，旨在降低循环嗜酸性粒细胞的数量，从而减轻炎症和症状。

Researchers in China have now shown that CAR-T cells can be engineered to do a more thorough job, at least in mice.

中国的研究人员现在已经证明，CAR-T细胞可以经过改造，至少在小鼠身上可以发挥更彻底的作用。

In a study published in May in Nature Immunology, they described how a single dose of the cells injected into animals bred to mimic the symptoms of asthma in effect cured them of the condition.

在5月份发表在《自然免疫学》杂志上的一项研究中，他们描述了如何将一剂细胞注射到模仿哮喘症状的动物体内，从而治愈哮喘。

The researchers could do this because they identified a distinctive antigen on the surface of the eosinophils: a receptor for the signalling molecule interleukin-5.

研究人员之所以能做到这一点，是因为他们发现了嗜酸性粒细胞表面的一种独特抗原：信号分子白细胞介素5的受体。

To design a therapy that could target eosinophils, the Chinese group, led by Peng Min at Tsinghua University in Beijing, added a CARprotein to the T-cell surface tailored to recognise this specific antigen.

为了设计一种可以针对嗜酸性粒细胞的疗法，由清华大学彭敏领导的中国研究小组在T细胞表面添加了一种专门用于识别这种特定抗原的CAR蛋白。

When the T-cells find a match, they release toxins that act to destroy the eosinophils, thereby dampening the body's inflammation response.

当T细胞找到匹配物时，它们会释放毒素来破坏嗜酸性粒细胞，从而抑制身体的炎症反应。

Dr Peng's team has already shown that anti-asthma human T-cells can be prepared in the same way. Some CAR-T cancer treatments have unintended consequences.

彭博士的团队已经证明，抗哮喘的人类T细胞可以用同样的方式制备。一些CAR-T癌症治疗会产生意想不到的后果。

The treatment that targets CD19 antigens, for example, can also attack the body's B-cells, which produce antibodies and maintain vital memory of immunity against pathogens.

例如，针对CD19抗原的治疗也可以攻击人体的B细胞，而B细胞会产生抗体并保持对病原体的重要免疫记忆。

But this need not be a disaster. In fact, some researchers now see this as a way to treat medical problems caused by overactive immune systems.

但这不一定是一场灾难。事实上，一些研究人员现在将此视为治疗由过度活跃的免疫系统引起的医疗问题的一种方法。

A series of small clinical trials have suggested that the licensed technique to produce CD19-directed T-cells can also help treat people with systemic lupus erythematosus (SLE), an autoimmune disease that attacks a person's own organs.

一系列小规模临床试验表明，获得许可的生产CD19定向T细胞的技术也可以帮助治疗系统性红斑狼疮患者，这是一种攻击人体自身器官的自身免疫性疾病。