A revolutionary cancer treatment could transform autoimmune disease
A revolutionary cancer treatment could transform autoimmune disease
一种革命性的癌症疗法可能会改变自身免疫性疾病的治疗
At age 49, Jan Janisch-Hanzlik’s multiple sclerosis was destroying her freedom to live the life she wanted. She gave up her active nursing job for a desk role. Frequent falls made her afraid to carry her grandchildren. She had to move to a bigger house to make room for the wheelchair she feared she might end up needing full-time. Even the best available medication wasn’t improving Janisch-Hanzlik’s symptoms, and she worried they’d only get worse. So when she learned about a trial of CAR T cell therapy at the University of Nebraska Medical Center in Omaha, close to the city of Blair where she lives, she phoned the clinic every other month until they were ready to enroll her as the first patient.
49 岁的简·亚尼什-汉兹利克（Jan Janisch-Hanzlik）患有多发性硬化症，这剥夺了她过上理想生活的自由。她不得不放弃了活跃的护理工作，转而从事文职。频繁的跌倒让她不敢抱自己的孙辈。她不得不搬进一所更大的房子，为她担心未来可能需要全职使用的轮椅腾出空间。即使是目前最好的药物也无法改善她的症状，她担心病情只会恶化。因此，当她得知位于奥马哈的内布拉斯加大学医学中心（University of Nebraska Medical Center）正在进行一项 CAR T 细胞疗法试验时，她每隔一个月就给诊所打电话，直到他们准备好将她作为首位患者招募入组。
Originally designed to target and wipe out cancer by reprogramming the patient’s immune cells, CAR T is now being offered to patients in hundreds of clinical trials for autoimmune conditions like multiple sclerosis, lupus, Graves’ disease, vasculitis, and many others. The hope is that CAR T can duplicate the success it has demonstrated in a range of blood cancers by hunting down and eliminating cells that target the self in autoimmune diseases. This would essentially reset the body’s defenses to a state like the one that existed before the disease took hold.
CAR T 疗法最初旨在通过重编程患者的免疫细胞来靶向并消灭癌症，目前正被用于数百项临床试验中，旨在治疗多发性硬化症、狼疮、格雷夫斯病、血管炎等多种自身免疫性疾病。人们希望 CAR T 能够复制其在多种血癌中展现出的成功，通过搜寻并清除自身免疫性疾病中攻击机体自身的细胞。这本质上是将人体的防御系统重置到疾病发作前的状态。
But along with CAR T’s promise come risks, questions, and challenges. There’s uncertainty about how well it will work for autoimmunity and how long any benefits might last, as well as what long-term side effects might arise. Janisch-Hanzlik knew this when she sat down to receive the experimental treatment on June 9, 2025; she felt a mix of hope and fear knowing that she would be spending the next week being monitored for side effects including dangerous inflammation.
然而，CAR T 在带来希望的同时，也伴随着风险、疑问和挑战。目前尚不确定它对自身免疫性疾病的疗效如何，疗效能持续多久，以及可能会出现哪些长期副作用。2025 年 6 月 9 日，当亚尼什-汉兹利克坐下来接受这项实验性治疗时，她深知这一点；她感到既充满希望又心怀恐惧，因为她知道接下来的一个星期里，她将接受严密监测，以防出现包括危险炎症在内的副作用。
In addition to her clinical expertise and desire to pioneer a new treatment, Janisch-Hanzlik’s two young grandchildren helped inspire her pursuit of a treatment with known risks and uncertain benefits. Because multiple sclerosis has a genetic component, Janisch-Hanzlik knew that they have an elevated chance of going through the same struggle she has. “I would want to be able to say I did everything that I possibly could to prevent them, or anyone else, from having something like this,” she says.
除了凭借自身的临床专业知识和尝试新疗法的愿望外，亚尼什-汉兹利克的两个年幼孙辈也激励她去追求这种风险已知但获益尚不确定的治疗。由于多发性硬化症具有遗传因素，亚尼什-汉兹利克知道她的孙辈患上同样疾病的几率更高。“我希望能够说，我已经尽我所能去阻止他们或其他人遭受这样的痛苦，”她说。
From cancer to autoimmunity
从癌症到自身免疫
The first CAR T cancer treatment was approved by the Food and Drug Administration in 2017 for an aggressive form of leukemia. Since then, the powerful and intensive treatment has resulted in long-term remission for many cancer patients. The basic premise of CAR T is to activate the power of key immune cells called T cells. T cells normally recognize other cells that have been infected by a virus or bacterium, or are otherwise abnormal, and either destroy them or recruit other parts of the immune system to do so.
首个 CAR T 癌症疗法于 2017 年获得美国食品药品监督管理局（FDA）批准，用于治疗一种侵袭性白血病。自那时起，这种强效且密集的治疗已使许多癌症患者实现了长期缓解。CAR T 的基本前提是激活被称为 T 细胞的关键免疫细胞的力量。T 细胞通常能识别被病毒或细菌感染的细胞，或以其他方式异常的细胞，并将其摧毁，或招募免疫系统的其他部分来完成这一任务。
In CAR T for cancer, scientists engineer those T cells to specifically hunt and destroy malignant cells. The technology got its start when cancer researchers figured out how to take out a patient’s own T cells, insert DNA instructions for a “chimeric antigen receptor,” or CAR, and put them back into the person’s circulation. The CAR, which sits on the T cell’s surface and latches on to a specific molecular partner on the surface of cancerous cells, activates the T cell to attack.
在用于癌症的 CAR T 疗法中，科学家通过工程化改造这些 T 细胞，使其能够专门搜寻并摧毁恶性细胞。这项技术始于癌症研究人员发现如何提取患者自身的 T 细胞，植入“嵌合抗原受体”（CAR）的 DNA 指令，然后再将其输回患者的血液循环中。CAR 位于 T 细胞表面，能够锁定癌细胞表面的特定分子伴侣，从而激活 T 细胞进行攻击。
Today CAR T cells are most commonly programmed to attack B cells, another key immune player. B cells are normally responsible for making antibodies, but in certain blood cancers, they proliferate out of control. By giving T cells a CAR that recognizes one of a couple of molecules unique to the B cell surface, the cells are reprogrammed to find and eliminate those cancerous cells. B cells also are the central problem in many autoimmune conditions: They mistakenly make antibodies against normal tissues instead of against invading pathogens.
如今，CAR T 细胞最常被编程用于攻击 B 细胞，这是另一个关键的免疫参与者。B 细胞通常负责制造抗体，但在某些血癌中，它们会失控增殖。通过赋予 T 细胞一种能够识别 B 细胞表面特有分子的 CAR，这些细胞被重新编程以寻找并消除那些癌细胞。B 细胞也是许多自身免疫性疾病的核心问题：它们错误地针对正常组织而非入侵的病原体制造抗体。
So as CAR T began to succeed against B cell cancers, it didn’t take long for doctors to reason that CAR T therapy might also be able to wipe out bad B cells in people with autoimmunity. There are many variations on CAR T procedures, but the basic process involves removing, modifying, and reinfusing patient T cells so they can attack their target, which is B cells in the case of autoimmune disease.
因此，随着 CAR T 在治疗 B 细胞癌症方面取得成功，医生们很快推断出 CAR T 疗法或许也能清除自身免疫性疾病患者体内的“坏”B 细胞。CAR T 手术有许多变体，但基本过程包括提取、改造并重新输注患者的 T 细胞，使其能够攻击目标——在自身免疫性疾病中，这个目标就是 B 细胞。
A German team pioneered autoimmune CAR T in a woman with lupus, reporting positive results in 2021. Since then, that team and others have worked to translate the oncology success of CAR T to tackle a broad spectrum of autoimmune diseases. “I think it’s a game changer,” says Amanda Piquet, an autoimmune neurologist at the University of Colorado Anschutz in Aurora.
2021 年，一个德国团队率先在一名狼疮女性患者身上应用了自身免疫 CAR T 疗法，并报告了积极的结果。自那时起，该团队和其他研究人员一直致力于将 CAR T 在肿瘤学上的成功转化为治疗广泛自身免疫性疾病的手段。“我认为这是一个改变游戏规则的疗法，”奥罗拉科罗拉多大学安舒茨医学校区（University of Colorado Anschutz）的自身免疫神经学家阿曼达·皮奎特（Amanda Piquet）说。
Piquet is evaluating CAR T therapy for a rare and poorly understood autoimmune condition called stiff person syndrome, with symptoms including muscle stiffness and painful spasms. There is no FDA-approved treatment. When she heard about a company called Kyverna that was testing CAR T cell therapy in the syndrome, she thought it was “a perfect opportunity.” The study she led, which reported preliminary results in December 2025, tested a single dose of CAR T in 26 people. Before the treatment, many participants struggled with a slow, mechanical gait, and 12 used assistive devices such as walkers and canes. Most patients were able to walk faster by 16 weeks post-treatment, and eight no longer needed their assistive devices for short distances. In April, the company reported that all 26 patients, as of their last follow-up appointment four to 12 months out from the therapy, were no longer using any other immunotherapies.
皮奎特正在评估 CAR T 疗法对一种罕见且知之甚少的自身免疫性疾病——僵人综合征（stiff person syndrome）的疗效，该病的症状包括肌肉僵硬和疼痛性痉挛。目前尚无 FDA 批准的治疗方法。当她听说一家名为 Kyverna 的公司正在测试针对该综合征的 CAR T 细胞疗法时，她认为这是一个“绝佳的机会”。她领导的研究在 2025 年 12 月报告了初步结果，测试了 26 名患者单剂量的 CAR T 治疗。治疗前，许多参与者步态缓慢、僵硬，12 人使用助行器或拐杖等辅助设备。治疗 16 周后，大多数患者能够走得更快，8 人在短距离行走时不再需要辅助设备。4 月份，该公司报告称，截至治疗后 4 到 12 个月的最后一次随访，所有 26 名患者均已停止使用任何其他免疫疗法。
Risks and uncertainties
风险与不确定性
Despite such striking results, reprogramming the imm… 尽管取得了如此惊人的成果，但重编程免疫系统……