预约演示

更新于：2026-04-03

Epratuzumab

依帕珠单抗

更新于：2026-04-03

概要

基本信息

药物类型

单克隆抗体

别名

Epratucyn、Epratuzumab (USAN/INN)、Humanised monoclonal antibody LL2

+ [11]

靶点

CD22

作用方式

调节剂

作用机制

CD22调节剂(CD22调节剂)、ADCC(抗体依赖的细胞毒作用)

治疗领域

肿瘤免疫系统疾病心血管疾病+ [2]

在研适应症

慢性淋巴细胞白血病淋巴浆细胞性淋巴瘤多发性骨髓瘤+ [1]

非在研适应症

CD20阳性滤泡性淋巴瘤CD22阳性急性淋巴细胞白血病弥漫性大B细胞淋巴瘤+ [7]

原研机构

Immunomedics, Inc.

在研机构

Immunomedics, Inc.

非在研机构

UCB Pharma GmbH

The Children's Oncology Group Foundation, Inc.

Alliance Foundation Trials LLC

+ [1]

权益机构

Amgen, Inc.

UCB SA

Immunomedics, Inc.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

Sequence Code 146718L

来源: *****

Sequence Code 9620786H

来源: *****

关联

项与依帕珠单抗相关的临床试验

NCT02306629

/ Completed临床1期

An Open-label, Parallel-group, Single-dose Escalation Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Pharmacodynamics of Subcutaneous Epratuzumab in Healthy Caucasian and Japanese Subjects

To assess how the absolute bioavailability, dose proportionality, pharmacokinetics, safety and tolerability of epratuzumab compared when given as a subcutaneous (sc) injection as to when given as an intravenous (iv) infusion in Caucasian and Japanese healthy volunteers.

开始日期2014-11-01

申办/合作机构

UCB Biopharma SRL

[+5]

NCT02167711

/ Completed临床2期IIT

Selective Internal Radiation Therapy With Yttrium-90 Resin Microspheres Followed by Gemcitabine Plus Cisplatin for Intra-hepatic Cholangiocarcinoma: A Phase II Study

The current standard treatment of inoperable intrahepatic cholangiocarcinoma (bile duct cancer in the liver) is chemotherapy, which is of limited efficacy. The use of selective internal radiotherapy treatment (SIRT-Y90) is proven efficacious in patients with intra-heptic tumor. Previous experience with SIRT is safe in patients with intrahepatic cholangiocarcinoma. This study aims to study the benefits of sequential administration of SIRT followed by standard chemotherapy for treatment of inoperable intrahepatic cholangiocarcinoma.

开始日期2014-09-17

申办/合作机构

香港中文大学

NCT01802814

/ Completed临床3期IIT

International Study for Treatment of Standard Risk Childhood Relapsed ALL 2010 A Randomized Phase III Study Conducted by the Resistant Disease Committee of the International BFM Study Group

The main goal of this study is to improve the outcome of children and adolescents with standard risk (SR) first relapsed acute lymphoblastic leukemia. Furthermore, goal is to set up a large international study group platform allowing for optimization of standard treatment strategies and integration of new agents.

开始日期2014-05-01

申办/合作机构

Charité - Universitätsmedizin Berlin

[+11]

100 项与依帕珠单抗相关的临床结果

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100 项与依帕珠单抗相关的转化医学

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100 项与依帕珠单抗相关的专利（医药）

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173

项与依帕珠单抗相关的文献（医药）

2026-02-01·AUTOIMMUNITY REVIEWS

Risk of infection for different B-cell targeting agents in treating systemic lupus erythematosus: A systematic review and network meta-analysis

Review

作者: Lin, Yuxiang ; Yu, Zhibin

OBJECTIVES:

This study aimed to assess the risk of infections in the treatment of systemic lupus erythematosus (SLE) with various B-cell targeting agents.

METHODS:

We systematically searched PubMed, Web of Science, Cochrane Library, and Embase for randomized controlled trials (RCTs) of B-cell targeting agents for SLE as of March 1, 2025. The risk of bias was assessed using Cochrane and NIH tools. The main outcomes were total and serious infections. We performed traditional (TMA) and network meta-analyses (NMA). The risk ratios (RRs) with 95% confidence intervals (CIs) or credible intervals (CrIs) were calculated.

RESULTS:

A total of 26 studies with 16,338 patients were included, involving 12 B-cell targeting agents. Overall, B-cell targeting therapy did not significantly increase the risk of infections. Nonetheless, obinutuzumab was associated with a greater risk of infections in patients with lupus nephritis compared to placebo (RR [95% CrI] = 1.18 [1.03, 1.37]) and rituximab (RR [95% CrI] = 1.25 [1.04, 1.53]). It was also associated with an elevated risk of infections in the combined population compared to placebo (RR [95% CrI] = 1.18 [1.03, 1.36]), rituximab (RR [95% CrI] = 1.22 [1.04, 1.43]), and epratuzumab (RR [95% CrI] = 1.24 [1.06, 1.45]). BAFF/APRIL-targeting agents showed a higher risk of infections than anti-CD22 agents (only epratuzumab) (RR [95% CrI] = 1.16 [1.01, 1.34]). Low-dose therapy also showed a notably increased risk compared to placebo (RR [95% CrI] = 1.05 [1.00, 1.10]). No significant increase in the risk of serious infections was found.

CONCLUSIONS:

Specific B-cell targeting therapies may modestly increase the risk of total infections.

2024-07-01·PEDIATRIC DRUGS

Inotuzumab Ozogamicin: First Pediatric Approval

Review

作者: Dhillon, Sohita

Inotuzumab ozogamicin (BESPONSA™) is a CD22-targeted monoclonal antibody drug conjugate (ADC) developed by Pfizer for the treatment of CD22-postive B-cell precursor acute lymphoblastic leukaemia (ALL). Inotuzumab ozogamicin comprises a humanized IgG4 anti-CD22 monoclonal antibody covalently linked to the potent DNA-binding cytotoxic agent N-acetyl-gamma-calicheamicin dimethylhydrazide (CalichDMH) via a linker. Inotuzumab ozogamicin binds to CD22-expressing tumour cells, facilitating the delivery of conjugated CalichDMH, which after intracellular activation induces double strand DNA breaks, ultimately leading to cell cycle arrest and apoptotic cell death. Inotuzumab ozogamicin is approved in the USA, Europe and several countries worldwide for the treatment of relapsed or refractory CD22-positive B-cell precursor ALL in adults. On 6 March 2024, inotuzumab ozogamicin received its first pediatric approval in the USA for this indication in patients aged ≥ 1 years. Inotuzumab ozogamicin has since been approved in Japan in March 2024 for the same indication in pediatric patients. This article summarizes the milestones in the development of inotuzumab ozogamicin leading to this first approval for the treatment of relapsed or refractory CD22-positive B-cell precursor ALL in pediatric patients.

2024-02-01·CPT: pharmacometrics & systems pharmacology

Model‐based meta‐analysis using latent variable modeling to set benchmarks for new treatments of systemic lupus erythematosus

Article

作者: Roy, Sanjeev ; Mateo, Cristina Vazquez ; Klopp‐Schulze, Lena ; Goteti, Kosalaram ; Venkatakrishnan, Karthik ; Gillespie, William R. ; French, Jonathan ; Garcia, Ramon ; Guenther, Oliver ; Li, Ying ; Benincosa, Lisa

Abstract:

Several investigational agents are under evaluation in systemic lupus erythematosus (SLE) clinical trials but quantitative frameworks to enable comparison of their efficacy to reference benchmark treatments are lacking. To benchmark SLE treatment effects and identify clinically important covariates, we developed a model‐based meta‐analysis (MBMA) within a latent variable model framework for efficacy end points and SLE composite end point scores (BILAG‐based Composite Lupus Assessment and Systemic Lupus Erythematosus Responder Index) using aggregate‐level data on approved and investigational therapeutics. SLE trials were searched using PubMed and www.clinicaltrials.gov for treatment name, SLE and clinical trial as search criteria that resulted in four data structures: (1) study and investigational agent, (2) dose and regimen, (3) baseline descriptors, and (4) outcomes. The final dataset consisted of 25 studies and 81 treatment arms evaluating 16 different agents. A previously developed (K Goteti et al. 2022) SLE latent variable model of data from placebo arms (placebo + standard of care treatments) was used to describe aggregate SLE end points over time for the various SLE placebo and treatment arms in a Bayesian MBMA framework. Continuous dose‐effect relationships using a maximum effect model were included for anifrolumab, belimumab, CC‐220 (iberdomide), epratuzumab, lulizumab pegol, and sifalimumab, whereas the remaining treatments were modeled as discrete dose effects. The final MBMA model was then used to benchmark these compounds with respect to the maximal efficacy on the latent variable compared to the placebo. This MBMA illustrates the application of latent variable models in understanding the trajectories of composite end points in chronic diseases and should enable model‐informed development of new investigational agents in SLE.

项与依帕珠单抗相关的新闻（医药）

2026-03-16

·百度百家

颠覆性突破！国研“三明治”疗法让B-ALL患者2年生存率飙至97%，CD22靶点再立新功

近年来，随着CAR-T细胞疗法在B细胞恶性肿瘤治疗中取得突破性进展，如何进一步提高疗效、克服抗原逃逸及T细胞耗竭等问题，已成为领域内研究的热点。CD22作为B细胞特异性表面分子，长期以来被认为是免疫治疗的理想靶点之一，其在成熟B细胞及多数B细胞淋巴瘤中的限制性表达，使其在抗体药物和CAR-T疗法中均展现出广阔的应用前景。2025年发表的多项研究进一步拓展了CD22靶向治疗的策略：一方面，CD19xCD22双顺反子CAR-T通过差异化信号整合，在增强抗肿瘤活性的同时减轻T细胞耗竭，展现出优于传统单靶点设计的潜力；另一方面，国内首创的“三明治”疗法（CD22/CD19 CAR-T联合自体干细胞移植）在新诊断B-ALL患者中实现了高达97%的2年总生存率，标志着CD22靶向治疗从实验室走向临床的又一次重要跃升。本文将从CD22的结构、信号通路及其在疾病中的作用出发，结合最新临床进展，系统梳理CD22作为治疗靶点的理论基础与应用前景。 1. CD22是什么？ 2. CD22的结构 3. CD22的配体与信号通路 3.1 CD22的配体 3.2 CD22信号通路 4. CD22与疾病 4.1 CD22与自身免疫疾病 4.2 CD22与血液癌症 5. CD22相关药物研究进展 6. CD22相关研究工具 1. CD22是什么？ CD22，又被称为Siglec-2，普遍存在于正常B细胞和B细胞恶性肿瘤中。CD22主要表达于成熟B细胞，是具有调控B细胞激活作用的细胞表面粘附分子，有助于B细胞对抗原反应敏感性的控制[1][2][3]。Tedder TF团队进一步证明了CD22表达在B细胞中具有特异性，并且在小鼠和人类中都受到发育调控[4]。如Figure 1所示，CD22可在原B细胞和前B细胞中表达，并逐渐转移到细胞表面，但是表达水平低；在IgM+和IgD+的成熟B细胞高表达，在滤泡性B细胞、套细胞、边缘区B细胞也高表达，但最终在CD27+记忆B细胞，尤其是浆细胞中，表达下调[5]。此外，最近的研究发现，在小鼠肠酸性粒细胞也观察到了CD22表达，这是一种新型的表达模式，表明CD22可能具有嗜酸性粒细胞调节功能[6]。 Figure 1. CD22 protein expression during B-cell development and activation. 2. CD22的结构如Figure 2所示，人类CD22基因位于19号染色体长臂(19q13.1)，至少有15个外显子，其中外显子4-10编码单链Ig域，外显子11-15编码跨膜结构域和胞内结构域。 Figure 2. CD22 chromosomal location and organization. CD22蛋白是I型跨膜蛋白，分子量为140 kDa，是唾液酸结合的免疫球蛋白样凝集素家族的重要成员。CD22的胞外域包含七个Ig域（Figure 3），最远端的V-set Ig域在结合α2,6唾液酸(α2,6sia)配体中起主要作用，相连的C2-set Ig域的功能可能是允许V-set Ig域正确折叠[7][8]。CD22的胞内域包括免疫受体酪氨酸抑制基序(ITIM)和免疫受体酪氨酸活化基序(ITAM)[9]。Ig样结构域1和2包含配体结合区；当六个保守的酪氨酸残基中的一个或多个被磷酸化时，各种效应分子被募集到胞质域。CD22α和CD22β是CD22的两种亚型，其胞外域分别有5个和7个Ig域，这两种cDNA亚型来源于同一基因的不同拼接。 Figure 3. CD22 structure. 3. CD22的配体与信号通路 3.1 CD22的配体 CD22可以与含唾液酸的细胞相互作用，包括T细胞、B细胞、中性粒细胞、单核细胞和红细胞[10][11]。其中能与CD22胞外配体结合域相互作用的B细胞表面唾液酸配体为顺式配体，其他细胞表面配体则为反式配体。CD22通过顺式作用与B细胞表面的配体结合，通过反式作用与其他细胞表面配体、可溶性糖蛋白或细胞连接的抗原结合[12]。顺式配体是CD22的主要结合配体，也是CD22活性的重要调节剂。CD22作为B细胞受体(BCR)的一个共受体，通过抗原引起CD22与BCR交联，触发CD22磷酸化，使下游信号蛋白去磷酸化和失活，从而抑制BCR信号传导，是抑制BCR的必需因子。CD22的反式作用可能介导细胞间交联、控制B细胞黏附和迁移，并对T细胞信号传导有重要意义。大多数B细胞表面的CD22呈遮蔽态，限制它们与反式配体的作用，除非细胞经过唾液酸酶或高碘酸盐预处理，才能结合外源性唾液酸。非遮蔽态CD22可能促进其与反式配体或顺式配体的特殊亚基(可能包括BCR)作用。 3.2 BCR调节机制及下游信号通路 CD22对B细胞信号传导的调节能力由CD22与BCR的远近决定，同时也受细胞外相互作用的控制。CD22是BCR的一个共受体，通过抗原或抗Ig引起CD22与BCR交联。CD22与BCR交联后会集中到脂筏上，然后Lyn会磷酸化CD22的酪氨酸残基[13][14]。磷酸化后，这些酪氨酸残基会变成下游信号分子SH2结构域的结合位点，这些分子会进一步激活其他信号传导分子（Figure 4）。例如Src同源性磷酸酶1（SHP-1）蛋白，主要作用是去磷酸化BCR，从而下调BCR信号并调节Ca2+信号转导[15]。 SHP-1的作用对象包括CD19和SLP65/B细胞接头蛋白（BLNK）[16]。其中SLP65/BLNK可形成一个支架并关联多个信号分子，包括Vav-1、Bruton酪氨酸激酶（Btk）和磷脂酶Cγ2（PLCγ2）。PLCγ2将磷脂酰肌醇4,5-双磷酸酯（PtdIns（4,5）P2）转化为1,4,5-三磷酸肌醇（Ins（1,4,5）P3）和二酰基甘油（DAG）。Ins（1,4,5）P3可通过多种途径促进Ca2+从细胞内存储的释放，包括Ca2+释放激活通道（CRAC）活化、核因子κB（NF-κB）激活，T细胞和因子（NFAT）活化及胞外信号调节激酶信号通路。 Figure 4. Intracellular signaling pathways of CD22 4. CD22与疾病在第三部分中已经提到，CD22 分子对BCR复合物识别抗原产生的信号起抑制作用[16]。该抑制作用在CD22缺陷小鼠的研究实验中得到了进一步验证[17]。CD22缺陷小鼠的B细胞均表现出轻微活化状态，high IgD、low IgM的成熟B细胞比例增高，B细胞表面IgM (sIgM)水平降低，IgM的分泌增加，MHC II类分子表达量增加，B细胞激活的阈值下调[18]。作为限制B细胞的抗原，CD22为治疗自身免疫疾病和血液癌症中的B细胞失调提供了有效靶点。 4.1 CD22与自身免疫性疾病 CD22通过与BCR交联，抑制B细胞对自身抗原的反应，阻止自身反应性B细胞激活，从而抑制自身免疫性疾病的发生。CD22表达或功能受损在自身免疫性疾病的发病机制中起作用，如系统性红斑狼疮(SLE)、类风湿性关节炎(RA)等[19][20]。 SLE是一种常见的累及多脏器的慢性系统性自身免疫性疾病，其主要特征是多克隆B细胞异常活化、自身抗体产生、免疫复合物沉积，引起多脏器损伤。CD22缺陷小鼠的B细胞对受体信号的反应过度，BCR结合引起的Ca2+内流增加，使血清IgG抗dsDNA抗体滴度增加，这些抗体是多克隆起源的，存在不良变异和高亲和力。 4.2 CD22与血液癌症在第一部分中，我们已经提到，CD22仅在成熟B细胞中表达。在大多数情况下，正常B细胞向肿瘤细胞转化过程中CD22 分子依然表达。相关数据显示，约60-80%的B细胞系淋巴瘤及白血病细胞表达CD22分子。目前除了化学疗法、放射疗法和裸mAb疗法之外，放射免疫疗法正在成为非霍奇金淋巴瘤患者的第四种治疗方法。放射性标记的CD22 mAb在B细胞淋巴瘤诊断和分期中敏感度很高。131I或90Y标记的CD22 mAb（LL2，埃普拉单抗）与CD22细胞外第三个Ig结构域结合可以完全缓解由裸CD22 mAb（LL2）在体外介导的抗体和补体依赖性细胞毒性[21][22]。 5. CD22相关药物研究进展 CD22分子是B细胞表面抑制性辅助受体之一，它与B细胞的发展、分化和功能有着密切的关系。CD22限制性地表达于成熟B细胞和大多数B淋巴瘤细胞表面。以CD22为靶点，进行肿瘤免疫治疗已经成为免疫研究热点之一。目前，关于CD22分子的免疫靶向治疗，除了治疗性抗体外，还有CAR-T细胞疗法。截止到2019年11月，虽然CD22相关抗体药物已批准上市的只有两种，但关于CD22 CAR-T细胞治疗和抗体药物的临床研究有近108项。FDA已批准上市的CD22相关药物如下表所示：药物作用机制药物类型在研适应症（疾病名）在研机构最高研发阶段帕西妥莫单抗 CD22抑制剂抗体偶联毒素毛细胞白血病 Innate Pharma SA 批准上市奥加伊妥珠单抗 CD22抑制剂 | DNA抑制剂 ADC 费城染色体阳性成人前体急性淋巴细胞白血病等 Pfizer Inc. | Pfizer Pharmaceuticals Korea Ltd. | Pfizer Europe MA EEIG | Wyeth Pharmaceuticals LLC | Pfizer (Perth) Pty Ltd. 批准上市 AUTO-3 CD19调节剂 | CD22抑制剂自体CAR-T 肿瘤 | 复发性中枢神经系统淋巴瘤 | CD19阳性急性淋巴细胞白血病 Autolus Ltd. | University College London 临床2/3期依帕珠单抗 CD22调节剂 | ADCC 单克隆抗体慢性淋巴细胞白血病 | 淋巴浆细胞性淋巴瘤 | 多发性骨髓瘤 | 巨球蛋白血症 Immunomedics, Inc. 临床2期重组人CD22单克隆抗体(Sinomab Bioscience/Lonn Ryonn Pharma) CD22抑制剂单克隆抗体非霍奇金淋巴瘤 | 系统性红斑狼疮 | 阿尔茨海默等中抗生物制药（海口）有限公司 | 中國抗體製藥有限公司临床2期 Anti CD22 CAR-T cell therapy (YaKe Biotech) CD22抑制剂 CAR-T 难治性 B 细胞急性淋巴细胞白血病 | 急性淋巴细胞白血病等上海雅科生物科技有限公司 | 北京高博博仁医院有限公司临床2期 CD19CD22 CAR-T Therapy(The First Affiliated Hospital of Soochow University) CD19调节剂 | CD22调节剂 | 免疫细胞毒性 | T淋巴细胞替代物 CAR-T CD19阳性B细胞急性淋巴细胞白血病等苏州大学附属第一医院临床2期 CD19 and CD22 CAR-T(Yake Biotechnology) CD19调节剂 | CD22调节剂 | 免疫细胞毒性 | T淋巴细胞替代物自体CAR-T 费城染色体阳性急性淋巴细胞白血病 | 前体B细胞成淋巴细胞白血病淋巴瘤等上海雅科生物科技有限公司临床2期 tanCART-19/22 cells CD19抑制剂 | CD22抑制剂 CAR-T 伴11q畸变的伯基特样淋巴瘤 | CD19阳性弥漫性大B细胞淋巴瘤等中国人民解放军总医院临床2期 6. CD22相关研究工具 ● CD22蛋白 Recombinant Human B-cell receptor CD22(CD22),partial (Active) (Code: CSB-MP004900HU) High Purity Validated by SDS-PAGE (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel. Excellent Bioactivity Validated by Functional ELISA Immobilized CD22 at 2 μg/ml can bind Anti-CD22 rabbit monoclonal antibody, the EC50 of human CD22 protein is 4.034-4.800 ng/ml. References [1] Pezzutto A, Rabinovitch PS, et al. Role of the CD22 human B cell antigen in B cell triggering by anti-immunoglobulin [J]. J Immunol. 1988, 140:1791–1795. [2] Wilson GL, Fox CH, et al. cDNA cloning of the B cellmembrane protein CD22: amediator of B-B cell interactions [J]. J ExpMed. 1991, 173:137–146. [3] Thomas Dorner, Anthony Shock, et al. CD22 and Autoimmune Disease [J]. International Reviews of Immunology. 2012, 31:363–378. [4] Tedder TF, Poe JC, et al. CD22: a multifunctional receptor that regulates B lymphocyte survival and signal transduction [J]. Adv Immunol. 2005, 88:1-50. [5] Daridon C, Blassfeld D, et al. Epratuzumab targeting of CD22 affects adhesion molecule expression andmigration of B-cells in systemic lupus erythematosus [J]. Arthritis ResTher. 2010, 12:R204. [6] Wen T, Mingler MK, et al. The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia [J]. J Immunol. 2012, 188:1075–1082. [7] Engel P, Wagner N, et al. Identification of the ligand-binding domains of CD22, a member of the immunoglobulin superfamily that uniquely binds a sialic acid-dependent ligand [J]. J ExpMed. 1995, 181:1581–1586. [8] Nath D, van derMerwe PA, et al. Theamino-terminal immunoglobulin like domain of sialoadhesin contains the sialic acid binding site: comparison with CD22 [J]. J Biol Chem. 1995, 270:26184–26191. [9] Wilson GL, Fox CH, et al. cDNA cloning of the B cell membrane protein CD22: a mediator of B-B cell interactions [J]. J ExpMed. 1991, 173:137–146. [10] Engel P, Nojima Y, et al. The same epitope on cD22 of B lymphocytes mediates the adhesion of erythmcytes, T and B lymphocytes, neutrophils, and monocytes [J]. J Immunol. 1993, 150(11):4719-4732. [11] Ramya TN, Weerapana E, et al. In situ trans ligands of CD22 identi6ed by glycan-protein photocross-linking-enabled proteomics [J]．Mol Cell Pmteomics. 2010, 9(6):1339-1351. [12] Smith KGC, Tarlinton DM, et al. Inhibition of the B cell by CD22: a requirement for Lyn [J]. J ExpMed. 1998, 187:807-811. [13] Xu Y, Harder KW, et al. Lyn tyrosine kinase: accentuating the positive and the negative. Immunity [J]. 2005, 22:9–18. [14] Doody GM, Justement LB, et al. A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP [J]. Science. 1995, 269:242–244. [15] Gerlach J, Ghosh S, et al. B cell defects in SLP65/BLNK-deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signaling [J]. Eur J Immunol. 2003, 33:3418–3426. [16] June Ereño-Orbea, Taylor Sicard, et al. Molecular basis of human CD22 function and therapeutic targeting [J]. Nature Communications. 2017, 8(764). [17]Samardzie T, Marinkovic D, et al．Reduction of marginal zone B cells in CD22-deficient mice [J]. Eur J Immunol. 2002, 32(2):561-567. [18] Tooze RM, Doody GM, et al. Counterregulation by the coreceptom CDl9 and CD22 of MAP kinase activation by membrane immunoglobulin [J]. Immunity. 1997, 7(1):59-67. [19] O Keefe TL, Williams GT, et al. Hyperresponsive B cells in CD22-de6cient mice [J]. Science. 1996, 274(5288):798-801. [20] Nakiri Y, Minowa K, et al. E1pression of CD22 on peripheral B cells in patients with rheumatoid arthritis: relation to CD5-positive B cells [J]. Clin Rheumatol. 2007, 26(10):1721-1723. [21] Thomas F. Tedder, Jonathan C. Poe, et al. CD22: A Multifunctional Receptor That Regulates B Lymphocyte Survival and Signal Transduction [J]. Advances in immunology. 2005, 88:1-50. [22] Carnahan, J., Wang, P., et al. Epratuzumab, a humanized monoclonal antibody targeting CD22: Characterization of in vitro properties [J]. Clin. Cancer Res. 2003, 9:3982S–3990S.

细胞疗法免疫疗法

2026-03-04

·知乎专栏

治疗系统性红斑狼疮的新希望——生物制剂

生物制剂是近年来用于治疗系统性红斑狼疮众多药物中的“后起之秀”。这是一类新型的基因工程类药物，如单克隆抗体或天然抑制分子(如白细胞介素-1、6)的重组产物。相对于糖皮质激素、免疫抑制剂等“老药”，生物制剂常常能够“定向”干预参与机体免疫或炎症反应，降低了伤及正常组织的几率，且提高了药物作用效果。与一些传统药物如环磷酰胺、吗替麦考酚酯相比，起效迅速是生物制剂的优势。目前全球批准用于治疗系统性红斑狼疮的生物制剂有利妥昔单抗（Rituximab）和贝利单抗（Belimumab）两种。在我国大陆获批上市应用于临床的药物仅利妥昔单抗一种。下面我们就来详细了解一下这类新药。利妥昔单抗（Rituximab）系统性红斑狼疮患者的 B 细胞异常活化，利妥昔单抗能够定向地“针对”这些 B 细胞、使其数量减少、功能下降，这是利妥昔单抗治疗系统性红斑狼疮的基础。用于治疗传统糖皮质激素或免疫抑制剂治疗无效的患者，如合并狼疮肾炎、狼疮难治性血小板减少、神经精神狼疮等情况的患者，治疗效果较好。使用相对安全：最常见的副作用是输注反应。患者会表现为寒战、心悸、胸闷、皮疹等。通常在输注前预防性使用抗组胺药物、糖皮质激素等可以避免。但是如若在输注过程中出现上述不适，需及时通知医护人员，根据严重度，医生会考虑尝试减缓输注速度甚至停用。感染是第二位常见的副作用，但多为轻度感染，重症和其他机会性致病菌（如真菌）感染并不常见。如若发现感染“迹象”，如呼吸道部感染发生咽痛、咳嗽、咯痰、发热等，泌尿道感染发生尿频、尿急、尿痛等情况，请及时就诊。费用昂贵。贝利单抗（Belimumab）B 淋巴细胞刺激蛋白（BlyS/BAFF）在 B 细胞存活和成熟过程中有重要作用，贝利单抗就是通过抑制这个蛋白，从而达到抑制 B 细胞活化的目的，这是贝利单抗治疗系统性红斑狼疮的理论基础。在国外，贝利单抗主要用于治疗没有肾脏和神经系统损害的红斑狼疮患者。它能够有效改善患者的关节炎、皮肤黏膜病变（如脱发、黏膜溃疡及蝶形红斑等）、皮肤血管炎症状，还能改善一些免疫学指标水平，如低补体、抗双链 DNA 水平升高等指标，从而改善疾病活化程度。各种类型的感染仍是贝利单抗使用最常见的不良反应。其他正在“赶来”的生物制剂除上述两种生物制剂外，还有其他目前仍处在临床试验阶段的用于治疗系统性红斑狼疮的生物制剂，可能是系统性红斑狼疮治疗的“明日之星”。Epratuzumab不仅降低系统性红斑狼疮患者整体疾病活动度，而且不良反应相对小，和接受安慰剂治疗患者相比，接受 Epratuzumab 患者感染风险并未显著增加。Blisibimod一项 II 期临床研究表明，Blisibimod 可以有三大作用：稳定系统性红斑狼疮疾病的病情；减少糖皮质激素用量；降低尿蛋白水平。而且与利妥昔单抗和贝利单抗均需输液不同，Blisibimod为皮下注射，使用更为方便。生物制剂的出现为难治性系统性红斑狼疮治疗提供了新的选择，随着生物制剂在临床中的普及，越来越多的患者可望从中获益。共同作者：北京医院风湿免疫科陈哲医生本文作者：北京医院副主任医师陈颖娟本文审阅：北京医院主任医师黄慈波

临床研究上市批准

2026-03-04

·allsci.com

UCB bags Antengene’s CD19/CD3 bispecific TCE for autoimmune diseases for up to USD 1.3b

Hong Kong-headquartered Antengene Corporation and Brussels-based UCB (Euronext Brussels) announced a global license agreement granting UCB worldwide exclusive rights to develop, manufacture, and commercialize ATG-201, a CD19/CD3 bispecific T-cell engager antibody targeting B cell-related autoimmune diseases. For UCB, the deal represents a return to B cell-targeting strategies in the immunology space. UCB gains access to the manufacturing technology related to ATG-201, while Antengene will lead on IND filings for the molecule and initiation of first-in-human Phase I studies in China and Australia before transferring further clinical development to UCB. Antengene will receive USD 60 million upfront and USD 20 million in near-term milestone payments, totaling USD 80 million in upfront and near-term consideration. The company is eligible for over USD 1.1 billion in success-based development, regulatory, and sales milestones, along with tiered royalties on future net sales. The deal is structured as a full global out-license, with Antengene retaining no long-term territorial commercialization rights. Deal context ATG-201 is a bispecific antibody built on Antengene’s proprietary AnTenGager platform, which uses a “2+1” format — two CD19 binding arms and one CD3 binding arm — combined with steric hindrance masking technology and a proprietary fast-on-fast-off CD3 binder. The molecule is designed to redirect T cells to eliminate CD19-expressing B cells while reducing the risk of cytokine release syndrome. Antengene plans to submit clinical trial applications for ATG-201 in China and Australia in Q1 2026. The asset is pre-Phase I, with no clinical trial registry entries publicly available at the time of announcement. For UCB, the deal adds a B cell autoimmune therapy modality to an immunology pipeline historically built on monoclonal antibodies and other biologics. UCB previously pursued CD22-targeted B cell depletion through an epratuzumab collaboration with Immunomedics, structured in 2009 with approximately USD 38 million upfront and later restructured in 2011; that program was ultimately discontinued. The ATG-201 agreement represents a return to B cell-targeting strategies, this time via a T-cell engager format. No prior deals between Antengene and UCB were identified; this is the first transaction between the two companies. For Antengene, the transaction represents a shift from its historical pattern of in-licensing Western assets for Asia-Pacific development — such as its selinexor license from Karyopharm Therapeutics — to out-licensing a proprietary, platform-derived candidate to a global pharma company. Nine additional disclosed products remain in the AnTenGager pipeline. The Antengene transaction comes amid rising industry investment in T-cell engager therapies targeting B-cell biology in autoimmune diseases. In January 2025, Merck acquired global ex-China rights to Curon Biopharmaceutical’s CD19×CD3 bispecific antibody CN201 in a deal worth up to USD 1.3 billion, including USD 700 million upfront. Candid Therapeutics is another TCE specialist focused on autoimmune programs, and recently merged with Rallybio gaining USD 505 million in new financing, with programs targeting BCMA, CD20, and CD19/CD20 combinations. The modality also has precedent in oncology through Amgen’s CD19/CD3 bispecific blinatumomab (Blincyto), which is currently being evaluated in a Phase II autoimmune disease study (NCT06570798) in systemic lupus erythematosus and rheumatoid arthritis. Meanwhile, CD19 CAR-T therapies for autoimmune disease include Kyverna Therapeutics’ KYV-101, currently Phase 2 for lupus nephritis. The UCB license agreement positions the company within this competitive set, though ATG-201’s differentiated platform design — incorporating conditional T-cell activation via steric masking — may address tolerability concerns that have limited earlier CD19/CD3 bispecific T-cell engager approaches. ATG-201 remains at an early development stage, and clinical data will be required to confirm whether the platform’s design translates into a differentiated safety and efficacy profile relative to both CAR-T and other TCE modalities targeting autoimmune diseases indications. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

引进/卖出临床1期临床2期免疫疗法

100 项与依帕珠单抗相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D04036	依帕珠单抗	-	DB04958

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适应症	最高研发状态	国家/地区	公司	日期
系统性红斑狼疮	临床3期	美国	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	比利时	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	巴西	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	加拿大	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	捷克	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	法国	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	德国	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	意大利	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	荷兰	UCB Pharma GmbH	2005-05-01
系统性红斑狼疮	临床3期	西班牙	UCB Pharma GmbH	2005-05-01

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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


NCT00553501 \| NCT01145495 \| NCT00117975 (CALGB, Pubmed \| Cancer Med) 人工标引	临床2期	滤泡性淋巴瘤一线	174	rituximab+R-galiximab+R-epratuzumab+R-lenalidomide (early POD)	簾製窪衊蓋積積衊遞窪(蓋齋顧糧遞繭膚觸選蓋) = 壓觸顧廠簾餘餘積壓壓壓構蓋鑰壓鬱襯衊鏇鏇 (壓鏇簾選願鬱淵獵蓋蓋 ) 更多	积极	2019-01-01
				rituximab+R-galiximab+R-epratuzumab+R-lenalidomide (nonearly POD)	簾製窪衊蓋積積衊遞窪(蓋齋顧糧遞繭膚觸選蓋) = 糧鑰築獵鑰淵願衊壓觸壓構蓋鑰壓鬱襯衊鏇鏇 (壓鏇簾選願鬱淵獵蓋蓋 ) 更多
NCT01262365 (EMBODY 1, EMBODY 2 \| EMBODY1, CTgov)	临床3期	系统性红斑狼疮	793	Placebo (Placebo (Weekly Infusion))	壓選繭膚糧積襯醖構製(蓋鏇製築蓋膚齋鬱壓選) = 襯鏇壓構獵鹽簾範網鏇製繭選蓋廠鬱鹽衊襯構 (醖鬱艱顧膚觸齋鏇鏇鹹, 襯範鏇獵廠窪膚衊構衊 ~ 壓鬱鏇淵壓繭選夢廠範) 更多	-	2018-06-29
				Placebo+Epratuzumab (Epratuzumab 1200 mg Every Other Week)	壓選繭膚糧積襯醖構製(蓋鏇製築蓋膚齋鬱壓選) = 獵顧憲簾選構範淵鏇壓製繭選蓋廠鬱鹽衊襯構 (醖鬱艱顧膚觸齋鏇鏇鹹, 廠觸膚網窪選鏇糧廠廠 ~ 齋構範觸築築蓋壓遞簾) 更多
NCT01261793 (EMBODY2 \| EMBODY 1, EMBODY 2, CTgov)	临床3期	系统性红斑狼疮	791	Placebo (Placebo Weekly (FAS))	淵壓網襯範夢淵窪鏇鬱 = 製醖壓齋顧壓鑰簾遞鬱淵觸願鑰艱觸齋膚顧鏇 (製齋壓醖選願鑰範鬱製, 夢鏇獵鹹鬱糧蓋窪願顧 ~ 醖製觸憲構蓋齋鏇範鏇) 更多	-	2018-06-29
				Epratuzumab (Epratuzumab 1200 mg Every Other Week (FAS))	淵壓網襯範夢淵窪鏇鬱 = 襯憲醖艱糧繭獵壓願蓋淵觸願鑰艱觸齋膚顧鏇 (製齋壓醖選願鑰範鬱製, 網繭淵窪築鑰鹹鬱艱願 ~ 願鏇餘蓋獵鹽夢鑰衊繭) 更多
NCT00660881 (SL0008, Pubmed \| Arthritis Care Res (Hoboken)) 人工标引	临床2期	系统性红斑狼疮	113	SoC+Epratuzumab	鹽壓鑰淵醖鑰築蓋鬱壓(鬱獵膚鑰鬱願簾齋鏇膚) = 淵鏇襯願艱憲顧顧衊憲顧繭顧壓齋願窪窪廠糧 (廠壓顧構憲廠獵簾襯壓 ) 更多	积极	2016-04-01
NCT01449071 (Pubmed \| Isr Med Assoc J \| Mod Rheumatol) 人工标引	临床1/2期	系统性红斑狼疮	19	epratuzumab	積膚醖積網遞窪艱網顧(鹹鏇膚蓋遞顧衊鬱遞壓) = 繭醖憲鹽醖繭範夢簾鏇壓築製淵餘廠網夢膚壓 (顧醖鑰襯蓋鏇鏇簾鹽壓 ) 更多	积极	2016-01-01
				Placebo	醖顧糧衊鏇糧選餘鹽憲(鑰壓餘窪觸範顧壓夢觸) = 鹹餘窪壓憲製網鹽夢鹽蓋鹹鑰繭糧廠願鹽襯餘 (製衊齋膚繭範膚願鹹簾 )
NCT00624351 (EMBLEM™, EULAR2015)	临床2期	系统性红斑狼疮 CD22 \| CD19 \| CD27 ... 更多	-	Epratuzumab	鏇顧鏇願憲鹽淵鏇範鏇(獵製繭網糧鏇鹹觸鹽蓋) = treatment at all dose levels induced a partial but dose-independent decrease in B cell counts 鹽顧齋膚淵鹽夢選窪廠 (壓餘築壓齋蓋夢構遞製 ) 更多	积极	2015-06-10
NCT00098839 (CTgov)	临床1/2期	复发性成人急性淋巴细胞白血病 \| CD22阳性急性淋巴细胞白血病 \| 复发性儿童急性淋巴细胞白血病	134	L-asparaginase+etoposide+pegaspargase+doxorubicin hydrochloride+methotrexate+Cytarabine+dexrazoxane hydrochloride+epratuzumab+cyclophosphamide+Leucovorin Calcium+prednisone+filgrastim+therapeutic hydrocortisone+vincristine sulfate (Reinduction Chemoimmunotherapy With Epratuzumab Once Weekly)	鬱糧窪鹽簾製構簾鏇選 = 鑰製蓋蓋艱遞鬱選齋餘憲願衊遞醖餘壓餘夢窪 (積壓繭鬱鏇糧醖淵餘選, 製製築築壓鹽範蓋衊夢 ~ 鬱繭鏇顧簾築製蓋構構) 更多	-	2015-03-26
				L-asparaginase+etoposide+pegaspargase+doxorubicin hydrochloride+methotrexate+Cytarabine+dexrazoxane hydrochloride+epratuzumab+cyclophosphamide+Leucovorin Calcium+prednisone+filgrastim+therapeutic hydrocortisone+vincristine sulfate (Reinduction Chemoimmunotherapy With Epratuzumab Twice Weekly)	鬱糧窪鹽簾製構簾鏇選 = 淵膚襯蓋衊廠鬱窪願艱憲願衊遞醖餘壓餘夢窪 (積壓繭鬱鏇糧醖淵餘選, 遞夢顧選鹹鑰鏇衊顧範 ~ 鑰鹽糧網獵願夢憲齋選) 更多
NCT00301821 (CTgov)	临床2期	弥漫性大B细胞淋巴瘤	107	epratuzumab+cyclophosphamide+prednisone+doxorubicin hydrochloride+vincristine sulfate+rituximab	窪襯鬱壓鹹顧糧鹽鹹膚 = 艱醖積積齋膚構獵餘築蓋顧襯廠簾壓選廠鏇襯 (憲觸築獵壓窪膚鏇夢襯, 選範餘構鏇願糧簾顧憲 ~ 鹽鬱鹽網淵艱艱願構獵) 更多	-	2015-03-24
NCT00553501 (CALGB 50701, CTgov)	临床2期	滤泡性淋巴瘤 \| CD20阳性滤泡性淋巴瘤	60	epratuzumab+rituximab	糧齋齋範廠遞壓鏇壓壓 = 築繭餘範網憲鏇廠壓獵獵窪糧夢鏇鬱積網範艱 (築廠築鬱蓋醖遞襯襯構, 鏇淵願獵繭醖鏇艱壓醖 ~ 鏇鹹選窪觸艱鹽衊鑰齋) 更多	-	2014-07-24
EULAR2014	临床3期	CD22	-	Epratuzumab	製顧夢築繭衊繭遞蓋構(蓋壓衊積襯網構簾鹽製) = 襯鹹繭範願鑰憲齋鑰壓窪膚廠鏇夢鏇遞憲膚壓 (遞襯觸鏇構繭顧鹹築齋 )	-	2014-06-11