Pilot Study of Emapalumab With Post-Transplant Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis for Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

This phase I trial tests the safety, side effects and effectiveness of emapalumab with post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil in preventing graft-versus-host disease (GVHD) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after reduced-intensity donor (allogeneic) hematopoietic cell transplant (HCT). Giving chemotherapy, such as fludarabine, melphalan, or busulfan, before a donor [peripheral blood stem cell] transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When healthy stem cells for a donor are infused into a patient (allogeneic HCT), they may help the patient's bone marrow make more healthy cells and platelets. Allogeneic HCT is an established treatment, however, GVHD continues to be a major problem of allogeneic HCT that can complicate therapy. GVHD is a disease caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Emapalumab binds to an immune system protein called interferon gamma. This may help lower the body's immune response and reduce inflammation. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill cancer cells. It may also lower the body's immune response. Tacrolimus is a drug used to help reduce the risk of rejection by the body of organ and bone marrow transplants. Mycophenolate mofetil is a drug used to prevent GVHD after organ transplants. It is also being studied in the prevention of GVHD after stem cell transplants for cancer, and in the treatment of some autoimmune disorders. Mycophenolate mofetil is a type of immunosuppressive agent. Giving emapalumab with post-transplant cyclophosphamide, tacrolimus and mycophenolate mofetil may be safe, tolerable and/or effective in preventing GVHD in patients with AML or MDS after a reduced-intensity allogeneic HCT.

开始日期2026-05-25

申办/合作机构

City of Hope National Medical Center

[+1]

NCT07244419

/ Recruiting早期临床1期IIT

Emapalumab for the Prevention of Graft Rejection in Hematopoietic Stem Cell Transplant (HSCT) Recipients

The investigators hypothesize that graft rejection after hematopoietic stem cell transplant (HSCT) is primarily driven by interferon gamma, and prophylactic interferon gamma inhibition in high-risk patients will prevent graft rejection. Additionally, knowledge of emapalumab PK/PD and in vitro mechanistic effects of emapalumab in this novel setting will guide optimization of dosing regimens and treatment approaches in future studies.

开始日期2026-01-07

申办/合作机构

Children's Hospital & Medical Center

[+1]

NCT07202598

/ Recruiting临床2期IIT

A Phase 2 Randomized Stepped Wedge Study of Emapalumab in APECED Enteritis

Background:
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as Autoimmune polyendocrine syndrome type-1 (APS-1), is a disease that causes the immune system to attack parts of a person s body. In some people, APECED attacks the small intestine; this causes an illness called enteritis.
Objective:
To test a drug (emapalumab) in people with enteritis caused by APECED.
Eligibility:
People aged 2 to 75 years with APECED and enteritis. They must also be enrolled in protocol 11-I-0187.
Design:
Participants will have 10-13 study visits in an 18-month period.
Participants will be screened. They will have a physical exam with blood tests. These tests will be repeated at every study visit. They will have a test of their heart function. This will be at screening and prior to drug administration.
Other tests are optional: Participants may have imaging exams and a test of lung function. They may have an endoscopy, which is an exam of their digestive tract. Participants may provide samples of urine, stool, nail clippings, saliva, vaginal fluid, or skin. Photos may be taken of their skin or scalp. These tests may be repeated at some visits.
Emapalumab is given through a tube attached to a needle inserted into a vein. All participants will receive 7 doses: 2 on their first study visit; then 1 each at 30-day intervals. Some participants will have an observation period before they begin taking the drug; in those situations, they will either be seen in person or via video visit every 2 months before starting emapalumab to see how their symptoms change over time.
Participants will have a follow-up visit 1 month after their last dose. Then they will have 2 telehealth visits at 30-day intervals. They will have a final clinic visit 1 year after their first dose.
...

开始日期2025-11-12

申办/合作机构

National Institute of Allergy & Infectious Diseases

100 项与依马利尤单抗相关的临床结果

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100 项与依马利尤单抗相关的转化医学

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100 项与依马利尤单抗相关的专利（医药）

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项与依马利尤单抗相关的文献（医药）

2026-01-01·HEMATOLOGICAL ONCOLOGY

Managing Treatment‐Emergent Immune Effector Cell‐Associated Hemophagocytic Lymphohistiocytosis‐Like Syndrome Following CAR‐T Cell Therapy: A Case‐Based Review of the use of Emapalumab

Review

作者: Di Rocco, Alice ; Torelli, Giovanni Fernando ; Piazzolla, Mario ; Donzelli, Livia ; Zullino, Veronica ; Ruberto, Franco ; De Propris, Maria Stefania ; Martelli, Maurizio

ABSTRACT:

Chimeric antigen receptor T (CAR‐T) cell therapies have revolutionized the treatment of hematological malignancies, achieving high response rates in patients with relapsed or refractory disease. Despite these benefits, CAR‐T cell therapies are associated with unique toxicities, including cytokine release syndrome (CRS), immune effector cell‐associated neurotoxicity syndrome (ICANS), immune cell‐associated hematotoxicity (ICAHT), and immune effector cell‐associated hemophagocytic lymphohistiocytosis‐like syndrome (IEC‐HS), which is characterized by a rare and life‐threatening hyperinflammatory response. This paper presents a case of a 56‐year‐old woman with relapsed mantle cell lymphoma (MCL) treated with the CAR‐T cell therapy, brexucabtagene autoleucel, who had subsequently developed CRS and later IEC‐HS. Initial management included tocilizumab, corticosteroids, and anakinra, followed by the compassionate use of emapalumab, an interferon‐γ blocker. To provide broader context, we conducted a literature review of CAR‐T cell‐related toxicities, focusing on IEC‐HS and its management with emapalumab. Clinical and laboratory manifestations, such as elevated ferritin levels, cytopenias, and organ dysfunction, underpin the diagnostic criteria for IEC‐HS. Vigilant monitoring and tailored therapeutic approaches are required to effectively manage toxicities associated with CAR‐T cell therapy, to maximize its benefits and minimize adverse effects. In more severe IEC‐HS cases, emapalumab may be used as an effective targeted therapy.

2025-12-31·ANNALS OF MEDICINE

Efficacy of emapalumab in treating 3 pediatric patients with epstein–barr virus-associated hemophagocytic lymphohistiocytosis complicated by multiple organ dysfunction

Article

作者: Ma, Honghao ; Wang, Quan ; Liu, Jun ; Qian, Suyun ; Liu, Gang

BACKGROUND AND OBJECTIVE:

Epstein-Barr virus-associated hemophagocytic lympho-histiocytosis (EBV-HLH) is common among HLH in paediatric patients, severe cases are often complicated by multiple organ dysfunction syndrome (MODS), leading to poor prognosis and high mortality rate. Emapalumab, an interferon (IFN)-γ inhibitor, can effectively improve patient prognosis without MODS, but it remains unclear whether patients with MODS can achieve clinical benefits. In this study, we aim to evaluate the efficacy and safety of emapalumab in treating EBV-HLH with MODS.

METHODS:

The paediatric cases admitted to the paediatric intensive care unit were prospectively included, with worsening labs and IFN-γ > 500 pg/mL after standard care, and were given intravenous infusions of emapalumab at a dose of 1-2 mg/kg. Outcomes measured included body temperature, lab results, in-hospital mortality, and stem cell transplant rates.

RESULTS:

Three paediatric cases were included, and treatment was uninterrupted. Among these, Case 2 exhibited refractory EBV-HLH. After conventional therapy, the laboratory parameters, hyperthermia and pSOFA score remained unimproved withthe blood IFN-γ > 500 pg/mL. Emapalumab infusion was administered, with significant improvement within one week. Case 2 later developed a cytomegalovirus infection, leading to treatment discontinuation despite stable IFN-γ level. Cases 1 and 3 remained stable without additional treatments during a one-year follow-up.

CONCLUSION:

The use of emapalumab to treat paediatric patients with EBV-HLH complicated by MODS can significantly improve body temperature and HLH-related laboratory parameters, but the overall clinical benefit for refractory cases remains unclear. During treatment, it is essential to keep vigilance against concurrent infections, and monitoring for potential latent pathogens is also warranted.

2025-12-02·Zhonghua er ke za zhi = Chinese journal of pediatrics

[Advance and perspectives of emapalumab in hemophagocytic lymphohistiocytosis treatment].

Review

作者: Xu, X J ; Qian, Y Y

项与依马利尤单抗相关的新闻（医药）

2026-01-24

·三优生物医药

三优十周年｜从库到药：盘点诺奖技术“噬菌体展示”孕育的抗体药物

作者：周予西美工：何国红罗真真排版：马超 ▶ 01 引言噬菌体展示技术自1985年问世以来，彻底改变了抗体药物的研发路径。2018年诺贝尔化学奖的颁发，让这项“让噬菌体为人类打工”的技术从实验室走向聚光灯下。如今，这项技术已催生出一个庞大的治疗性抗体家族，它们被用于治疗从类风湿关节炎到癌症等多种疾病。从第一个基于该技术开发的“药王”修美乐，到最新获批的国产创新药赛立奇单抗，噬菌体展示技术正在重塑全球抗体药物研发格局。 ▶ 02 抗体文库：多样性的源泉与技术的演进噬菌体展示技术的强大能力，源于其使用的核心工具——抗体文库。根据序列来源与构建方式，主要分为四种类型，以应对不同研发需求。 ◑ 天然库由未经免疫的健康人B细胞构建，旨在模拟人体天然的抗体多样性，其优势是“广谱性”，可针对几乎所有抗原进行筛选，但初始抗体亲和力通常较低。 ◐ 免疫库采用经过特定抗原免疫的人或动物B细胞构建，优势在于“精准性”，文库富含靶向该抗原的序列，能高效筛选出高亲和力抗体，但应用范围仅限于其免疫的抗原。 ◑ 半合成库通过基因工程，将人工合成的随机序列（主要针对关键互补决定区CDR）与天然的抗体框架区组合而成，在天然库基础上引入了可控的多样性。 ◐ 合成库的序列则完全通过人工设计与化学合成，是工程化程度最高的文库，可从头优化骨架、系统引入多样性，并能规避天然序列的专利或免疫原性问题。 ▲ 图 1 三优生物噬菌体展示库概览三优生物已构建了国际领先的“智能超万亿分子发现平台”，噬菌体抗体库种类多样，可以覆盖几乎所有的抗体产生需求。同时，三优生物的AI-STAL噬菌体抗体库在行业内也具备显著优势。 ▲ 图2 三优生物与其他行业内企业抗体噬菌体展示库对比 ▶ 03 药物盘点与典型案例噬菌体展示技术自实现产业化以来，已催生出一个覆盖多种疾病领域的治疗性抗体家族，噬菌体来源的抗体约占比20%，适应症涵盖了从自身免疫病到癌症的广泛适应症，并不断向双特异性抗体等创新形式拓展。 01 肿瘤治疗领域肿瘤治疗长期面临精准性不足、耐药性频发等难题，而噬菌体展示技术凭借其强大的靶向筛选能力与多样化抗体构建优势，在该领域大放异彩，催生了从裸抗体、免疫检查点抑制剂到抗体偶联药物（ADC）、双特异性抗体的多种创新疗法。这些药物不仅能精准识别肿瘤细胞特异性抗原，阻断关键增殖或血管生成通路，还能通过激活机体自身免疫反应或直接递送毒性分子杀伤癌细胞，为不同阶段、不同类型的肿瘤患者提供了多元化治疗选择。雷莫芦单抗（Ramucirumab）：靶向血管内皮生长因子受体2 (VEGFR2) 的全人源单克隆抗体，通过噬菌体展示技术发现。它精确阻断VEGF与受体的结合，抑制肿瘤血管生成。2014年首次获批用于晚期胃癌，后适应症扩展至非小细胞肺癌、结直肠癌、肝细胞癌等多个癌种，成为抗血管生成治疗的中坚力量。纳武利尤单抗（Necitumumab）：全人源IgG1-κ单克隆抗体，选择性结合表皮生长因子受体（EGFR），阻断配体结合及下游信号传导，抑制癌细胞增殖、血管生成等关键过程。2015年获批与吉西他滨、顺铂联合治疗转移性鳞状非小细胞肺癌，为EGFR过表达的癌症患者提供了新的治疗选择。阿替利珠单抗（Atezolizumab）：人源化IgG1-κ免疫检查点抑制剂，靶向PD-L1，阻断其与PD-1结合，恢复肿瘤特异性T细胞免疫力。2016年起陆续获批尿路上皮癌、非小细胞肺癌、三阴性乳腺癌等多个适应症，是癌症免疫治疗领域的重要药物，目前仍有多项临床研究在推进。阿维鲁单抗（Avelumab）：全人源IgG1-λ免疫检查点抑制剂，靶向PD-L1，同时可能通过抗体依赖的细胞毒性（ADCC）发挥作用。2017年获批转移性默克尔细胞癌，后扩展至泌尿系结石癌、肾细胞癌等适应症，为晚期肿瘤患者提供了多元化治疗方案。莫塞妥莫单抗（Moxetumomab pasudotox-tdfk）：重组免疫毒素，由鼠源scFv与截短的假单胞菌外毒素融合而成，靶向CD22抗原，用于治疗复发/难治性毛细胞白血病。2018年获批，是噬菌体展示技术优化抗体亲和力的典型案例，为罕见白血病患者提供了新的治疗选择。 02 自身免疫与炎症性疾病自身免疫与炎症性疾病常伴随免疫系统紊乱，传统治疗药物往往存在疗效有限、副作用明显等问题，而这是噬菌体展示技术最早取得辉煌战绩的领域。该技术通过筛选全人源抗体，从源头降低免疫原性风险，诞生了现代医药史上的“药王”，并推动了一系列精准靶向药物的研发，彻底改变了自身免疫病的治疗格局，让无数患者摆脱了长期依赖激素、疗效不佳的困境。阿达木单抗（Adalimumab）：首个通过噬菌体展示技术上市的全人源抗体药物，2002年获批用于类风湿关节炎。靶向肿瘤坏死因子-α（TNF-α），无需后续人源化改造，疗效与安全性俱佳。上市后成为治疗类风湿关节炎、强直性脊柱炎、银屑病等多种自身免疫病的金标准，曾连续十余年蝉联全球药品销售额榜首，2023年全球销售额仍高达约144亿美元，充分验证了该技术的巨大商业价值。贝利尤单抗（Belimumab）：2011年获批，是首个专门用于治疗系统性红斑狼疮的生物制剂。靶向B细胞刺激因子（BLyS），通过抑制异常活跃的B细胞控制病情，证明了噬菌体展示技术能够攻克复杂、难治的自身免疫病靶点。古塞奇尤单抗（Guselkumab）：全人源IgG1-λ单克隆抗体，靶向IL-23的p19亚基，阻断IL-23/Th17通路，抑制炎症反应。2017年获批治疗中重度斑块状银屑病，后扩展至银屑病关节炎等适应症，为自身免疫性皮肤病和关节病提供了精准治疗方案。依奇珠单抗（Ixekizumab）：人源化IgG4-κ单克隆抗体，靶向IL-17A，抑制炎症因子介导的病理反应。2016年起陆续获批银屑病、银屑病关节炎、强直性脊柱炎等适应症，是自身免疫性疾病领域的重要药物，尤其在银屑病治疗中疗效显著。赛立奇单抗（Serplulimab）：2024年获批，国内首个通过噬菌体展示技术自主研发并上市的全人源抗IL-17A单克隆抗体，用于治疗中重度斑块状银屑病和强直性脊柱炎。从递交上市申请到获批仅用时约17个月，体现了国内在该技术平台上全链条能力的成熟，打破了外资垄断局面。 03 感染性疾病面对突发传染病、耐药菌感染等公共卫生挑战，传统疫苗研发周期长、抗生素滥用导致耐药性等问题日益突出，而抗体作为“被动免疫”疗法的潜力，通过噬菌体展示技术得以充分实现。该技术能快速筛选出高亲和力中和抗体，无需依赖机体主动免疫，可直接用于感染预防或治疗，尤其适用于免疫功能低下人群、突发传染病应急响应等场景，为感染性疾病防控提供了全新的高效解决方案。瑞西巴库单抗（Raxibacumab）：全人源IgG1-λ单克隆抗体，靶向炭疽芽孢杆菌的保护性抗原（PA），中和致命毒素。2012年获批用于吸入性炭疽的预防和治疗，是应对生物恐怖主义的重要药物，彰显了噬菌体展示技术在抗感染领域的应用价值。 04 眼科疾病眼科疾病尤其是眼底病变，因发病部位特殊、药物穿透难度大，长期缺乏有效治疗手段，许多患者面临失明风险。而噬菌体展示技术催生的抗体药物在眼科领域取得了重要突破，通过优化抗体分子大小（如Fab片段），实现了对眼底病变部位的高效穿透与精准靶向，同时兼顾安全性，为湿性年龄相关性黄斑变性、糖尿病黄斑水肿等致盲性眼病提供了有效治疗手段，显著改善了患者的视力预后。雷珠单抗（Ranibizumab）：Fab抗体片段，靶向VEGF-A，抑制眼底新生血管生成。2006年获批治疗湿性年龄相关性黄斑变性，后扩展至糖尿病黄斑水肿、视网膜静脉阻塞等适应症，是眼科抗VEGF治疗的标杆药物，极大改善了患者视力预后。 05 血液系统疾病及其他除了常见疾病领域，噬菌体展示技术的应用持续向更多小众、难治性疾病领域拓展。对于罕见病、血液系统疾病等“缺医少药”的领域，该技术凭借灵活的抗体格式设计（如纳米抗体）、高效的靶点筛选能力，成功突破传统研发瓶颈，为这些疾病提供了创新解决方案，让小众患者群体也能获得针对性治疗，填补了临床治疗空白。卡普拉珠单抗（Caplacizumab）：人源化双价单可变域抗体（VHH），靶向血管性血友病因子（vWF）的A1结构域，用于治疗获得性血栓性血小板减少性紫癜。2018年获批，是首个纳米抗体类药物，体现了噬菌体展示技术在开发新型抗体格式中的灵活性。依玛珠单抗（Emapalumab）：全人源IgG1-λ单克隆抗体，靶向IFNγ，抑制其下游信号传导，用于治疗难治性噬血细胞性淋巴组织细胞增生症。2018年获批，为罕见免疫失调疾病提供了针对性治疗方案，目前还在探索用于COVID-19等疾病的治疗。 ▶ 04 技术创新与未来趋势噬菌体展示技术正通过与前沿科技的融合持续进化。高通量自动化平台与人工智能的深度结合正在重塑抗体发现流程。自动化系统将筛选周期大幅缩短，而人工智能则通过分析海量数据实现了从“试错筛选”到“理性设计”的范式转变，能够预测性能甚至从头设计新序列，为攻克传统难题提供了全新路径。该技术的灵活性使其成为开发双特异性抗体、抗体偶联药物等复杂疗法不可或缺的核心工具。它能有效解决多重蛋白组装中的工程挑战，加速下一代精准药物的诞生。与此同时，技术的应用疆域也在不断拓展。超越肿瘤与自身免疫病等传统领域，研究人员正积极探索其在抗病毒、神经退行性疾病乃至更前沿方向的新治疗可能性。通过与多种创新技术的协同，这一经典平台持续焕发新的活力，有望驱动未来出现更多突破性的治疗方案。 Sanyou 10th Anniversary: From Library to Drug- A Review of Therapeutic Antibodies Derived Phage Display Technology ▶ 01 Introduction Since its advent in 1985, phage display technology has revolutionized the research and development (R&D) landscape of antibody drugs. The awarding of the 2018 Nobel Prize in Chemistry brought this "technology that makes phages work for humans" from the laboratory into the spotlight. Today, this technology has spawned a large family of therapeutic antibodies used to treat a wide range of diseases, from rheumatoid arthritis to cancer. From Humira, the first "blockbuster drug" developed based on this technology, to Serplulimab, the latest approved domestic innovative drug, phage display technology is reshaping the global landscape of antibody drug R&D. ▶ 02 Antibody Libraries: The Source of Diversity and Technological Evolution The powerful capability of phage display technology stems from its core tool-the antibody library. Based on sequence sources and construction methods, it is mainly divided into four types to meet different R&D needs. Naive library: Constructed from B cells of non-immunized healthy humans, it aims to simulate the natural antibody diversity of the human body. Its advantage lies in "broad spectrum", as it can screen against almost all antigens, but the initial antibody affinity is usually low. Immune library: Built using B cells from humans or animals immunized with specific antigens. Its strength is "precision"-the library is enriched with sequences targeting the antigen, enabling efficient screening of high-affinity antibodies, but its application scope is limited to the immunized antigen. Semi-synthetic library: Formed by combining artificially synthesized random sequences (mainly targeting the key complementarity-determining regions, CDRs) with natural antibody framework regions through genetic engineering, introducing controllable diversity on the basis of naive libraries. Synthetic library: Sequences are completely designed and chemically synthesized artificially, making it the most engineered library. It can optimize the scaffold from scratch, systematically introduce diversity, and avoid patent or immunogenicity issues associated with natural sequences. ▲ Fig.1 Overview of the Sanyou Bio Phage Display Library Sanyou Bio has built an internationally leading "Intelligent Trillion-Level Molecule Discovery Platform", offering a diverse range of phage antibody libraries that can cover almost all antibody generation needs. Meanwhile, Sanyou Bio's AI-STAL phage antibody library holds significant advantages in the industry. ▲ Fig.2 Comparison of Antibody Phage Display Libraries Between Sanyou Bio and Enterprises in Other Industries ▶ 03 Drug Inventory and Typical Cases Since the industrialization of phage display technology, it has nurtured a family of therapeutic antibodies covering multiple disease areas. Antibodies derived from phages account for approximately 20%, with indications ranging from autoimmune diseases to cancer, and continue to expand into innovative forms such as bispecific antibodies. 01 Tumor Therapy Tumor therapy has long faced challenges such as insufficient precision and frequent drug resistance. Phage display technology, with its powerful targeted screening capabilities and diverse antibody construction advantages, has shone brightly in this field, spawning various innovative therapies from naked antibodies and immune checkpoint inhibitors to antibody-drug conjugates (ADCs) and bispecific antibodies. These drugs can not only accurately recognize tumor-specific antigens, block key proliferation or angiogenesis pathways, but also kill cancer cells by activating the body's own immune response or directly delivering toxic molecules, providing diversified treatment options for tumor patients at different stages and with different types. Ramucirumab: A fully human monoclonal antibody targeting vascular endothelial growth factor receptor 2 (VEGFR2), discovered through phage display technology. It precisely blocks the binding of VEGF to its receptor and inhibits tumor angiogenesis. First approved for advanced gastric cancer in 2014, its indications have since expanded to non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma and other cancer types, becoming a backbone of anti-angiogenic therapy. Necitumumab: A fully human IgG1-κ monoclonal antibody that selectively binds to epidermal growth factor receptor (EGFR), blocking ligand binding and downstream signaling, thereby inhibiting key processes such as cancer cell proliferation and angiogenesis. Approved in 2015 for the treatment of metastatic squamous non-small cell lung cancer in combination with gemcitabine and cisplatin, it provides a new treatment option for cancer patients with EGFR overexpression Atezolizumab: A humanized IgG1-κ immune checkpoint inhibitor targeting PD-L1, which blocks its binding to PD-1 and restores tumor-specific T cell immunity. Since 2016, it has been successively approved for multiple indications including urothelial carcinoma, non-small cell lung cancer, and triple-negative breast cancer. It is an important drug in the field of cancer immunotherapy, with multiple clinical studies still ongoing. Avelumab: A fully human IgG1-λ immune checkpoint inhibitor targeting PD-L1, which may also exert effects through antibody-dependent cellular cytotoxicity (ADCC) . Approved for metastatic Merkel cell carcinoma in 2017, its indications later expanded to urinary tract cancer, renal cell carcinoma, etc., providing diversified treatment plans for advanced tumor patients. Moxetumomab pasudotox-tdfk: A recombinant immunotoxin composed of a murine scFv fused with a truncated Pseudomonas exotoxin, targeting CD22 antigen for the treatment of relapsed/refractory hairy cell leukemia. Approved in 2018, it is a typical case of optimizing antibody affinity using phage display technology, offering a new treatment option for patients with rare leukemia. 02 Autoimmune and Inflammatory Diseases Autoimmune and inflammatory diseases are often accompanied by immune system disorders. Traditional therapeutic drugs often have limitations such as limited efficacy and obvious side effects. This is the field where phage display technology first achieved brilliant results. By screening fully human antibodies, the technology reduces immunogenicity risks from the source, giving birth to the "blockbuster drug" in modern medical history and promoting the R&D of a series of precision-targeted drugs, which has completely changed the treatment pattern of autoimmune diseases and freed countless patients from the predicament of long-term dependence on hormones and poor efficacy. Adalimumab: The first fully human monoclonal antibody drug marketed through phage display technology, approved for rheumatoid arthritis in 2002. Targeting tumor necrosis factor-α (TNF-α), it requires no subsequent humanization modification and has excellent efficacy and safety. After its launch, it has become the gold standard for the treatment of various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. It topped the global drug sales list for more than a decade consecutively, with global sales still as high as approximately 14.4 billion US dollars in 2023, fully verifying the enormous commercial value of this technology. Belimumab: Approved in 2011, it is the first biological agent specifically used for the treatment of systemic lupus erythematosus. Targeting B cell-activating factor (BLyS), it controls the disease by inhibiting abnormally active B cells, demonstrating that phage display technology can tackle complex and intractable autoimmune disease targets. Guselkumab: A fully human IgG1-λ monoclonal antibody targeting the p19 subunit of IL-23, blocking the IL-23/Th17 pathway and inhibiting inflammatory responses. Approved for the treatment of moderate-to-severe plaque psoriasis in 2017, its indications later expanded to psoriatic arthritis, providing a precision treatment plan for autoimmune skin diseases and joint diseases. Ixekizumab: A humanized IgG4-κ monoclonal antibody targeting IL-17A, inhibiting pathological reactions mediated by inflammatory factors. Since 2016, it has been successively approved for indications such as psoriasis, psoriatic arthritis, and ankylosing spondylitis. It is an important drug in the field of autoimmune diseases, especially with significant efficacy in psoriasis treatment. Serplulimab: Approved in 2024, it is the first domestically independently developed and marketed fully human anti-IL-17A monoclonal antibody through phage display technology, used for the treatment of moderate-to-severe plaque psoriasis and ankylosing spondylitis. It took only about 17 months from the submission of the marketing application to approval, reflecting the maturity of China's full-chain capabilities on this technology platform and breaking the monopoly of foreign capital. 03 Infectious Diseases Faced with public health challenges such as emerging infectious diseases and drug-resistant bacterial infections, problems such as the long R&D cycle of traditional vaccines and drug resistance caused by antibiotic abuse have become increasingly prominent. The potential of antibodies as a "passive immunization" therapy has been fully realized through phage display technology. This technology can quickly screen high-affinity neutralizing antibodies without relying on the body's active immunity, and can be directly used for infection prevention or treatment. It is particularly suitable for scenarios such as immunocompromised populations and emergency response to emerging infectious diseases, providing a new and efficient solution for the prevention and control of infectious diseases. Raxibacumab: A fully human IgG1-λ monoclonal antibody targeting the protective antigen (PA) of Bacillus anthracis, neutralizing lethal toxins. Approved for the prevention and treatment of inhalational anthrax in 2012, it is an important drug for responding to bioterrorism, demonstrating the application value of phage display technology in the field of anti-infection. 04 Ophthalmic Diseases Ophthalmic diseases, especially fundus lesions, have long lacked effective treatment methods due to their special location and difficulty in drug penetration, putting many patients at risk of blindness. Antibody drugs derived from phage display technology have made important breakthroughs in the field of ophthalmology. By optimizing the size of antibody molecules (such as Fab fragments), they achieve efficient penetration and precise targeting of fundus lesion sites while ensuring safety. They provide effective treatment methods for blinding eye diseases such as wet age-related macular degeneration and diabetic macular edema, significantly improving patients' visual prognosis. Ranibizumab: A Fab antibody fragment targeting VEGF-A, inhibiting fundus neovascularization. Approved for the treatment of wet age-related macular degeneration in 2006, its indications later expanded to diabetic macular edema, retinal vein occlusion, etc. It is a benchmark drug for anti-VEGF therapy in ophthalmology, greatly improving patients' visual prognosis. 05 Hematological Diseases and Others In addition to common disease areas, the application of phage display technology continues to expand into more niche and intractable disease areas. For fields with "lack of medical treatment" such as rare diseases and hematological diseases, this technology has successfully broken through traditional R&D bottlenecks through flexible antibody format design (such as nanobodies) and efficient target screening capabilities, providing innovative solutions for these diseases. It enables niche patient groups to receive targeted treatment and fills the gap in clinical treatment. Caplacizumab: A humanized bivalent single variable domain antibody (VHH) targeting the A1 domain of von Willebrand factor (vWF), used for the treatment of acquired thrombotic thrombocytopenic purpura. Approved in 2018, it is the first nanobody drug, demonstrating the flexibility of phage display technology in developing new antibody formats. Emapalumab: A fully human IgG1-λ monoclonal antibody targeting IFNγ, inhibiting its downstream signaling, used for the treatment of refractory hemophagocytic lymphohistiocytosis. Approved in 2018, it provides a targeted treatment plan for rare immune disorders and is currently being explored for the treatment of diseases such as COVID-19. ▶ 04 Technological Innovation and Future Trends Phage display technology is continuously evolving through integration with cutting-edge science and technology. The in-depth integration of high-throughput automated platforms and artificial intelligence is reshaping the antibody discovery process. Automated systems have significantly shortened the screening cycle, while artificial intelligence has achieved a paradigm shift from "trial-and-error screening" to "rational design" by analyzing massive amounts of data. It can predict performance and even design new sequences from scratch, providing a new path for overcoming traditional challenges. The flexibility of this technology makes it an indispensable core tool for developing complex therapies such as bispecific antibodies and antibody-drug conjugates. It can effectively solve engineering challenges in multi-protein assembly and accelerate the birth of next-generation precision drugs. At the same time, the application scope of the technology is constantly expanding. Beyond traditional fields such as tumors and autoimmune diseases, researchers are actively exploring new therapeutic possibilities in antiviral, neurodegenerative diseases and even more cutting-edge directions. Through synergy with various innovative technologies, this classic platform continues to radiate new vitality and is expected to drive more breakthrough treatment plans in the future. ▶ Reference [1] Zhang Y. Evolution of phage display libraries for therapeutic antibody discovery. MAbs. 2023;15(1):2213793. doi:10.1080/19420862.2023.2213793 [2] Pung HS, Tye GJ, Leow CH, Ng WK, Lai NS. Generation of peptides using phage display technology for cancer diagnosis and molecular imaging. 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(2019) 84:255–63. doi: 10.1007/s00280-019-03875-6 [11] Jespers LS, Roberts A, Mahler SM, Winter G, Hoogenboom HR. Guiding the selection of human antibodies from phage display repertoires to a single epitope of an antigen. Biotechnology. (1994) 12:899–903. doi: 10.1038/nbt0994-899 [12] Blair HA, Duggan ST. Belimumab: a review in systemic lupus erythematosus. Drugs. (2018) 78:355–66. doi: 10.1007/s40265-018-0872-z [13] Nogueira M, Torres T. Guselkumab for the treatment of psoriasis–evidence to date. Drugs Context. (2019) 8:212594. doi: 10.7573/dic.212594 [14] Liu L, Lu J, Allan BW, Tang Y, Tetreault J, Chow CK, et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J Inflamm Res. (2016) 9:39–50. doi: 10.2147/JIR.S100940 [15] Shen P, Zhang T, Hao L, et al. Efficacy and safety of serplulimab in solid tumors: a meta-analysis[J]. Frontiers in Pharmacology, 2025, 16: 1604874. [16] Kummerfeldt CE. 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(2016) 127:1666–75. doi: 10.1182/blood-2015-12-684399 关于三优生物三优生物是一家以“让天下没有难做的创新生物药”为使命，以超万亿分子库和智能科技驱动的生物医药高科技企业。公司致力于打造全球顶尖的原创新药创新工场。公司以智能超万亿分子库（AI-STAL）为核心；以干湿结合、国际领先的创新生物药智能化及一体化研发平台为依托；以多样化的业务模式推动全球创新药物的研发及产业化。公司总部位于中国上海，在亚洲、北美洲、欧洲等多地建立了业务中心，形成了全球化的业务网络，现有投产及布局的研发及GMP场地20000多平方米。公司已与全球2000多家药企、生技公司等建立了良好的合作关系，已赋能1200多个新药研发项目；已完成50多个合作研发项目，其中10多个协同研发项目已推至IND及临床研发阶段。公司已申请130多项发明专利，其中30多项发明专利已获得授权，并获得了国家级高新技术企业、上海市专精特新、ISO9001、ISO27001等10余项资质及体系认证。推荐阅读三优十周年｜平台篇-抗体工程平台三优十周年｜平台篇-体外药效平台特应性皮炎：从免疫紊乱到精准靶向的治疗革命三优十周年｜抗衰老-从长生神药到系统与精准干预战略跃迁｜打造全球顶尖的原创新药创新工场三优十周年｜恶病质的代谢紊乱与靶向药物的研发态势三优十周年｜中国药企撬动千亿美元赛道三优十周年｜平台篇-创新抗体产生平台三优十周年｜眼科治疗前沿：用抗体药物精准点亮未来三优十周年｜磁阵列全人源小鼠抗体发现平台三优十周年｜新“药王”加冕：减重增肌三优十周年｜抗体药物如何实现精准“狙击”炎症？三优十周年｜血液肿瘤治疗革命-精准分层治疗新时代三优十周年｜抗体药免疫原性全方位解析三优十周年｜肿瘤免疫2025及2018双诺奖解析三优十周年｜TCE药物-重塑免疫治疗版图的新力量

抗体药物偶联物

2026-01-19

·规培小生聊科研

STTT重磅综述 | 从发病机制到干预靶点一文理清！

2025年，华中科技大学团队在《Signal Transduction and Targeted Therapy》发表综述《Deep insight into cytokine storm: from pathogenesis to treatment》。文章聚焦“细胞因子风暴（CS）”这一致死性全身炎症综合征，系统梳理其在暴发性心肌炎、ARDS、HLH、CAR-T相关CRS等急危重症中的共同致病机制、关键信号通路及靶向干预策略，旨在为临床提供精准识别与综合救治的循证框架。引言定义细胞因子风暴（CS）是免疫细胞过度激活、循环细胞因子急剧升高所致的危及生命的全身炎症综合征，表现为急性全身炎症、器官功能障碍和死亡。概念演进 1958 年：以“流感样综合征”描述病毒感染后的过度免疫应答 1991 年：提出“细胞因子释放综合征（CRS）” 1993 年：首次用“CS”命名 allo-HSCT 后的植入综合征核心通路/介质涉及 JAK/STAT、TLR、NLRP3 炎症小体、NETs 等信号轴；关键细胞因子包括 IL-1、IL-6、IL-18、TNF、IFN-γ 等；已有 HScore、MS score、EASIX 等预测模型。治疗现状已开发 IL-1、IL-6、IL-18、TNF、IFN-γ 单抗及 JAK、 caspase、钙调磷酸酶抑制剂等，但不同疾病的主导通路各异，需个体化干预。本文目的基于国际进展与作者团队研究，系统梳理 CS 的经典信号通路、关键免疫细胞与靶器官损伤模式，深入剖析 FM、ARDS、SIRS、HLH、aGVHD、CAR-T-CRS 中的 CS 特征与管理要点，并展望纳米海绵、MSC、血液净化、AI 预警等未来方向，为降低 CS 相关死亡率提供循证框架。CS中关键信号通路及相关细胞因子的作用JAK/STAT 通路核心构成：受体-JAKs（JAK1/2/3、TYK2）-STATs（STAT1-6） IL-6 驱动：mIL-6R/sIL-6R → gp130 → JAK/STAT3 → 放大 IL-1β、IL-8、CCL2/3/5、GM-CSF、VEGF TNF/IFN-γ：协同激活 JAK1 → STAT 磷酸化 → 促炎基因表达疾病关联：HLH、aGVHD、CAR-T-CRS、COVID-19、暴发性心肌炎均可见该通路过度活化治疗提示：JAK1 抑制剂（itacitinib 等）可减轻 CAR-T-CRS 及 COVID-19 ARDS；STAT3 抑制缓解病毒性心肌炎TLRs 通路模式识别：TLR3/4/7/8 识别 PAMPs/DAMPs → MyD88-MAPK（TNF/IL-1β/IL-6）与 TRIF-IRF3（Ⅰ型 IFN）双轨信号 COVID-19：S 蛋白结合 TLR4；重症患者 TLR3/4/7/9 高表达，NF-κB 过度激活病毒性心肌炎：CVB3 感染后全 TLR 上调，促心肌 IL-1/6、TNF、IFN 释放，形成正反馈损伤环干预策略：核酸结合微纤维清除 DAMPs/PAMPs，或靶向 TLR 信号中间体，抑制 CS 保护器官NETs 形成基本过程：中性粒细胞经 NETosis 释放 DNA-酶-颗粒复合物，捕获病原体并放大炎症促炎效应：NETs 经 TLR2/4 刺激巨噬细胞产生 IL-6、pro-IL-1β，促进 Th17 分化；COVID-19 中与 ALI/ARDS 及免疫血栓正相关心肌炎模型：抑制 NETs（PAD4 敲除或药物阻断）减轻 CVB3 诱导的心肌坏死与免疫细胞浸润调控节点：midkine-LRP1 轴驱动 NETosis，靶向该轴可缓解实验性自身免疫性心肌炎NLRP3 炎症小体双信号模型：① PRRs-NF-κB 上调 pro-IL-1β/18、NLRP3、pro-caspase-1；② 应激源触发 NLRP3-ASC-caspase-1 复合体 → 成熟 IL-1β/18 + GSDMD 介导焦亡正反馈环：IL-1β/18 结合 IL-1R1/IL-18R → 持续激活 NF-κB，放大炎症疾病关联： CAPS：NLRP3 功能获得性突变 >200 种，自发炎症小体激活，表现为发热、中性粒细胞增多、组织炎病毒性心肌炎：CVB3 感染体内外激活 NLRP3，加重心肌损伤 COVID-19：NLRP3 激活导致严重肺炎及神经系统并发症干预手段：IL-1R 拮抗剂（anakinra）、caspase-1 抑制剂、NLRP3 特异性阻断剂正在临床试用，减轻 CS 及器官损伤CS中细胞死亡与免疫细胞激活的作用Cell death in CS 多重死亡模式CS 中免疫细胞过度激活→大量细胞因子→触发坏死性凋亡、凋亡、焦亡、PANoptosis 等多种程序性死亡。坏死性凋亡（Necroptosis）病毒感染/严重炎症时激活；caspase-8 活性下降可抑制该通路并释放 IL-10，助于脓毒症免疫抑制期。凋亡（Apoptosis） SARS-CoV-2 通过 caspase-8 依赖的凋亡造成 COVID-19 肺损伤；维持稳态与清除病原体的关键方式。焦亡（Pyroptosis）促炎性程序死亡；SARS-CoV-2 编码产物可调控炎症小体、caspase、gasdermin 等核心组分，加剧 CS。 PANoptosis 由 PANoptosome 复合体（ZBP1、AIM2、RIPK1 等感应器）整合多通路死亡程序；TNF+IFN-γ 协同触发，参与流感、CoV 感染、脓毒症、HLH 等，阻断二者可保护小鼠免于多器官衰竭。 T 细胞亚群与功能 CD4⁺ Th：免疫调节；CD8⁺ CTL：直接杀伤并分泌促炎因子。 CTL 缺陷与 CS 穿孔素/颗粒泡运输基因缺陷→靶细胞无法清除→持续 DAMPs/PAMPs→与 APC 长时间交互→大量细胞因子（原发性/继发性 HLH 核心机制）。治疗应用体外扩增 CD8⁺ T 细胞的过继细胞疗法（含 CAR-T）已用于肿瘤，但可伴随 CRS，需严密监测。NK 细胞抗病毒/肿瘤及细胞因子分泌产生 IFN-γ、TNF、GM-CSF 等，放大 T 细胞、巨噬细胞、DC 活化；趋化因子 MIP-1α/β、CCL5、IL-8 招募髓系/效应淋巴细胞。功能缺陷→CS 穿孔素缺失同 CTL，导致持续免疫激活；IL-2/IL-15 为关键激活因子，重组 IL-15 可扩增 NK 并抗肿瘤转移。巨噬细胞 M1 型（促炎） IFN-γ/TNF 激活→分泌 IL-1β、IL-6、IL-12、IL-23、TNF、MIP-1 等→招募粒细胞、NK、Th1/Th17→抗感染但可引发 CS。 M2 型（抗炎/修复） M2a：IL-4/IL-13 驱动，参与组织修复；M2b：免疫复合物+TLR 激活，调节免疫；M2c：糖皮质激素/IL-10 诱导，促再生；M2d（TAM）：腺苷+TLR 信号，促肿瘤。失衡后果 M2 极化过度→病原清除障碍、T 细胞功能低下→持续刺激→炎症因子失控→CS；MAS 即为巨噬细胞过度活化典型例证。中性粒细胞一线募集与杀菌吞噬、脱颗粒、NETosis；释放 IL-1α/β、IL-6、IL-18、MIF 等促炎介质，并通过 azurocidin、CXCL10 调控单核/巨噬功能。 NETs 与 CS CVB3 心肌炎模型：早期耗竭中性粒或抑制 NETs→减少单核浸润与心功能恶化；COVID-19 中低密度中性粒易 NETosis，与微血栓、ARDS 密切相关。干预靶点阻断 NET 形成（PAD4 抑制剂、DNA 酶 I）或清除已释放 NETs，可减轻多器官损伤。B 细胞抗体依赖性病原清除 CAR-T 治疗后 B 细胞缺失→抗体生成减少→反复 PAMPs 刺激→持续炎症 cascade；病毒抗体亦可交叉反应自身抗原，诱发自身免疫性 CS。肥大细胞心脏主要 TNF 来源 CVB3 感染时释放 TNF、IL-1β、IL-10；干细胞因子促进其聚集→CCL2 介导 Ly6C^high 巨噬细胞浸润→心肌功能障碍与纤维化。嗜酸性粒细胞毒性颗粒蛋白介导损伤持续激活释放主要碱性蛋白、过氧化物酶等→组织损伤；与嗜酸性心肌炎、哮喘、高嗜酸综合征相关。调控因子与治疗 IL-5、IL-4、IL-13 驱动其增殖/募集；糖皮质激素传统应用，新型靶向 IL-5、IL-5R、IL-4/IL-13 的生物制剂已获批临床。CS所致靶器官损伤概述CS 常致多器官衰竭（心、肺、肾、肝、胃肠、CNS 等）；虽为继发性损伤，却直接决定死亡率。早期识别器官受累有助于及时干预。血管内皮高细胞因子（IL-1/6、TNF）→ 内皮激活、通透性↑ → 组织水肿、低灌注、低血压甚至休克激活凝血与补体系统，联合 NETs 促血小板聚集、微血栓形成，加重缺氧与器官缺血心脏暴发性心肌炎表现：心肌水肿、收缩力骤降、快速血流动力学恶化机制： IL-1 负性肌力；阻断 IL-1R（anakinra）可恢复收缩功能线粒体抑制 → ROS↑ → 氧化应激与细胞死亡 Ca²⁺稳态失衡、缝隙连接蛋白下调 → 房颤、室速/室颤等心律失常 CAR-T、COVID-19 相关 CS 亦常见心肌损伤、心衰、缺血事件肺细胞因子风暴→肺泡-毛细血管屏障破坏：肺泡塌陷、顺应性↓、肺血管阻力↑、换气功能障碍 IL-6 为核心：促免疫细胞浸润、自由基与蛋白酶释放→上皮/内皮损伤诱导肺泡细胞焦亡、减少纤维连接蛋白→细胞连接松散推动 Th17 分化→IL-17/22 进一步放大炎症结果：ARDS；需机械通气与抗炎/抗凝综合治疗骨髓高炎症（TNF、IFN-γ、IL-6 等）直接抑制 HSC 自我更新→贫血、白细胞与血小板减少 IL-1β 破坏骨髓微环境，促造血衰老；aGVHD、HLH 时 T 细胞/巨噬细胞过度激活→造血细胞被吞噬，骨髓衰竭不可逆肾脏急性肾损伤：氮质血症、少/无尿机制： Th17-IL-17/ TNF→内皮 NO↓、血管收缩；IFN-γ 激活肾素-血管紧张素-醛固酮系统→高血压、肾小球高压免疫血栓、DIC→肾微血栓形成、皮质坏死低心排、低氧、肝肾综合征进一步加重低灌注补体激活参与急性肾小球肾炎、AKI 及慢性糖尿病肾病等肝脏与胃肠道肝：急性肝炎→肝衰竭；IL-6 促急性期蛋白（SAA、CRP、纤维连接蛋白）→淀粉样变、补体与凝血级联激活→微血栓、DIC炎症小体-IL-1β 致肝细胞焦亡；NK-IFN-γ-STAT1 抑制肝再生；TNF 经 ROS-JNK 促凋亡/坏死胃肠道：恶心、呕吐、腹痛、腹泻、腹水、结肠炎；黏膜免疫血栓与毛细血管渗漏可致缺血/穿孔中枢神经系统脑炎/ICANS：脑水肿、认知障碍、癫痫、颅神经损害、昏迷等通路： IL-6/TNF 破坏血脑屏障→外周细胞因子入脑；小胶质细胞与星形胶质细胞激活→神经毒性因子释放补体与凝血异常→卒中、缺血坏死 BCMA-CAR-T 可伴帕金森样表现治疗：IL-1Ra（anakinra）具中枢穿透性，可减轻 CNS-CS不同疾病中CS的应对策略1. 暴发性心肌炎（FM）1.1 临床与免疫特征最重心肌炎类型：起病6-48 h内出现心原性休克、致死性心律失常；中国年报告3-5万例，青壮年多。细胞因子风暴证据：血清IL-1、IL-10、sST2、TNF、IFN-γ、MIP-1α等39种炎症因子显著升高 EMB见大量T细胞/巨噬细胞/嗜酸粒浸润，多器官（肝、肾、肺）同步衰竭免疫调节（激素+IVIG/细胞因子阻断）有效→证实CS是主要致死驱动1.2 发病机制（病毒-免疫-CS三联）病毒触发 → TLR3/4/7/9、NLRP3、NETs迅速激活中性粒细胞自招募环Cxcl2/3-Cxcr2轴持续招募外周中性粒→NETs形成→促炎巨噬细胞极化→心肌坏死放大巨噬细胞主导CCR2⁺炎性单核为浸润主体；分泌IL-1、MIP-2等维持趋化梯度。CCR2⁻/⁻或MIP-2R⁻/⁻小鼠病变减轻 T细胞失衡Th1/Th17(IL-17/21/IFN-γ)促损伤；Treg/Th2具保护。ICI-心肌炎以CD8⁺CTL为主，PD-1缺失模型再现嗜酸粒与特殊表型IL-17A/IFN-γ双敲→Th2偏移→致死嗜酸心肌炎；VSA（变异型心绞痛）亦发现心肌炎-痉挛-激素有效三联1.3 救治方案（同济“生命支持-免疫调节-抗病毒”三合一）阶段核心措施剂量/要点证据生命支持 IABP→VA-ECMO IABP升SBP>20 mmHg、降HR 20-30 bpm；若循环仍不稳立即ECMO 多中心研究住院死亡率↓ 呼吸/肾/起搏 NIV→有创通气；CRRT；临时起搏器同步处理多器官免疫调节甲强龙 200-400 mg/d×3-5 d 抑制TLR-下游、促EET-IFN-γ抗病毒 IVIG 20 g/d×3-5 d（或1-2 g/kg） Fc段诱导M2极化、中和细胞因子抗病毒奥司他韦 75 mg bid×5 d（病毒±）神经氨酸酶抑制→减少心肌酶二次损伤禁忌单纯淋巴毒药物环孢素/硫唑嘌呤→不改善生存心肌炎治疗试验阴性2. 病毒性肺炎-ARDS2.1 免疫病理病毒（SARS-CoV-2、H1N1、H5N1）→Ⅰ型IFN延迟+IL-6/IL-1β/TNF风暴→内皮-上皮屏障崩溃、微血栓、ARDS JAK-STAT、NLRP3、补体、NETs四轴协同；IL-6为关键节点：促Th17、抑制纤维连接蛋白、放大焦亡2.2 循证干预药物/措施适应证/用法获益地塞米松 6 mg d×7-10 d（氧疗±机械通气） RECOVERY、CoDEX：28 d死亡率↓ 托珠单抗 8 mg/kg≤800 mg×1-2次；危重症联合激素 IL-6R阻断→DIC、MV需求↓ JAK抑制剂 Baricitinib 4 mg d×14 d ACTT-2：康复时间缩短；兼顾抗病毒抗病毒基础奥司他韦、帕拉米韦、RNA聚合酶抑制剂早期使用降低病毒载量抗凝低分子肝素（标准-治疗量按D-二聚体）减少肺微血栓血浆置换/吸附重症CS清除细胞因子小样本快速改善氧合 3. 脓毒症-SIRS3.1 机制 LPS-TLR4-MyD88→TNF-IL-1-IL-6级联；C5a受体上调→内皮渗漏；线粒体抑制-NO↑→心肌抑制、休克、DIC3.2 关键策略 1 h内抗生素+感染源控制；动态监测IL-6、PCT、HMGB-1 激素：氢化可的松200 mg/d持续输注×7 d（ADRENAL方案）→缩短MV时间乌司他丁：大剂量抑制溶酶体酶与氧自由基，阻断细胞因子靶向生物制剂：抗-TNF、IL-1Ra、抗-LPS单抗（试验阶段）免疫调节：TNFR2激动剂扩Treg、恢复免疫稳态4. 噬血细胞淋巴组织细胞增多症（HLH）4.1 分型与驱动原发性：穿孔素、Munc13-4、STXBP2等突变→CTL/NK细胞毒缺陷→IFN-γ持续↑ 继发性：感染（EBV最常见）、肿瘤、GVHD、CAR-T；PRF1低表达亦参与4.2 诊治流程时间 HLH-94/2004经典方案新兴靶向诱导 VP-16+地米；CsA可推迟至维持 Ruxolitinib（JAK1/2）、Anakinra（IL-1R）、Emapalumab（IFN-γ单抗）挽救 DEP（多柔比星脂质体+VP-16+甲强龙）±门冬阿仑单抗（CD52）、IL-18抗体、JAK抑制剂根治 allo-HSCT（原发性唯一治愈）基因疗法（PRF1、Munc13-4、SAP自体HSC编辑）临床前5. CAR-T细胞相关CRS5.1 发病链 CAR-T-CD40L ↔ 巨噬细胞-CD40 → IL-6/IL-1/IFN-γ+儿茶酚胺自放大环 → 内皮激活-DIC-多器官损伤预测：EASIX（LDH×Cr/PLT）>4.67、Ang-2、ST2、NETs↑；24-48 h内识别重度CRS5.2 分级管理（ASTCT 1-4级）等级首选用法备注 1-2级支持+监测可考虑托珠单抗预干预 ≥3级托珠单抗8 mg/kg（≤800 mg）×1-2次；同步地塞米松10 mg q6h×1-3 d 激素无效→siltuximab/阿那白滞素激素难治 JAK抑制剂（ruxolitinib）、GM-CSF抑制剂、TNF单抗、血浆置换、CRRT 维持CAR-T抗肿瘤效应6. allo-HSCT后aGVHD6.1 时相与机制预处理→DAMPs/PAMPs-TLR → 宿主APC激活 → 供体T细胞识别allo-抗原 → 迁移至皮肤/肝/肠 → 释放TNF/IL-1β/IFN-γ/CCLs → 组织损伤与CS6.2 预防-监测-治疗预防：CNI+MTX±ATG；北京方案（ATG+G-CSF）或移植后环磷酰胺；Abatacept（共刺激阻断）获批预测：SA/PA<0.731、MAGIC算法（ST2+REG3α+TNFR1）、Ang-II、CD4⁺CD8⁺双阳性T细胞、Tim-3⁺CD8⁺T细胞一线：甲强松1-2 mg/kg/d 激素难治：Ruxolitinib（FDA批准）、JAK/IL-6R/TNF双重阻断、MSC输注、USP11抑制剂、糖酵解抑制剂+激素（保持GVL）阻断CS的治疗前景 > 快速诊断 + 精准中和细胞因子 + 小分子/生物材料/血液净化多管齐下，未来 CS 治疗将走向“早预警-多靶点-可调控”一体化。1. 快速诊断新工具 sST2 即时检测试剂盒血清 sST2 水平与暴发性心肌炎（FM）进展高度相关，床旁 15 min 出结果，已在多中心验证。多因子 POCT 芯片IL-6/IFN-γ/GM-CSF/TNF 四合一微流控卡，用于 CAR-T 回输后 0-24 h 预警重度 CRS。 AI-预警模型整合电子病历 + 实时细胞因子 + 生命体征，深度学习预测 CS 风险（AUC>0.92），正在 ICU 试点。2. 靶向细胞因子/通路疗法靶点代表药物适应证/进展关键数据 IL-1α/β Anakinra（IL-1Ra） FM、ICANS、CRS、风湿性CS 退热<24 h，CRP↓70%，FM 28 d 死亡率↓（回顾性 n=98） IL-1β Canakinumab 病毒性心肌炎小鼠→胶原容积↓40% Ⅱ期试验筹备中 IL-6R Tocilizumab CAR-T-CRS、COVID-19、HLH Grade≥3 CRS 发生率 31%→15%，维持CAR-T抗瘤活性 IFN-γ Emapalumab 难治/复发 HLH（FDA 2018）总反应率 63%，6 个月生存 52% IL-18 Tadekinig alfa 成人 sHLHⅠ期安全，IL-18BP 校正后炎症积分↓ Ⅱ期招募中 TNF Infliximab 激素难治 aGVHD、MAS 联合 IL-6R 阻断可挽救 lethal-GVHD 小鼠并保留 GVL JAK1/2 Ruxolitinib aGVHD、HLH、COVID-19 ORR 82%，激素-sparing；Baricitinib 缩短 COVID-19 康复 1 天3. 小分子与信号干预 JAK 家族抑制剂 Tofacitinib、Upadacitinib：口服，已获批 RA、sJIA，正扩展至 HLH、CAR-T-ICANS。选择性 JAK1 抑制剂（Itacitinib）→阻断 IL-6/IFN-γ 信号，减少机会感染 vs 泛 JAK。 NLRP3 炎症小体抑制剂 MCC950、Dapansutrile：鼠 HLH/ARDS 模型中 IL-1β↓70%，生存延长；Ⅰ期健康人安全完成。 TYK2 变构抑制剂 Deucravacitinib：同时抑制 IFN-α/IL-12/IL-23 轴，计划启动 CS Ⅱ期。4. 生物材料与细胞治疗4.1 细胞因子纳米海绵（CNS）制备：膜蛋白保留的巨噬细胞-中性粒细胞膜包裹 PLGA 核。机制：表面呈现 IL-1R、IL-6R、TNFR 等，体内“诱骗”细胞因子→血浓度↓60-80%。疗效： HLH 小鼠：体温、铁蛋白、器官损伤显著改善，生存率 0→60%。可负载 JAK 抑制剂→协同缓释，降低单药剂量 5 倍。4.2 间充质干细胞（MSC）免疫重构：诱导 M2 巨噬细胞、Treg↑，抑制 DC 成熟；分泌 PGE2、TGF-β、HGF、IDO 多重抑炎。临床快照： ≥1000 项注册试验；COVID-19 ARDS（N=60）MSC 组 28 d 死亡率 7% vs 对照 24%。基因编辑 MSC（IL-10-过表达/IFN-γR-敲除）增强疗效，已提交 IND。4.3 血液净化-吸附柱柱类型吸附对象研究亮点 β2-微球蛋白柱 IL-1β、IL-6、TNF 脓毒症-CS 患者 4 h 后 IL-6↓50%，28 d 死亡率↓趋势 PMX-B 纤维柱内毒素脓毒休克 2 h 内血压回升，去甲肾上腺素用量↓30% NOA-001 新柱细胞因子+活化中性粒 ALI 兔模型：PaO₂/FiO₂↑90%，NETs↓60%，拟进入Ⅰ期5. 基因与RNA 技术 CRISPR-Cas9 体内编辑小鼠 HLH：尾静脉注射 AAV-PRF1-saCas9 修复 >30% HSC，恢复穿孔素表达，IFN-γ↓70%，长期造血重建。 siRNA 脂质纳米颗粒靶向 NLRP3 或 TYK2 的 siRNA-LNP（0.3 mg/kg）单次静注→ARDS 鼠肺 IL-1β↓80%，生存率↑2 倍。 mRNA 瞬时表达体外转录 IL-10-mRNA-LNP 促进 M2 极化，用于 MSC 预处理，增强免疫抑制 3 倍。 6. 未来展望 “omics+AI”精准预测：单细胞转录组+蛋白组实时描绘 CS 免疫图谱→个体化靶点自动生成。可编程纳米药物：pH/ROS 响应型载体实现炎症部位“0-1”释放，降低全身毒性。器官-芯片-仿生灌流：同步监测心肌/肺/肝 3D 芯片细胞因子，高通量筛选联合方案。异种器官与人工体外支持：基因编辑猪心-肾、3D 生物打印肝脏，为终末期 CS 器官替代提供新供源。治疗诱导 CS 预警：CAR-T、双特异抗体、免疫激动剂用药前遗传-免疫评分，提前部署 IL-1Ra/纳米海绵防护。 > 结论：从单靶点抗体到多模式细胞/材料/基因技术，CS 治疗正迈向“早识别-多通路-可调控”的精准时代；未来 5 年内，联合“纳米海绵+MSC+JAKi”方案有望在重症 COVID-19、HLH、CAR-T-CRS 中率先落地。结论与展望 > 细胞因子风暴（CS）是“原发性疾病-急性全身炎症-继发性器官失代偿”三位一体的致死闭环；唯有“早预警-多靶点-个体化-多学科”整合模式，才能突破高死亡率瓶颈。1. 当前困境与三大核心原则困境应对原则具体内涵起病急、进展快、死亡率高全面整合治疗分子-细胞-器官-系统多层干预；药物+生命支持+多学科并行不同疾病主导通路各异锁定关键介质 TLR/JAK/NLRP3/NETs 通路谱系化；避免“错靶”加重炎症老药 off-target 毒性大精准低毒疗法二代高选择性抑制剂/生物材料/基因编辑，减少感染-血液学毒性2. 技术融合路线图2.1 多组学 + AI → 早预警单细胞转录组+蛋白组+代谢组实时绘制 CS 免疫图谱深度学习模型整合 EHR+影像+细胞因子，0-6 h 预测重症 CS（AUC>0.92） **数字孪生患者(Digital Twin)**模拟不同干预结局，指导床旁决策2.2 下一代靶向药物世代代表选择性临床状态亮点 1st Toc/rux 泛 JAK 已获批疗效确定，感染/血细胞减少 2nd Itacitinib(JAK1) JAK1>>JAK2 Ⅲ期保留抗病毒 IFN-λ，机会感染↓ 3rd Deucravacitinib(TYK2) 变构抑制 Ⅱ期阻断 IL-12/23-IFN-α 轴，肝毒性低未来 NLRP3-PROTAC 蛋白降解临床前可逆“开关”，避免长期免疫抑制2.3 生物材料“细胞因子海绵” **巨噬细胞膜纳米颗粒(LMNP)**：一次静注中和 15+ 细胞因子，HLH 小鼠生存率 0→60% pH/ROS 双响应脂质体：炎症部位定点释放 JAK 抑制剂，肾毒性↓5 倍 3D 打印吸附柱：β2-M/PMX-B/NOA-001 串联，同时清除细胞因子+NETs+内毒素，ARDS 兔 PaO₂/FiO₂↑90%2.4 基因与RNA 技术 CRISPR-Cas9 体内编辑：AAV-PRF1 修复 HLH 小鼠 HSC>30%，IFN-γ↓70%，长期造血重建 **siRNA-LNP(TYK2/NLRP3)**：单次静注 0.3 mg/kg，ARDS 模型肺 IL-1β↓80%，生存↑2 倍 mRNA-MSC：IL-10 mRNA 预编程 MSC，抑炎能力↑3 倍，已提交 IND2.5 器官替代与生命支持 2.0 基因编辑猪心-肾：10 基因敲除克服超急排斥，全球首例活体移植 60 天无 CS 发作器官芯片-仿生灌流：心-肺-肝 3D 芯片同步实时监测细胞因子，高通量筛选联合方案 AI-ECMO：闭环算法依据 IL-6/乳酸/血流动力学自动调节流量，减少 ECMO-CS 发生率3. 未来 5-10 年展望 0-1 h 预警-干预闭环AI 预测→POCT 细胞因子→纳米海绵/选择性 JAK1 抑制剂床旁自动给药，阻断“炎症风暴窗口”。 “一击多靶”联合包纳米海绵+MSC+二代 JAK 抑制剂三合一制剂，重症 COVID-19、HLH、CAR-T-CRS Ⅲ期注册。基因-细胞-材料融合CRISPR 修复 HSC+MSC-mRNA+可降解吸附柱，实现“根治-替代-清除”一体化 CS 平台。治疗诱导 CS 零发生率CAR-T、双特异抗体、免疫激动剂用药前遗传-免疫评分，提前部署 IL-1Ra/纳米海绵防护。全球多学科云网络5G+AI 实时共享 CS 生物标志物与影像，跨洲专家同步决策，缩短“诊断-用药-器官支持”时间至 <30 min。4. 结语从“单靶点抗体”到“多模式细胞/材料/基因”技术，CS 治疗正迈向早识别-多通路-可调控的精准时代。下一代目标：让细胞因子风暴在发生前就被“智能免疫防火墙”自动扑灭，把死亡率从 >30% 降至 <5%。

细胞疗法免疫疗法临床研究

2026-01-15

·PRNewswire

Hemophagocytic Lymphohistiocytosis Market Poised for Phenomenal Expansion in the US at a CAGR of 24.5% During the Forecast Period (2025-2034) | DelveInsight

The hemophagocytic lymphohistiocytosis market is expected to increase due to the launch of emerging therapies, such as plonmarlimab (TJ Biopharma), ELA026 (Electra Therapeutics), MAS825 (Novartis), tadekinig alfa (r-hIL-18BP) (AB2 Bio), and others, as well as label expansions of current therapies. This is because of the higher patient burden, approval of newer therapies with high cost, and broader acceptance and availability of newly approved therapies. LAS VEGAS, Jan. 15, 2026 /PRNewswire/ -- DelveInsight's Hemophagocytic Lymphohistiocytosis Market Insights report includes a comprehensive understanding of current treatment practices, hemophagocytic lymphohistiocytosis emerging drugs, market share of individual therapies, and current and forecasted market size from 2020 to 2034, segmented into leading markets [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Hemophagocytic Lymphohistiocytosis Market Summary The market size for hemophagocytic lymphohistiocytosis was found to be USD 140 million in the United States in 2024. The HLH market remains highly unmet, with conventional therapies leading to high mortality (20–30% before HSCT) and only about 60% long-term survival due to toxicity, treatment failure, and relapse risk. Among the 7MM countries, there were 5,100 incident cases of HLH in the US in 2024. Leading hemophagocytic lymphohistiocytosis companies, such as TJ Biopharma, AB2 Bio, Electra Therapeutics, Novartis, and others, are developing new hemophagocytic lymphohistiocytosis treatment drugs that can be available in the hemophagocytic lymphohistiocytosis market in the coming years. The promising hemophagocytic lymphohistiocytosis therapies in clinical trials include Plonmarlimab (TJM2/TJ003234), Tadekinig alfa (r-hIL-18BP), ELA026, MAS 825, and others. Discover the new hemophagocytic lymphohistiocytosis treatment @ Key Factors Driving the Growth of the Hemophagocytic Lymphohistiocytosis Market Rising HLH Incidence: The increasing incidence of HLH, often triggered by underlying infections, autoimmune diseases, malignancies, or immuno-oncology treatments, has expanded the pool of patients needing diagnosis and therapy. Advances in Diagnostics and Early Detection: Improvements in diagnostic technologies, including genetic testing, immunologic profiling, and next-generation sequencing, enable earlier and more accurate detection of HLH. This allows timely intervention, which is critical given the rapid, life-threatening course of HLH. GAMIFANT Maintains First-in-Class Position in HLH: GAMIFANT (Sobi) remains the only approved therapy for primary HLH (since 2018) and has recently expanded its label, gaining US FDA approval in June 2025 for MAS associated with Still's disease. Following this approval, GAMIFANT has demonstrated stronger-than-projected market uptake, with double-digit growth in Constant Exchange Rates (CER). The company plans to pursue EU regulatory submission in 2026, indicating continued strategic expansion of its HLH and MAS portfolio. Launch of Emerging HLH Drugs: The dynamics of the HLH market are expected to change in the coming years due to the launch of emerging therapies such as plonmarlimab (TJ Biopharma), ELA026 (Electra Therapeutics), MAS825 (Novartis), tadekinig alfa (r-hIL-18BP) (AB2 Bio), and others. Hemophagocytic Lymphohistiocytosis Market Analysis Management of HLH necessitates a comprehensive, multimodal strategy that integrates immunosuppressive, cytotoxic, and targeted therapies to control hyperinflammation, limit pathological immune activation, and restore immune homeostasis. Therapeutic decisions are guided by disease severity and the underlying trigger, with early, aggressive intervention essential to prevent irreversible organ damage. High-dose corticosteroids, particularly dexamethasone, constitute a foundational component of HLH treatment due to their potent anti-inflammatory effects and ability to suppress cytokine-mediated tissue injury. Etoposide-based regimens remain a cornerstone of first-line therapy, as they effectively eradicate cytotoxic lymphocytes and macrophages that are excessively activated and drive disease pathology. Immunosuppressive agents such as cyclosporine are commonly employed to suppress T-cell activation and reduce cytokine release, thereby dampening immune overactivation. Targeted biologic therapies, including rituximab for EBV-associated HLH and monoclonal antibodies such as alemtuzumab or antithymocyte globulin in refractory disease, enable more selective immune modulation. When infections serve as triggering factors, concurrent antimicrobial therapy, including antivirals and antibiotics, is critical to address both the precipitating cause and the downstream inflammatory cascade. Collectively, these treatment approaches aim to achieve disease stabilization and control, allowing eligible patients to proceed to definitive curative options such as hematopoietic stem cell transplantation (HSCT). GAMIFANT demonstrated strong commercial momentum in Q3 2025, generating USD 66.6 million in revenue, a 98% year-over-year increase. Revenue growth was driven by rising patient adoption, a favorable product mix, and the successful U.S. launch for macrophage activation syndrome (MAS) in Still's disease, making GAMIFANT the first approved therapy for both pediatric and adult patients. This milestone highlights GAMIFANT's broader applicability across the HLH–MAS disease spectrum and reinforces its long-term growth potential. Regulatory momentum remains positive, while active compassionate-use programs in Europe continue to reflect sustained clinician demand. Looking ahead, GAMIFANT revenues are expected to grow at a low double-digit CAGR at constant exchange rates, supported by global market expansion, improved patient access, and continued uptake across both MAS and HLH indications. Hemophagocytic Lymphohistiocytosis Competitive Landscape The pipeline of HLH is very scarce, with only three emerging therapies: plonmarlimab (TJ Biopharma), ELA026 (Electra Therapeutics), MAS825 (Novartis), and tadekinig alfa (r-hIL-18BP) (AB2 Bio). Despite all being in late-stage development, this underscores the scarcity of therapeutic innovation in this space. AB2 Bio's Tadekinig alfa is an innovative recombinant human IL-18 binding protein (IL-18BP) that neutralizes IL-18, a key pro-inflammatory cytokine. Under normal physiological conditions, endogenous IL-18BP is present in excess, maintaining circulating free IL-18 at undetectable levels. In certain autoinflammatory disorders, this regulatory balance is disrupted, leading to elevated systemic free IL-18 and severe pathological hyperinflammation. Tadekinig alfa re-establishes this balance by sequestering excess free IL-18, thereby attenuating inflammatory responses. This mechanism represents a novel and promising therapeutic strategy for autoimmune and inflammatory diseases characterized by elevated systemic IL-18 levels. The therapy is currently being evaluated in a Phase III clinical trial. Electra Therapeutics' ELA026 is a monoclonal antibody developed to treat severe inflammatory diseases driven by dysregulated myeloid cells and T-lymphocytes. It selectively and rapidly depletes the circulating inflammatory myeloid cells and T cells responsible for disease pathology, while preserving the CD47/SIRPα immune checkpoint pathway. ELA026 is presently in Phase II/III clinical development. The anticipated launch of these emerging therapies are poised to transform the hemophagocytic lymphohistiocytosis market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the hemophagocytic lymphohistiocytosis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. Discover more about the hemophagocytic lymphohistiocytosis drugs @ Hemophagocytic Lymphohistiocytosis Drugs Market Recent Developments in the Hemophagocytic Lymphohistiocytosis Market In October 2025, Electra Therapeutics announced that the first patients had been dosed in the SURPASS study, a pivotal Phase II/III clinical trial evaluating ELA026, the first investigational therapy designed to broadly treat secondary HLH. In June 2025, Sobi announced that the US FDA approved emapalumab for the treatment of adult and pediatric (newborn and older) patients with HLH/MAS in known or suspected Still's disease, including sJIA, with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS. What is Hemophagocytic Lymphohistiocytosis? Hemophagocytic lymphohistiocytosis is a rare, life-threatening immune system disorder characterized by extreme and uncontrolled immune activation. In HLH, immune cells, particularly macrophages and lymphocytes, become overactive and release excessive amounts of inflammatory cytokines, leading to a "cytokine storm" that causes widespread tissue damage and organ failure. The condition can be inherited (primary HLH) due to genetic defects affecting immune regulation, or acquired (secondary HLH) and triggered by infections, malignancies, autoimmune diseases, or other immune challenges. Clinically, HLH often presents with persistent high fever, enlarged liver and spleen, cytopenias, liver dysfunction, and markedly elevated inflammatory markers. Without prompt diagnosis and treatment, HLH can rapidly progress and is frequently fatal. Hemophagocytic Lymphohistiocytosis Epidemiology Segmentation The hemophagocytic lymphohistiocytosis epidemiology section provides insights into the historical and current hemophagocytic lymphohistiocytosis patient pool and forecasted trends for the leading markets. The commonest single disease entities were lymphoma, SLE, and sJIA. There has been evidence of clinically diagnosed HIV, EBV, or CMV infection either in the health record or on the death certificate in 2.3%, 8.9%, and 3.3%, respectively. The hemophagocytic lymphohistiocytosis treatment market report proffers epidemiological analysis for the study period 2020–2034 in the leading markets, segmented into: Total Incident Cases of HLH Total Incident Cases of HLH by Type Incident Cases of HLH by Gender Incident Cases of Familial HLH by Mutation Incident Cases of Acquired HLH by Etiology Total Treated Cases of HLH Scope of the Hemophagocytic Lymphohistiocytosis Market Report Therapeutic Assessment: Hemophagocytic Lymphohistiocytosis current marketed and emerging therapies Hemophagocytic Lymphohistiocytosis Market Dynamics: Key Market Forecast Assumptions of Emerging Hemophagocytic Lymphohistiocytosis Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Hemophagocytic Lymphohistiocytosis Market Access and Reimbursement Download the report to understand what is the latest research on hemophagocytic lymphohistiocytosis @ New Hemophagocytic Lymphohistiocytosis Medication Table of Contents Related Reports Hemophagocytic Lymphohistiocytosis Clinical Trial Analysis Hemophagocytic Lymphohistiocytosis Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key HLH companies, including Chia Tai Tianqing Pharmaceutical Group, Bellicum Pharmaceuticals, Atara Biotherapeutics, Incyte Corporation, Alpine Immune Sciences, Expression Therapeutics, among others. Systemic Lupus Erythematosus Market Systemic Lupus Erythematosus Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key SLE companies, including Biogen, Novartis, MorphoSys, Idorsia Pharmaceuticals, Viatris, RemeGen, UCB Pharma, Genentech, Bristol Myers Squibb, AbbVie, among others. Systemic Lupus Erythematosus Clinical Trial Analysis Systemic Lupus Erythematosus Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key SLE companies, including Roche, Biogen, Viatris Inc., Novartis, Qilu Pharmaceutical, ImmuPharma, Beijing Mabworks Biotech Co., Ltd., Zenas Biopharma, AbbVie, Beijing InnoCare Pharma Tech Co., Ltd., Alumis Inc., Galapagos NV, Palleon Pharmaceuticals, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Johnson & Johnson, Merck KGaA, Resolve Therapeutics, ILTOO Pharma, Argenx, Cartesian Therapeutics, Keymed Biosciences Co.Ltd, BioSenic, Eisai, Vertex Pharmaceuticals, Kyverna Therapeutics, Miltenyi Biomedicine, Astrazeneca, Otsuka Pharmaceutical, Fresh Tracks Therapeutics, among others. Macrophage Activation Syndrome Market Macrophage Activation Syndrome Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key MAS companies, including Electra Therapeutics, TJ Biopharma, AB2 Bio, Novartis, Deepcure, Sobi, 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 . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP 21% more press release views with Request a Demo

上市批准免疫疗法临床3期

100 项与依马利尤单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	依马利尤单抗	L04AA39	DB14724

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
巨噬细胞活化综合征	美国	NovImmune SA	2025-06-27
全身型幼年特发性关节炎	美国	NovImmune SA	2025-06-27
噬血细胞性淋巴组织细胞增多症	美国	NovImmune SA	2018-11-20

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
免疫系统疾病	申请上市	欧盟	Swedish Orphan Biovitrum AB	2020-07-23
多关节型幼年特发性关节炎	临床3期	美国	苏庇医药（广州）有限公司	2022-01-14
多关节型幼年特发性关节炎	临床3期	日本	苏庇医药（广州）有限公司	2022-01-14
多关节型幼年特发性关节炎	临床3期	比利时	苏庇医药（广州）有限公司	2022-01-14
多关节型幼年特发性关节炎	临床3期	加拿大	苏庇医药（广州）有限公司	2022-01-14
多关节型幼年特发性关节炎	临床3期	捷克	苏庇医药（广州）有限公司	2022-01-14
多关节型幼年特发性关节炎	临床3期	法国	苏庇医药（广州）有限公司	2022-01-14
多关节型幼年特发性关节炎	临床3期	德国	苏庇医药（广州）有限公司	2022-01-14
多关节型幼年特发性关节炎	临床3期	意大利	苏庇医药（广州）有限公司	2022-01-14
多关节型幼年特发性关节炎	临床3期	荷兰	苏庇医药（广州）有限公司	2022-01-14

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03311854 (NI-0501-06, ACR2025)	临床2期	巨噬细胞活化综合征	39	Emapalumab	憲積襯鑰鬱廠廠廠繭蓋(觸觸網鹹壓鹹壓網鑰選) = 鑰廠構選餘繭鹹淵憲網鬱廠衊憲範淵夢夢鏇願 (繭齋膚鬱築選選觸衊艱, 37.2 ~ 69.9) 更多	积极	2025-10-24
NCT03311854 (NI-0501-06, ACR2025)	临床2期	巨噬细胞活化综合征	39	Emapalumab (EMERALD (NCT05001737))	遞憲製築觸網簾製窪範(鏇衊鏇觸繭餘製鑰鹹衊) = 遞衊顧艱餘憲範選遞願繭窪鬱艱鏇顧鏇壓鏇製 (艱襯構蓋淵艱蓋憲獵襯 ) 更多	积极	2025-10-24
NCT03311854 (NI-0501-06, ACR2025)	临床2期	巨噬细胞活化综合征	39	Emapalumab (NI-0501-06 (NCT03311854))	窪簾築網構廠鹹選窪願(淵鑰鏇鏇艱窪衊鬱繭遞) = 獵衊醖鬱製廠鑰齋願遞顧鬱廠窪鹹構鑰簾衊廠 (願鬱選衊齋憲鹹選顧艱 )	积极	2025-10-24
NCT03311854 \| NCT05001737 (NI-0501-14, FDA_CDER) 人工标引	N/A	全身型幼年特发性关节炎 \| 噬血细胞性淋巴组织细胞增多症 \| 巨噬细胞活化综合征	39	GAMIFANT	糧窪繭艱範築窪廠膚壓(遞壓醖壓窪蓋窪窪窪鬱) = 遞夢廠製衊鬱製遞餘構糧艱衊願衊選醖選選觸 (衊獵繭糧獵壓廠淵積糧, 37.2 ~ 69.9) 更多	积极	2025-06-27
NCT03311854 (NI-0501-06, EULAR2025)	临床2期	巨噬细胞活化综合征	39	Emapalumab (MAS in Still's disease + Inadequate response to high-dose glucocorticoids)	鏇積鑰壓顧艱範鹹製範(糧網觸襯鏇蓋醖醖顧壓) = 範淵積窪鬱餘簾襯網顧製鑰鏇糧夢鏇顧遞獵網 (餘醖製獵淵廠簾蓋憲憲 )	积极	2025-06-11
PS2153 (EHA2025)	N/A	细胞因子释放综合征 IFN-γ \| TNF-α \| IL-2 ... 更多	38	Emapalumab	獵窪窪膚襯構憲簾窪夢(齋鹹糧獵齋繭積範膚糧) = 8 patients died (2 from disease relapse/progression, 4 from severe infections, and 2 from septic shock associated with CRS) 範艱繭夢選鬱齋積願夢 (製廠壓範積衊夢壓壓壓 ) 更多	积极	2025-05-14
NCT03311854 (NI-0501-06, ACR2024)	临床3期	心血管疾病	39	Emapalumab	醖鬱醖夢壓膚遞積構獵(鏇窪願觸壓糧鬱範鹹遞) = 選蓋衊遞蓋艱窪壓艱壓衊餘鬱鏇簾鑰餘顧繭鹽 (顧築獵窪積糧蓋醖鏇艱, 37.2 ~ 69.9) 更多	积极	2024-11-10
NCT04731298 (P449, CTgov)	临床2期	移植物功能障碍	2	Emapalumab (Emapalumab Treated)	蓋襯簾鬱鏇獵淵築鏇糧 = 齋觸艱積淵廠餘鬱艱襯廠鏇構夢淵廠艱積鏇餘 (範願鏇憲製鹹顧觸襯廠, 觸襯艱淵齋積襯構糧艱 ~ 網醖繭糧淵廠鬱襯範觸) 更多	-	2023-12-28
NCT04731298 (P449, CTgov)	临床2期	移植物功能障碍	2	emapalumab (Non-emapalumab Treated)	蓋襯簾鬱鏇獵淵築鏇糧 = 網鏇齋蓋構淵範鹹糧願廠鏇構夢淵廠艱積鏇餘 (範願鏇憲製鹹顧觸襯廠, 窪襯選觸夢鬱蓋餘窪鏇 ~ 築醖艱鏇糧鑰餘觸簾糧) 更多	-	2023-12-28
NCT04765553 (CTgov)	临床1期	罕见病	8	NI-0501 (Emapalumab)	鬱襯繭範觸構襯構遞鏇(範鏇簾衊餘願鹽選鑰選) = 築鏇鑰糧繭衊窪艱夢鬱鹽衊構簾糧醖繭簾糧壓 (觸觸齋繭齋獵醖顧鹽衊, 網鹹製艱憲構膚鑰鏇齋 ~ 壓醖膚蓋衊願醖願鹽積) 更多	-	2023-11-24
NCT04765553 (CTgov)	临床1期	罕见病	8	Saline (Placebo)	鏇蓋觸鹹醖鑰廠憲構築 = 願鏇醖築簾繭獵遞積遞憲齋觸製艱願繭廠構鹽 (積鹹齋構鑰衊膚築艱鏇, 鑰鑰網顧醖構淵遞構繭 ~ 構範壓觸築衊襯齋獵蓋) 更多	-	2023-11-24
NCT03985423 (CTgov)	临床2/3期	噬血细胞性淋巴组织细胞增多症	7	Emapalumab-Lzsg	艱憲積構餘淵壓繭構鏇(淵夢淵選鹹願餘襯壓淵) = 膚築選範廠繭構衊鹽鏇鹹鏇廠壓壓觸廠淵膚膚 (鹽艱鏇獵糧繭齋遞窪鏇, 鬱願顧鬱願鬱憲餘衊壓 ~ 壓衊襯憲願鏇願繭簾廠) 更多	-	2023-10-06
EBMT2023	临床2期	IFNÎ³ \| CXCL9	1	Emapalumab 3 mg/kg	簾簾餘憲築鬱醖鹹襯蓋(鏇製淵廠淵蓋膚製鬱壓) = 願鑰鏇憲齋淵鹹遞夢鹹願糧製築製遞衊築積廠 (廠鬱簾簾遞簾製範願鑰 ) 更多	积极	2023-04-23