Prednisone

The FDA has approved Johnson & Johnson's anti-FcRn antibody, nipocalimab, for the treatment of generalized myasthenia gravis. The drug will be sold under the brand name IMAAVY. This approval positions J&J to challenge leading competitors in the myasthenia gravis market, such as AstraZeneca, which markets the monoclonal antibodies SOLIRIS and ULTOMIRIS. J&J will also be competing with Argenx's VYVGART and UCB's RYSTIGGO and ZILBRYSQ. LAS VEGAS, May 22, 2025 /PRNewswire/ -- Myasthenia gravis is an autoimmune disorder in which antibodies disrupt the communication between nerves and muscles, resulting in skeletal muscle weakness. This weakness primarily affects voluntary muscles that control eye movement, facial expression, swallowing, and limb function. The condition is predominantly driven by autoantibodies targeting either the acetylcholine receptor (AChR-Ab) or a receptor-associated protein known as muscle-specific tyrosine kinase (MuSK-Ab). According to DelveInsight's analysis, there were approximately 300,000 diagnosed prevalent cases of myasthenia gravis across the 7MM in 2024. This number is expected to grow steadily over the forecast period (2025–2034), with a projected CAGR. The current myasthenia gravis therapeutics market mainly consists of symptomatic treatments such as acetylcholinesterase inhibitors like Mestinon. However, achieving full clinical remission with symptomatic therapy alone is challenging. As a result, immunosuppressive drugs are frequently introduced. First-line immunotherapy typically involves high-dose oral corticosteroids such as prednisone or prednisolone, which can induce a rapid response within 2 to 4 weeks. To reduce reliance on steroids and improve long-term disease control, nonsteroidal immunosuppressants (NSISTs) are often used. These include antimetabolites (e.g., azathioprine, mycophenolate mofetil, methotrexate, and cyclophosphamide) and calcineurin inhibitors (e.g., tacrolimus and cyclosporine). While NSISTs may be used as standalone treatments, they usually take 6 to 9 months to produce noticeable effects. Immunomodulatory therapies, including intravenous immunoglobulin (IVIg) and plasmapheresis (PLEX), are typically reserved for acute exacerbations or myasthenic crises. They are also employed as chronic treatments in patients who cannot tolerate or do not respond to standard immunosuppressants. Although traditional immunosuppressive strategies can help manage symptoms, achieving long-term, stable remission remains difficult. Additionally, about 15% of patients are considered treatment-refractory, meaning they either fail to respond to or cannot tolerate multiple immunosuppressive options. These patients often face the dual challenge of persistent symptoms and the adverse effects of long-term immunosuppression. Learn more about the myasthenia gravis disease market @ Myasthenia Gravis Treatment Medications The myasthenia gravis treatment market is well-established, with multiple approved drugs for myasthenia gravis, including SOLIRIS, ULTOMIRIS, RYSTIGGO, ZILBRYSQ, and VYVGART, among others. Alexion Pharmaceuticals' SOLIRIS is a monoclonal antibody that targets and inhibits complement protein C5, thereby blocking the formation of the terminal complement complex. This action helps reduce complement-driven hemolysis in PNH and thrombotic microangiopathy in aHUS. Although its exact mechanism in gMG and NMOSD is not fully known, it is believed to decrease complement complex accumulation. Between 2017 and 2023, SOLIRIS gained regulatory approvals in Japan, the US, and the EU for treating gMG, including pediatric indications in Japan. ULTOMIRIS (ravulizumab), also from Alexion Pharmaceuticals, is the first long-acting C5 inhibitor, offering rapid, complete, and sustained suppression of complement activity. It binds to C5, preventing its cleavage and subsequent formation of the membrane attack complex (C5b-9). ULTOMIRIS is effective in managing terminal complement-mediated hemolysis in PNH and thrombotic microangiopathy in aHUS. Although the precise mechanism in gMG and NMOSD remains unclear, it is thought to reduce complement deposition at the neuromuscular junction and block aquaporin-4 antibody-mediated complement activation. It received approvals from the US FDA, EMA, and Japan's PMDA in 2022. Get an in-depth assessment on generalized myasthenia gravis medication for adults @ ULTOMIRIS vs SOLIRIS for Myasthenia Gravis UCB Biopharma's RYSTIGGO is a subcutaneously administered, humanized monoclonal antibody that binds with high affinity to the human neonatal Fc receptor (FcRn). It received regulatory approval from the US FDA and Japan's PMDA in 2023, followed by the EC in January 2024. ZILBRYSQ, also developed by UCB Biopharma, is the first once-daily subcutaneous peptide-based inhibitor specifically targeting complement protein C5. It works by blocking C5 cleavage and the formation of the terminal complement complex C5b-9. Although its precise action in gMG remains uncertain, it is thought to limit C5b-9 accumulation at the neuromuscular junction. ZILBRYSQ gained approval from the US FDA, EMA, and PMDA in 2023. VYVGART, from Argenx, is a human IgG1 antibody fragment that targets FcRn, leading to a decrease in circulating IgG autoantibodies. It is the first FcRn blocker to receive regulatory approval. Argenx's VYVGART HYTRULO (also marketed as VYVDURA) combines efgartigimod alfa, an FcRn inhibitor, with hyaluronidase, an endoglycosidase, for treating adults with generalized myasthenia gravis. This formulation was approved by the US FDA and EMA in 2023 and by the PMDA in January 2024. Uncover the mechanism of FcRn inhibitor myasthenia gravis medication @ Myasthenia Gravis MoA On April 30, 2025, the FDA approved Johnson & Johnson's nipocalimab, branded as IMAAVY, as a new therapy for gMG. This approval puts IMAAVY among the list of approved drugs for myasthenia gravis treatment. The approval, which J&J says encompasses the widest eligible patient population with gMG, includes individuals aged 12 and above who test positive for AChR or anti-muscle-specific kinase (MuSK) antibodies. IMAAVY functions by inhibiting the FcRn protein, which plays a role in maintaining circulating IgG antibodies, key drivers in many autoimmune disorders. By blocking FcRn, IMAAVY significantly reduces harmful IgG autoantibodies while preserving the body's overall immune response, according to clinical data. J&J sees broader potential for IMAAVY beyond gMG, believing its mechanism of action could apply across multiple autoimmune conditions due to IgG's involvement in various diseases. The FDA's decision followed results from the ongoing Phase III Vivacity-MG3 trial, which evaluates IMAAVY in combination with standard care versus placebo and standard care in 199 adult gMG patients, including 153 antibody-positive individuals. Additionally, J&J is conducting a Phase II/III pediatric trial called Vibrance, where IMAAVY, combined with standard care, achieved its primary goal by reducing total serum IgG levels by 69% over 24 weeks. J&J acquired IMAAVY through its USD 6.5 billion acquisition of Momenta Pharmaceuticals in 2020, with the FcRn inhibitor myasthenia gravis serving as the centerpiece of that deal. The company is aiming for blockbuster status, forecasting peak annual sales of over USD 5 billion for the myasthenia gravis medication. Dive deep into the myasthenia gravis treatment cost @ Generalized Myasthenia Gravis Drug with Copay Myasthenia gravis pipeline possesses some drugs in mid- and late-stage development to be approved in the near future. The expected launch of myasthenia gravis treatment medications, such as Batoclimab (Immunovant Sciences GmbH), Descartes-08 (Cartesian Therapeutics), and others, are expected to further create a positive impact on the myasthenia gravis disease market. Discover which therapies are expected to grab major myasthenia gravis therapeutics market share @ Market Analysis on Myasthenia Gravis Batoclimab is a fully humanized monoclonal antibody designed to inhibit neonatal Fc receptors by blocking the interaction between FcRn and IgG, thereby promoting the breakdown of autoantibodies. It has received Orphan Drug Designation (ODD) from both the US FDA and the EMA. In March 2025, Immunovant announced topline results from its Phase III trial evaluating batoclimab in patients with myasthenia gravis. Descartes-08 represents the first RNA-engineered CAR T-cell (rCAR-T) therapy developed for autoimmune conditions. This therapy uses cytotoxic T-cells programmed to target and eliminate pathogenic plasma cells that produce autoantibodies. Created from a patient's own blood, Descartes-08 has also received ODD from the US FDA for treating myasthenia gravis. In December 2024, Cartesian Therapeutics shared encouraging updated findings from its Phase IIb study of Descartes-08 in myasthenia gravis. Furthermore, in January 2025, the FDA agreed to the company's Phase III AURORA trial design under a Special Protocol Assessment, with trial initiation planned for the first half of 2025. Curious about what the new myasthenia gravis treatments are in development? Visit Myasthenia Gravis Clinical Trials The anticipated launch of these emerging myasthenia gravis treatments are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the myasthenia gravis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the myasthenia gravis market size in the 7MM is expected to grow from USD 5.2 billion in 2024 at a significant CAGR by 2034. According to DelveInsight's analysis, the myasthenia gravis market growth is anticipated with the introduction of emerging therapies, leading to an expansion in the myasthenia gravis market size throughout the forecast period (2025–2034). This anticipated myasthenia gravis market growth is driven by advancements in treatment options, greater healthcare access, and a rising myasthenia gravis prevalence, which together foster higher demand for innovative and effective therapies. DelveInsight's latest published market report titled Myasthenia Gravis Market Insight, Epidemiology, and Market Forecast – 2034 will help you to discover which myasthenia gravis treatment market leader is going to capture the largest market share. The report provides comprehensive insights into the country-specific myasthenia gravis treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The myasthenia gravis market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM, segmented into: Total Diagnosed Prevalent Cases of Myasthenia Gravis Gender-specific Diagnosed Prevalent Cases of Myasthenia Gravis Age-specific Diagnosed Prevalent Cases of Myasthenia Gravis Diagnosed Prevalent Cases of Myasthenia Gravis by MGFA Classification Diagnosed Prevalent Cases of Generalized Myasthenia Gravis by Antibody Serology The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM myasthenia gravis market. Highlights include: 10-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this myasthenia gravis market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the myasthenia gravis market. Also, stay abreast of the mitigating factors to improve your market position in the myasthenia gravis therapeutic space. Related Reports Myasthenia Gravis Epidemiology Forecast Myasthenia Gravis Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted myasthenia gravis epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Myasthenia Gravis Pipeline Myasthenia Gravis Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key myasthenia gravis companies, including Harbour BioMed (Guangzhou) Co. Ltd., Kyverna Therapeutics, Cabaletta Bio, Takeda, Hoffmann-La Roche, Immunovant Sciences GmbH, Regeneron Pharmaceuticals, Novartis Pharmaceuticals, Janssen Research & Development, LLC, Momenta Pharmaceuticals, Inc., Amgen, Dianthus Therapeutics, Cartesian Therapeutics, COUR Pharmaceutical Development Company, Inc., Alexion Pharmaceuticals, Inc., among others. Generalized Myasthenia Gravis Market Generalized Myasthenia Gravis Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key gMG companies including Alexion Pharmaceuticals, Argenx, UCB Biopharma, Argenx-Halozyme Therapeutics, Horizon Therapeutics, Hoffmann-La Roche, Janssen Research & Development, LLC, Immunovant Sciences GmbH, Bristol Myers Squibb, Biogen Inc., Pfizer Inc., Novartis AG, Sanofi S.A., Roche Holding AG, Johnson & Johnson, Takeda Pharmaceutical Company Limited, AbbVie Inc., Eli Lilly and Company, Merck & Co., Inc., GlaxoSmithKline plc, AstraZeneca plc, Amgen Inc., Boehringer Ingelheim International GmbH, Genentech, Inc., Gilead Sciences, Inc., Celgene Corporation, Vertex Pharmaceuticals Incorporated , among others. Generalized Myasthenia Gravis Pipeline Generalized Myasthenia Gravis Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key gMG companies, including Biocon, Cartesian Therapeutics, UCB, Momenta Pharmaceuticals, HanAll Biopharma, Roche, Alexion, Novartis, Takeda, BioMarin, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . 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同写意年度巨献！！大会特设“细胞药物创新前沿”分会，7月25-26日，邀您相聚金鸡湖畔，与5000人一起为中国医药创新“同写意”！2023年，德国的Georg Schett教授等人总结了2010年1月至2022年12月期间的CAR-T细胞与自身免疫性疾病的文献，发表于《柳叶刀》，主题为“CAR T细胞疗法在自身免疫性疾病中的应用”。随后，包括Schett教授团队在内的研究人员陆续发表了小样本量的临床结果。2025年3月，柳叶刀子刊《Lancet Rheumatology》杂志刊登了来自法国和美国的研究人员针对以上主题的最新综述，其中总结了来自德国和意大利研究团队的临床数据，题为“CAR T-cell therapy in autoimmune diseases: where are we and where are we going”。本期将给大家分享其主要内容。自身免疫性疾病的治疗策略涉及使用免疫抑制药物来控制疾病进展，并减少发作。无法控制的炎症可能会导致器官功能障碍和纤维化，即使在治疗后也可能持续存在。治疗自身免疫性疾病的一个关键挑战是找到合适的治疗平衡，以防止损伤同时避免不良反应，例如感染。目前为止，接受CAR T细胞治疗的患者对多种免疫抑制治疗产生耐药性，并且存在一些器官损伤（例如肺纤维化）。鉴于CAR T细胞治疗的成本和复杂性，对此类患者进行该治疗需谨慎。TONACEA01CD19 CAR T细胞治疗自身免疫性疾病的证据目前，CD19 CAR T细胞应用的证据来自没有对照组的多个病例，随访时间有限。该研究汇总了接受CD19 CAR T细胞治疗的自身免疫性疾病患者包括8名系统性红斑狼疮（SLE）患者、5名系统性硬化症患者以及5名特发性炎症性肌病患者（其中4名为抗合成酶综合征患者，1名为幼年型皮肌炎患者）。所有接受治疗的患者均患有严重且难治性疾病。所有SLE患者均有皮肤受累和增生性肾炎，所有系统性硬化症患者均有间质性肺病（ILD），表现为用力肺活量和肺一氧化碳弥散量降低，4名抗合成酶综合征患者（3名抗Jo-1抗体阳性，1名抗PL-7抗体阳性）均有肌炎和ILD。其他器官受累包括皮疹（2名）和关节炎（1名）。患有血清阴性皮肌炎的患者有肌病、溃疡性皮疹和广泛性钙化。所有患者在接受CAR T细胞治疗前均接受了多种免疫抑制药物治疗。患者在进行CAR T细胞治疗前需停用免疫抑制药物一段时间（洗脱期），以优化T细胞的采集和体外扩增。洗脱期通常为7天至4周，中位数为3周，同时需减少皮质类固醇剂量。在患有严重危及生命疾病的患者中，这一时期尤其具有风险，缩短这一时期可提高安全性。患者接受的CAR T细胞数量范围为每公斤体重1×10⁶至5×10⁶个CAR-T细胞。所有患者均接受了淋巴细胞清除化疗预处理（氟达拉滨和环磷酰胺），但治疗方案在持续时间和剂量上存在差异。2名患者因肾功能受损而接受了50%的剂量减少。系统性自身免疫性疾病患者跟肿瘤患者不一样，可能不需要强烈的CAR T细胞扩增。2024年有一项中国团队的研究使用了CD19和BCMA复合CAR T细胞，并采用了简化的清淋方案（仅使用300毫克每平方米的环磷酰胺，不使用氟达拉滨），结果显示CAR T细胞扩增和临床疗效均达到最佳。因此，是否需要减少清淋值得进一步研究。接受二代CAR T细胞的患者中，CAR T细胞迅速扩增，在大约7至9天达峰。CAR T细胞在接受过利妥昔单抗治疗的患者体内扩增低于未经利妥昔单抗治疗的患者。大部分患者体内的CAR T细胞在输注后28至78天无法检测到，而接受三代CAR T细胞治疗的患者输注后800天依然能被检测到。有1名患者体内CAR T细胞在输注后11个月能被检测到，但这并未产生临床获益。除1名患者外，所有患者在接受CD19 CAR T细胞治疗后，CD19+ B细胞在数天内迅速从外周血中消失。B细胞在3个月后重新出现在外周血中，且免疫球蛋白水平逐渐恢复。与未接受过利妥昔单抗治疗的患者相比，之前接受过利妥昔单抗治疗的患者B细胞重建时间更长。所有接受CD19 CAR T细胞治疗的SLE患者，其血清自身抗体滴度显著且迅速下降，尤其是抗双链DNA、抗单链DNA、抗核小体和抗Smith蛋白抗体。对重建的B细胞亚群分析显示，其呈现幼稚表型，CD27+记忆B细胞显著减少，这表明体液免疫库重置。在SLE患者中，致病性B细胞，如CD27+CD38+浆母细胞和与SLE相关的激活的CD11c+记忆B细胞，在B细胞重建后未被检测到。  在接受CAR T细胞治疗的18名自身免疫性疾病患者中，没有出现高级别的CRS或ICANS。在短期安全性方面，18名患者中有14名（78%）出现了CRS，其中13名为1级，有6名（33%）患者接受了托珠单抗治疗。患者均未出现长期或双相的骨髓抑制。在长期安全性方面，轻度上呼吸道感染多见，发生在治疗后的3个月至超过12个月之间。18名患者中有5名（28%）出现低丙种球蛋白血症。没有报告癌症病例。CD19 CAR T细胞治疗SLE、系统性硬化症以及特发性炎症性肌病的疗效和临床反应持久性总结如下：• 8名SLE患者在6个月时均达到缓解标准；最长达29个月的长期随访显示，所有患者均保持临床、生物学和免疫学缓解状态；1名患者在治疗4个月时出现孤立性蛋白尿反弹，但没有临床和组织学复发的迹象。• 3名特发性炎症性肌病患者在3个月内迅速改善，在长达12个月内疗效得以维持；1名患者在治疗后7天出现临床和生物学疾病活动恶化；在1名血清阴性幼年型皮肌炎患者中，所有疾病表现（包括肌力和皮肤症状，如皮肤溃疡和钙化）在治疗后4周开始改善，且在停用免疫抑制药物和泼尼松后，这种改善持续长达8个月。• 6名系统性硬化症患者在3个月和6个月时，疾病评分有所下降；在ILD患者中，随访显示肺容积稳定或略有改善。• 截至2024年11月，CD19 CAR T细胞治疗的最长随访数据显示，SLE为29个月，特发性炎症性肌病为18个月，系统性硬化症为18个月，所有患者均维持缓解或低疾病活动度。然而，有1名特发性炎症性肌病患者出现复发，肌酸磷酸激酶重新升高；该患者随后被给予相同批次的CD19 CAR T细胞再次治疗，但未能实现扩增和临床效果；随后，该患者接受了达雷妥尤单抗（抗CD38）治疗，取得了良好的生物学和临床效果。这一复发提示CD19阴性B细胞（包括自身反应性浆细胞）可能参与疾病复发。CAR T细胞治疗后，联合治疗显著减少。有15名患者在最后一次随访时（中位数为15个月）成功停用了皮质类固醇和免疫抑制剂。TONACEA02自身免疫性疾病的其他靶点更分化的B细胞，如长期记忆B细胞和浆细胞，为分泌抗体的细胞，在自身免疫性疾病中起关键作用，这提示了靶向那些细胞的必要性。▲图1: B细胞及其他自身免疫性疾病相关细胞的抗原靶点。BAFF = B细胞激活因子（B-cell activating factor）。BCMA = B细胞成熟抗原。FAP = 成纤维细胞激活蛋白。（来源：Scherlinger M，Lancet Rheumatol，2025；Figure 2）靶向BCMA已在少数自身免疫性疾病中进行了测试，如视神经脊髓炎、抗SRP坏死性肌病和与抗CD19联合用于SLE。有研究显示，BCMA或针对BCMA和CD19双靶点的CAR T细胞可迅速降低自身抗体，但几乎所有患者都出现了低丙种球蛋白血症。大多数患者的IgG浓度在6-12个月内恢复正常或接近正常。值得注意的是，在抗SRP坏死性肌病患者中使用BCMA CAR T细胞治疗可清除外周循环B细胞，尽管所有循环B细胞均不表达BCMA。这一现象可能归因于清淋化疗，但类似的B细胞的清除也见于CD3和BCMA双特异性抗体治疗，这些抗体治疗不需要清淋化疗，表明存在BCMA介导的效应。其他正在开发中的靶点中，CD138因其在浆细胞上有较高特异性而被关注（图2）。CD138 CAR T细胞可在体外和异种移植小鼠模型中清除多发性骨髓瘤细胞。CD138和CD38双靶 CAR T细胞值得关注，因为抗CD38治疗已被证明在各种自身免疫性疾病中有效，且CD38在自身免疫患者外周和组织浆细胞中有表达。在几种系统性自身免疫性疾病中，组织炎症可能进展为组织纤维化。纤维化疾病对健康、经济和社会造成了重大负担，因为其发病率增加、发病率和死亡率高以及治疗选择有限。靶向激活的成纤维细胞的FAP的CAR T细胞在治疗纤维化疾病方面引起了人们相当大的兴趣。FAP表达在免疫抑制、促血管生成和细胞内信号传导调节中发挥关键作用。通过清除表达FAP的成纤维细胞（图2），FAP CAR T细胞可直接减少纤维化负担，逆转或阻止组织中纤维化的进展。在心脏纤维化的动物模型研究中，FAP CAR T细胞减少了组织纤维化。FAP CAR T细胞在多种纤维化疾病（包括肝脏、肺部、心脏和肾脏的器官纤维化以及系统性硬化症）中具有治疗潜力，通过中断慢性炎症转变为纤维化的反馈循环，并通过消除导致细胞外基质过度产生的细胞来减少纤维化。TONACEA03靶向自身反应性、抗原特异性细胞直接靶向自身反应性（autoreactive）细胞可减少CAR T细胞引起的免疫抑制，并提高安全性。有研究人员构建了一个与自身抗原融合的T细胞受体，来开发嵌合自身抗原T细胞受体（chimeric autoantigen T cell receptor，CATCR）T细胞（图2），旨在仅清除自身免疫B细胞，而不清除其他B细胞。要使这一策略适用于自身免疫性疾病，必须满足两个条件：1. 必须识别出一种或多种自身抗原；2. 表达自身抗原的细胞群必须在病理中发挥作用，而不仅仅是自身免疫的间接表现。重症肌无力有抗乙酰胆碱受体和抗肌肉特异性受体酪氨酸激酶（MuSK）自身抗体。针对重症肌无力，有人构建了表达MuSK嵌合自身抗体受体的T细胞，该受体具有CD137-CD3ζ信号传导结构域（MuSK-CATCR），以精确靶向表达抗MuSK自身抗体的B细胞。在小鼠模型中，MuSK-CATCR降低了抗MuSK IgG，而没有降低B细胞或总IgG浓度，表明具有MuSK特异性的B细胞清除能力。针对天疱疮的抗桥粒蛋白3（Dsg3）自身抗体的CATCR T细胞（Dsg3-CATCR T细胞）也产生了类似的效果。针对抗磷脂综合征，有研究在测试靶向β2GP1自身抗原使用嵌合自身抗原受体（chimeric auto-antigen receptor，CAAR）T细胞的可能性（图2）。在表达抗B2GPI B细胞受体的Ramos B细胞系中，这种CAAR T细胞显示出对自身反应性B细胞的特异性靶向。针对狼疮肾炎，Sole等人测试了与dsDNA具有交叉反应的不同抗原靶点，包括α-actinin、组蛋白-1、肝素硫酸盐或C1q，其中抗肝素硫酸盐和抗C1q策略可能可以靶向抗dsDNA B细胞。这种策略的潜在治疗价值在肾脏类器官模型中得到了评估。▲图2: 抗原特异性受体的CAAR T细胞和CATCR T细胞。（来源：Scherlinger M，Lancet Rheumatol，2025；Figure 1）TONACEA04恢复调节性T细胞功能调节性T细胞（Treg）是表达FoxP3的CD4+ T细胞亚群，通过多种机制调节免疫反应。尽管Treg细胞的激活是抗原依赖的，但激活后，其免疫抑制机制是抗原非依赖的。大多数系统性自身免疫性疾病存在Treg细胞数量或功能缺陷，因此旨在恢复功能失调的Treg细胞的策略是研究的重点。在遇到靶抗原时，CAR Treg细胞会扩增并诱导局部免疫抑制。多个自身免疫性疾病的临床前模型已经验证了CAR Treg细胞的潜力。在移植领域已有CAR Treg细胞进入临床阶段。另一种有前景的策略是使用人工免疫受体（artificial immune receptor，AIR）-Treg细胞（图3）靶向炎症本身，而不是特定自身抗原。与识别抗原的单链可变片段不同，构建物中包含细胞因子受体片段，如TNF受体2或淋巴毒素β受体，这可使Treg细胞在炎症部位激活。这种策略允许AIR Treg细胞的特异性扩增到所有炎症组织。AIR Treg细胞在移植物抗宿主病模型中改善了组织炎症和总体生存率。在未来，确保CAR激活后保持Treg细胞样表型是必要的。▲图3: CAR Treg细胞和AIR Treg细胞。（来源：Scherlinger M，Lancet Rheumatol，2025；Figure 1）TONACEA05改善CAR T细胞疗法和构建CAR的策略由于自身免疫疾病患者接受CD19 CAR T细胞治疗的数量较少，且总体临床反应良好，因此耐药机制尚不清楚。然而，过去10年在肿瘤学中获得的一些知识可以类推到自身免疫性疾病中。CAR T细胞在自身免疫性疾病中的迁移依赖于靶细胞的位置。T细胞进入淋巴结和骨髓将比进入受损器官更容易。由于CD19 CAR T细胞可使正常和自身反应性B细胞的快速消失，表明工程化T细胞能够到达其靶标。然而，T细胞的迁移可能在纤维化器官中更为困难，这可以利用前述的抗纤维化策略。炎症和纤维化微环境也对CAR T细胞的其他功能产生负面影响。为了使CAR T细胞对这些抑制因素不敏感，研究人员已在测试许多策略。例如，在前列腺癌中，PSMA CAR T细胞表达一个显性负TGF-β受体，已在一些患者中显示出临床疗效。在血液恶性肿瘤中，CD19 CAR T细胞的强烈选择压力可使肿瘤细胞发生CD19基因的突变或缺失，导致CD19基因表达沉默。克服CD19阴性逃逸的策略包括两种CAR T细胞产品联用，分别靶向CD19和另一种B细胞抗原，如CD22或BCMA。在接受自身免疫性疾病治疗的患者中，CAR T细胞的持续存在可能与长期安全性问题有关，例如低丙种球蛋白血症或继发性肿瘤。此外，由于CD19 CAR T细胞治疗的临床效应被认为是通过B细胞库重置介导的，因此长期的CAR T细胞持续存在可能并不理想。使用NK细胞或γδ T 细胞可能满足短期持续存在的需求，且可制备成现货型治疗产品（图4）。NK细胞没有(经典的)免疫记忆，也不会长期持续存在。此外，NK细胞不表达HLA系统，这使得使用异体CAR NK细胞成为可能，这可缩短洗脱期（图4）。此外，CAR NK细胞疗法可能与较低的CRS和ICANS风险相关。已有研究人员开发了靶向CD19、CD138和BCMA的CAR NK细胞，并进入临床阶段。使用基因编辑技术（例如，CRISPR/Cas9）去除人供体T细胞上的HLA分子、T细胞受体和抑制受体（例如PD1）的表达，并将CAR转导到这些细胞上，已在1例坏死性肌病患者和2例系统性硬化症患者中显示出良好的效果（图4）。仅诱导CAR瞬时表达的策略（例如mRNA技术）也正在被开发（图4）。有研究采用抗CD5脂质纳米颗粒，在体内递送FAP CAR到T细胞。在血管紧张素-II诱导的心力衰竭的临床前模型中，这种策略显著减少了心肌纤维化。 ▲图4: CAR在人体内应用的现行和未来策略。（来源：Scherlinger M，Lancet Rheumatol，2025；Figure 3）TONACEA06局限性和展望01物流和成本挑战CAR T细胞疗法在物流方面要求很高，从血细胞分离到CAR T细胞输注，涉及不同专业知识的人员，以及一个规范认证的平台来进行T细胞转导、扩增和治疗前检测。这一问题以及当前疗法本身的成本是CAR疗法可及性有限的主要障碍，特别是对于低收入人群。02治疗时间框架从确定治疗到CAR T细胞输注的时间跨度为2-3周到超过6周，这包括免疫抑制药物洗脱期、血细胞分离、CAR T细胞生产、质量检查以及CAR T细胞输注前的清淋（图5）。如何快速治疗患有严重或难治性疾病的患者的问题有待解决。03靶点选择尽管CD19是自身免疫性疾病中第一个使用的靶点，但存在其他免疫靶点（例如BCMA和CD38）和非免疫靶点（例如FAP），并且在未来可能会出现更多。需要评估每个靶点的疗效和安全性，并且最适合每个患者的靶点。04长期安全性问题鉴于基因修饰，包括对未来怀孕的风险以及继发性恶性肿瘤的风险，CAR T细胞疗法的长期安全性问题备受重视(图5)。05可持续性和替代疗法如果其他更便宜且现成可用的疗法能达到相同的疗效，那么可能需要考虑CAR T细胞疗法的可持续性。其中，双特异性T细胞或NK细胞T细胞接合剂（T-cell engager）显示出极大的潜力。▲图5: 与CAR T细胞疗法相关的安全性问题。IEC-HS可能在第4天至第32天之间出现。ICU=重症监护病房。IEC-HS=免疫效应细胞相关噬血细胞性淋巴组织细胞增多症样综合征。（来源：Scherlinger M，Lancet Rheumatol，2025；Figure 4）参考文献：（上下滑动查看更多）[1] Schett G, Mackensen A, Mougiakakos D. 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Third-generation CD19.CAR-T cell-containing combination therapy in Scl70+ systemic sclerosis. Ann Rheum Dis. 2024 Mar 12;83(4):543-546. PMID: 38135464; PMCID: PMC10958299.[7] Nicolai R, Merli P, Moran Alvarez P, et al. Autologous CD19-Targeting CAR T Cells in a Patient With Refractory Juvenile Dermatomyositis. Arthritis Rheumatol. 2024 Oct;76(10):1560-1565. PMID: 38924652