来源：《新科学家》
原文见刊日期：2023年2月4日
One of the most amazing things about the immune system is how hard it works without you even being aware. It not only fights off bacteria and viruses every day, it also kills off most cancers long before they become a threat. But sometimes cancers manage to dodge the immune system – and a number of cancer therapies rely on restoring its effectiveness. An emerging star is CAR T-cell therapy, which has produced dramatic results for some cancers when all the usual treatments have failed.
免疫系统最神奇的地方之一是它在你不知不觉中工作得多么努力。它不仅每天都与细菌和病毒作斗争，还能在大多数癌细胞形成威胁之前就将它们杀死。但有时癌细胞能够避开免疫系统——许多癌症疗法依赖于恢复免疫系统的有效性。一颗冉冉升起的明星是CAR-T细胞疗法，当所有常规疗法都失败时，这种疗法对某些癌症产生了显著的效果。
This incredible technology relies on T-cells, immune cells that patrol our body, killing infected or cancerous cells. T-cells detect their targets with a receptor that protrudes from their surface and binds to a target protein, or a displayed fragment of a protein, on the outside of other cells. What this means is that if you add the right receptor to T-cells, you can make them target anything you want, including a cancer.
这项令人难以置信的技术依赖于T细胞，这是一种免疫细胞，可以在我们的身体中巡逻，杀死受感染或癌变的细胞。T细胞通过一种从其表面突出并与其他细胞外部的靶蛋白或露出的蛋白片段结合的受体来检测其目标。这意味着，如果你给T细胞添加正确的受体，你可以让它们攻击你想要的任何目标，包括癌细胞。
To achieve this, a person’s own T-cells are extracted and genetically modified to express a “chimeric antigen receptor”. This artificial receptor is made up of three proteins, one that recognises the cancer cell target and two that boost the T-cells’ activity.
为了实现这一点，患者自己的T细胞被提取出来并进行基因修饰，以表达“嵌合抗原受体”。这种人工受体由三种蛋白质组成，一种识别癌症细胞靶点，另两种增强T细胞活性。
Doctors multiply these cells and return them to their owner, where they seek out and destroy cells that have the target protein.
医生繁殖这些细胞，然后把它们交还给它们的主人，在那里它们会寻找并摧毁含有目标蛋白质的细胞。
With a few of the first people treated still remaining free of cancer a decade later, it can now be said that, in some cases, CAR T-cell therapies can cure advanced cancers.
在第一批接受治疗的患者中，有少数人在十年后仍然没有癌症复发，现在可以说，在某些情况下，CAR-T细胞疗法可以治愈晚期癌症。
Unfortunately, this approach isn’t a magic bullet. For starters, the immune attack on cancer cells it prompts can trigger potentially fatal side effects. What’s more, CAR T-cells only work against blood cancers, not solid tumours, and only in a minority of people.
不幸的是，这种方法并非灵丹妙药。首先，它引发的对癌症细胞的免疫攻击可能引发潜在的致命副作用。更重要的是，CAR-T细胞只对血癌有效，而对实体瘤无效，而且只对少数人有效。
But there is hope. The technique is being improved. One big issue is that having to use each individual’s own T-cells is extremely expensive, and with very ill people, it isn’t always possible to extract enough T-cells. Donor T-cells see every cell in the recipient’s body as foreign and start attacking them.
但还是有希望的。这项技术正在改进中。一个大问题是，必须使用每个人自己的T细胞是非常昂贵的，而且对于病情严重的人来说，提取足够的T细胞并不总是可能的。捐赠者T细胞视受者体内的每一个细胞为外来细胞，并开始攻击它们。
So, gene editing is now being used to knock out the genes involved in recognising cells as foreign, in addition to adding the receptor. These universal CAR T-cells can be used to treat many different people with the same cancers.
因此，除了添加受体外，基因编辑现在还被用于敲除参与识别外来细胞的基因。这些通用的CAR-T细胞可用于治疗许多患有相同癌症的不同人群。