The 2024 American College of Rheumatology (ACR) annual meeting spotlighted transformative advancements in cell therapies for autoimmune diseases, with chimeric antigen receptor (CAR)-T therapies, T-cell engagers (TCEs), and multi-specific antibodies leading the charge.

2024年美国风湿病学会（ACR）年会聚焦了自身免疫性疾病细胞疗法的变革性进展，其中嵌合抗原受体（CAR）-T疗法，T细胞参与者（TCE）和多特异性抗体领先。

These innovations hold immense promise, but also come with challenges that demand further refinement. Here’s a closer look at some of the latest developments shared at ACR 2024.

这些创新具有巨大的前景，但也带来了需要进一步改进的挑战。以下是在2024年ACR上分享的一些最新发展。

CAR-T Therapy: A revolution in progress

Historically associated with haematologic cancers, CAR-T cell therapy is now making its way into the autoimmune landscape. At the forefront of discussions at ACR 2024 was the success of autologous CD19-directed CAR-T cell therapies in addressing B cell-mediated autoimmune diseases such as lupus and rheumatoid arthritis.

历史上与血液系统癌症相关的CAR-T细胞疗法现在正在进入自身免疫领域。ACR 2024讨论的最前沿是自体CD19指导的CAR-T细胞疗法在解决B细胞介导的自身免疫性疾病（如狼疮和类风湿性关节炎）方面的成功。

Data presented by companies like FATE, Cabaletta, and BMS highlighted how CAR-T therapy is reshaping treatment paradigms, offering durable remissions in severe autoimmune cases..

FATE，Cabaletta和BMS等公司提供的数据强调了CAR-T疗法如何重塑治疗范式，为严重的自身免疫病例提供持久的缓解。。

However, enthusiasm is tempered by discussions about key barriers. Experts at ACR 2024 noted that the requirement for apheresis to collect patient T-cells poses logistical and clinical challenges. Patients often need to taper immunosuppressants before cell collection, increasing the risk of disease flare-ups.

然而，关于关键障碍的讨论削弱了热情。ACR 2024的专家指出，单采血液采集患者T细胞的要求带来了后勤和临床挑战。患者通常需要在收集细胞之前减少免疫抑制剂，从而增加疾病爆发的风险。

Moreover, the quality of T-cells from autoimmune patients – already compromised by disease burden or chronic immunosuppressive therapy – can affect treatment efficacy..

此外，自身免疫患者的T细胞质量（已经受到疾病负担或慢性免疫抑制治疗的影响）可能会影响治疗效果。。

Allogeneic CAR-T therapies, highlighted by Allogene, Kyverna, and Caribou, are emerging as promising alternatives. These “off-the-shelf” solutions eliminate the need for apheresis, offer better batch control, and address some of the scalability and cost issues of autologous therapies.

由Allogene，Kyverna和Caribou强调的同种异体CAR-T疗法正在成为有前途的替代品。这些“现成”的解决方案消除了对单采血液的需求，提供了更好的批次控制，并解决了自体疗法的一些可扩展性和成本问题。

Despite the hurdles, the consensus is that CAR-T therapies represent a significant leap forward. For now, they are best suited for severe cases of autoimmune diseases, but advances in technology and accessibility could expand their application in the future.

尽管存在障碍，但共识是CAR-T疗法代表了一个重大的飞跃。。

T-Cell engagers and multi-specific antibodies: Precision immunomodulation

T细胞参与者和多特异性抗体：精确免疫调节

TCEs and multi-specific antibodies have also been spotlighted as complementary or alternative strategies to CAR-T therapies. These biologics offer a non-cellular approach to modulating the immune system and can be designed to target specific pathogenic pathways.

TCE和多特异性抗体也被视为CAR-T疗法的补充或替代策略。这些生物制剂提供了一种非细胞方法来调节免疫系统，可以设计为靶向特定的致病途径。

Unlike CAR-T therapies, TCEs are off-the-shelf biologics designed to harness the cytotoxic power of T-cells to selectively eliminate pathogenic immune cells. Their flexibility and ease of administration make them an attractive option, particularly in the outpatient setting.

与CAR-T疗法不同，TCE是现成的生物制剂，旨在利用T细胞的细胞毒性来选择性消除致病性免疫细胞。它们的灵活性和易于管理使其成为一个有吸引力的选择，特别是在门诊环境中。

Among the next-generation TCEs showing promise, Cullinan's CLN-978 stood out at ACR this year. This subcutaneous CD19/CD3-directed bispecific-TCE (BiTE) demonstrated deep B-cell depletion and a favourable safety profile with weekly injections in Phase 1 trials for non-Hodgkin’s lymphoma (NHL). Cullinan has since discontinued enrolment in its NHL study and will focus CLN-978’s development in autoimmune diseases; the BiTE is currently in Phase 1b development for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).

在显示出前景的下一代TCE中，Cullinan的CLN-978今年在ACR上脱颖而出。这种皮下CD19/CD3定向的双特异性TCE（BiTE）在非霍奇金淋巴瘤（NHL）的1期临床试验中显示出深度B细胞耗竭和良好的安全性，每周注射一次。此后，Cullinan停止了其NHL研究的入学，并将重点关注CLN-978在自身免疫性疾病中的发展；BiTE目前处于类风湿性关节炎（RA）和系统性红斑狼疮（SLE）的1b期发展阶段。

CLN-978 could represent a major step forward in reducing treatment burdens, offering patients a less invasive option with the potential for fewer clinic visits and greater convenience..

CLN-978可能代表着在减轻治疗负担方面迈出的重要一步，为患者提供了一种侵入性较小的选择，有可能减少诊所就诊次数，提供更大的便利。。

TCE’s advantages include bypassing the need for apheresis, shorter hospitalisation times, and the possibility of outpatient administration in the future. Additionally, TCEs allow for therapy interruption if severe adverse events (AEs) arise – a critical safety advantage over CAR-T therapies.

TCE的优势包括不需要单采血液，缩短住院时间，以及未来门诊管理的可能性。此外，如果出现严重不良事件（AE），TCE允许治疗中断-这是CAR-T治疗的关键安全优势。

However, questions remain about whether TCEs can match the magnitude and durability of efficacy observed with autologous CAR-T therapies.

然而，关于TCE是否可以与自体CAR-T疗法观察到的疗效的大小和持久性相匹配的问题仍然存在。

Challenges and future directions

挑战和未来方向

The enthusiasm for cell therapies is balanced by an acknowledgment of their current limitations:

Cost and accessibility: Autologous CAR-T therapies remain prohibitively expensive, limiting patient access and raising concerns about payer dynamics. Allogeneic CAR-Ts and TCEs, as scalable “off-the-shelf” solutions, could provide more affordable options.

成本和可及性：自体CAR-T疗法仍然昂贵，限制了患者的使用，并引起了对付款人动态的担忧。同种异体汽车Ts和TCE作为可扩展的“现成”解决方案，可以提供更实惠的选择。

Safety concerns: The reliance on lymphodepletive preconditioning and the broad immune suppression of many current therapies increase the risk of infections and other adverse effects.

安全问题：依赖淋巴清除预处理和许多当前疗法的广泛免疫抑制会增加感染和其他不良反应的风险。

Precision targeting: Most therapies, including CD19 CAR-T, indiscriminately target entire B-cell populations. The future lies in selectively targeting pathogenic cells, reducing collateral damage to the immune system.

精确靶向：大多数疗法，包括CD19 CAR-T，不加区别地靶向整个B细胞群。未来在于选择性靶向致病细胞，减少对免疫系统的附带损害。

Looking ahead, next-generation therapies that eliminate the need for lymphodepletion, improve specificity, and lower costs could expand the addressable patient population. Innovations like allogeneic CAR-T, TCEs, and bispecific antibodies represent promising steps in this direction. While not discussed at ACR 2024, Roche’s recent acquisition of Poseida Therapeutics adds another layer of optimism to the cell therapy landscape.

。同种异体CAR-T，TCE和双特异性抗体等创新代表了这一方向的有希望的步骤。虽然在2024年ACR上没有讨论，但罗氏最近收购波塞达治疗公司为细胞治疗领域增添了另一层乐观情绪。

Poseida’s gene-editing and cell therapy platforms, including their next-generation CAR-T technologies, are poised to accelerate the development of innovative treatments for both oncology and autoimmune diseases. This move underscores the pharmaceutical industry’s belief in the transformative potential of cell-based therapies..

波塞达的基因编辑和细胞治疗平台，包括其下一代CAR-T技术，有望加速肿瘤和自身免疫性疾病创新治疗的发展。这一举措突显了制药行业对基于细胞的疗法的变革潜力的信念。。

Conclusion

结论

ACR 2024 highlighted a pivotal moment in autoimmune disease therapy, with CAR-T, TCEs, and multi-specific antibodies offering hope for transformative treatments. As these therapies evolve, they hold the potential to not just manage, but fundamentally alter the course of autoimmune diseases, bringing hope to millions of patients worldwide..

ACR 2024突出了自身免疫性疾病治疗的关键时刻，CAR-T，TCE和多特异性抗体为转化治疗提供了希望。随着这些疗法的发展，它们不仅具有管理的潜力，而且可以从根本上改变自身免疫性疾病的进程，为全球数百万患者带来希望。。

About the authors

关于作者

Paola Pinto is a consultant at Lifescience Dynamics, specialising in pharmaceutical insights and strategy, with a focused expertise and interest in autoimmune diseases, including rheumatology, dermatology, and gastroenterology. Experienced in partnering with global pharmaceutical clients throughout the drug development pipeline, from candidate selection to life cycle management, she is keen to understand and deliver insights on the dynamic treatment landscapes across therapeutic areas, including the emergence of novel modalities such as cell therapies.

Paola Pinto是Lifescience Dynamics的顾问，专门研究药物见解和策略，专注于自身免疫性疾病，包括风湿病，皮肤病和肠胃病。在整个药物开发流程中，从候选人选择到生命周期管理，她都有与全球制药客户合作的经验，她渴望了解并提供有关治疗领域动态治疗景观的见解，包括细胞疗法等新型模式的出现。

Before joining Lifescience Dynamics, Pinto completed a PhD in Molecular Biology and Biochemistry at the University of Vienna..

在加入生命科学动力学之前，平托在维也纳大学完成了分子生物学和生物化学博士学位。。

Stylianos Sarrigiannidis is a senior business analyst with Lifescience Dynamics, exercising his expertise in cutting-edge developments across autoimmune diseases like SLE and cell therapies such as CAR-Ts. He endeavors to provide strategic insights to advance innovation and study patient outcomes in these transformative fields.

Stylianos Sarrigiannidis是Lifescience Dynamics的高级商业分析师，他在SLE等自身免疫性疾病和CAR-Ts等细胞疗法的前沿发展方面发挥了专业技能。他努力提供战略见解，以推动创新并研究这些变革领域的患者结果。

Before joining Lifescience Dynamics, Sarrigiannidis earned a PhD in Biomedical Engineering at the University of Glasgow, where he focused on drug delivery mechanisms, tissue regeneration, and biomaterials..

在加入Lifescience Dynamics之前，Sarrigiannidis在格拉斯哥大学获得了生物医学工程博士学位，专注于药物输送机制，组织再生和生物材料。。

Callum McCarthy is a business analyst with Lifescience Dynamics. He is actively supporting a variety of projects across immunology indications, including autoimmune diseases such as lupus and rheumatoid arthritis, with a focus on innovative therapies like CAR-T cell therapies, and bispecific antibodies.

Callum McCarthy是Lifescience Dynamics的商业分析师。他积极支持各种免疫学适应症的项目，包括狼疮和类风湿性关节炎等自身免疫性疾病，重点关注CAR-T细胞疗法和双特异性抗体等创新疗法。

Prior to joining Lifescience Dynamics, McCarthy earned a PhD in Clinical Medicine Research (Infectious Disease) from Imperial College London, where he investigated molecular pathways involved in inflammatory cell responses to bacterial infections. He also holds a Master's degree in Biological Science from the University of Warwick..

。他还拥有华威大学生物科学硕士学位。。