CTLA-4/CD28信号通路

CTLA-4 作为免疫球蛋白超家族成员,是一种在免疫调节中扮演核心“刹车”角色的蛋白质受体,主要表达在活化的T细胞表面,包括CD4+辅助性T细胞和CD8+细胞毒性T细胞,并在调节性T细胞(Treg)上组成性高表达,是调节免疫抑制功能的关键靶点。
CD28 与CTLA-4均为T细胞表面的关键共刺激/共抑制受体,二者通过与抗原呈递细胞(APC)表面的B7家族配体(主要包括B7-1/CD80B7-2/CD86)相互作用,共同调控T细胞活化的“开关”,其分子机制与功能如下:
1. 活化信号通路:当T细胞通过T细胞受体(TCR)识别APC呈递的抗原肽-MHC复合物(第一信号)后,T细胞表面的CD28会与APC表面的B7分子(B7-1或B7-2)特异性结合,传递关键的共刺激信号(第二信号)。该信号可启动T细胞免疫应答,促进T细胞增殖、上调细胞因子分泌(如IL-2),并增强T细胞的效应功能(如CD8+T细胞的细胞毒性)。
2. 抑制信号通路:CTLA-4与B7分子的亲和力远高于CD28,可优先与B7结合,从而竞争性阻断CD28-B7介导的共刺激信号,切断T细胞活化的关键"助力",避免免疫过度激活导致机体损伤。
CTLA-4 / CD28信号通路
基于对功能的深刻理解,CTLA-4已成为药物研发的关键靶点,并在临床应用中展现出对应的双重策略。在自身免疫性疾病、肿瘤免疫治疗等关键治疗领域,已表现出显著临床价值。当前,从单抗到双抗等不同药物类型的前沿探索正推动该靶点疗法向更精准、高效的方向演进。

CTLA-4/CD28/B7-1/B7-2靶点应用

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应用领域 药物类型 药物名称(通用名/研发代码) 作用机制 研发公司/团队
肿瘤治疗 CTLA-4单克隆抗体 伊匹木单抗(Lpilimumab) 阻断CTLA-4与CD80/CD86结合,解除T细胞活化抑制,激活T细胞 百时美施贵宝(BMS)
替西木单抗(Tremelimumab) 全人源化IgG2单抗,特异性阻断CTLA-4通路,激活T细胞 阿斯利康
信达生物(IBI310) 国产CTLA-4单克隆抗体,机制与伊匹木单抗一致(阻断CTLA-4/CD80/CD86相互作用) 信达生物
PD-1/CTLA-4双特异性抗体 卡度尼利单抗(Cadonilimab) 同时靶向PD-1和CTLA-4双靶点,协同解除免疫检查点抑制,增强T细胞激活效率 康方生物/先声药业
艾帕洛利托沃瑞利单抗(QL1706) PD-1/CTLA-4双特异性抗体,通过分子设计优化毒性谱(降低传统联合用药的毒副作用) 齐鲁制药
CTLA-4/LAG-3双特异性抗体 MGD019 同时阻断CTLA-4和LAG-3两个免疫检查点,协同解除T细胞抑制并增强活化效应 MacroGenics
CTLA-4抗体前药 ProCTLA-4 前药形式的CTLA-4抗体,在肿瘤微环境中被基质金属蛋白酶(MMP)特异性切割后激活,实现肿瘤部位靶向性作用 傅阳心/王文彦团队
Evalstotug(BA3071) pH响应型CTLA-4抗体,仅在肿瘤酸性微环境中构象改变并激活,减少正常组织毒性 百济神州
CTLA-4/PD-L1/VEGF三特异性抗体 CS2009 同时阻断CTLA-4、PD-L1两个免疫检查点及VEGF血管生成因子,协同实现免疫激活与肿瘤血管抑制双重效应 基石药业
自身免疫性疾病治疗 CTLA-4-Ig融合蛋白 阿巴西普(Abatacept) CTLA-4胞外区与IgG1 Fc段融合,竞争性结合CD80/CD86,抑制T细胞过度活化 百时美施贵宝(BMS)
器官移植排斥预防 优化型CTLA-4-Ig融合蛋白 贝拉西普(Belatacept) 对CTLA-4胞外区进行改造,增强与CD80/CD86的亲和力,更高效抑制T细胞活化(减少移植排斥相关的免疫反应) 百时美施贵宝(BMS)
为满足 CTLA-4/CD28/B7-1/B7-2 靶点相关药物研发需求,ACROBiosystems百普赛斯开发了覆盖全研发环节的产品矩阵,核心包括:多种属(人、小鼠、非人灵长类)重组蛋白;B7-1: CTLA-4与B7-2: CTLA-4抑制剂筛选试剂盒;荧光标记、PG及GMP级CD28特异性抗体,用作细胞激活及分选;该产品矩阵覆盖CTLA-4/CD28/B7-1/B7-2通路相关研发场景,可满足抗体药及细胞治疗研发需求,同时ACROBiosystems百普赛斯也可以按需提供定制化产品与技术支持。

靶点蛋白产品特点

蛋白高纯度及天然结构经MALS/HPLC验证

严格的QC质检保证高批间一致性

蛋白高生物活性经ELISA/SPR/FACS等验证

产品列表

CTLA4
B7-1(CD80)
B7-2(CD86)
CD28

验证数据

MALS验证的CTLA-4二聚体结构
MALS验证的CTLA-4二聚体结构

Human CTLA-4, Fc Tag on SDS-PAGE under reducing (R) and non-reducing (NR) conditions. The gel was stained with Coomassie Blue. The purity of the protein is greater than 98%. The purity of Human CTLA-4, Fc Tag (Cat. No. CT4-H5255) is more than 90% and the molecular weight of this protein is around 82-100 kDa verified by SEC-MALS.

Report
B7-2与CTLA-4蛋白结合高活性经ELISA验证
B7-2与CTLA-4蛋白结合高活性经ELISA验证

Immobilized Human B7-2, His Tag (Cat. No. CD6-H5223) at 10 μg/mL (100 μL/well) can bind Human CTLA-4, Fc Tag (Cat. No. CT4-H5255) with a linear range of 2-78 ng/mL (QC tested).

Protocol

CD28与B7-1蛋白结合高活性经ELISA验证
CD28与B7-1蛋白结合高活性经ELISA验证

Immobilized Biotinylated Mouse CD28, His,Avitag (Cat. No. CD8-M82E3) at 1 μg/mL (100 μL/well) on Streptavidin (Cat. No. STN-N5116) precoated (0.5 μg/well) plate, can bind Human B7-1, Mouse IgG2a Fc Tag (Cat. No. B71-H52A4) with a linear range of 0.2-5 ng/mL (Routinely tested).

Protocol

CTLA-4与B7-1蛋白结合亲和力经BLI 验证
CTLA-4与B7-1蛋白结合亲和力经BLI 验证

Loaded Human CTLA-4, Fc Tag (Cat. No. CT4-H5255) on Protein A Biosensor, can bind Human B7-1, His Tag (Cat. No. B71-H5228) with an affinity constant of 0.52 μM as determined in BLI assay (ForteBio Octet Red96e) (Routinely tested).

Protocol

CTLA-4与B7-2蛋白结合亲和力经BLI 验证
CTLA-4与B7-2蛋白结合亲和力经BLI 验证

Loaded Human CTLA-4, Fc Tag (Cat. No. CT4-H5255) on Protein A Biosensor, can bind Human B7-2, His Tag (Cat. No. CD6-H5223) with an affinity constant of 1.9 μM as determined in BLI assay (ForteBio Octet Red96e) (Routinely tested).

Protocol

CTLA-4与双抗Cadonilimab的结合活性经ELISA验证
CTLA-4与双抗Cadonilimab的结合活性经ELISA验证

Immobilized Human CTLA-4, His Tag (Cat. No. CT4-H5229) at 5 μg/mL, add increasing concentrations of Cadonilimab (PD-1 x CTLA-4 bispecific antibody) and then add Biotinylated Human PD-1, Fc,Avitag (Cat. No. PD1-H82F1) at 0.2 μg/mL. (Routinely tested).

Protocol

CTLA-4与双抗Lpilimumab的结合活性经SPR验证
CTLA-4与双抗Lpilimumab的结合活性经SPR验证

Biotinylated Human CTLA-4, His,Avitag (Cat. No. CT4-H82E3) captured on Biotin CAP - Series S sensor Chip can bind Yervoy (Ipilimumab) with an affinity constant of 0.635 nM as determined in a SPR assay (Biacore T200) (Routinely tested).

Protocol

使用B7-1 [Biotinylated] : CTLA-4 抑制剂筛选试剂盒检测抗CTLA-4中和抗体对B7-1: CTLA-4结合的抑制效果
使用B7-1 [Biotinylated] : CTLA-4 抑制剂筛选试剂盒检测抗CTLA-4中和抗体对B7-1: CTLA-4结合的抑制效果

Serial dilutions of Anti-CTLA-4 Neutralizing antibody (Catalog # EP116-C04) (1:1 serial dilution, from 10 μg/mL to 0.078μg/mL) was added into CTLA-4: Biotinlated B7-1 binding reactions. The assay was performed according to the protocol described below. (QC tested).

CTLA-4×OX40双抗人血清 ELISA 定量检测
CTLA-4×OX40双抗人血清 ELISA 定量检测

Quantitative Analysis of CTLA-4 x OX40 Bispecific Antibody in Human Serum by Intact Assay.
Immobilized Human OX40 Protein, His Tag (MALS verified) (Cat. No. OX0-H5224) at 2 μg/mL, add increasing concentrations of CTLA-4 x OX40 bispecific antibody in 50% Human serum and then add Biotinylated Human CTLA-4, His, Avitag (Cat. No. CT4-H82E3) at 0.2 μg/mL. Detection was performed using HRP-conjugated streptavidin with sensitivity of 4 ng/mL (Intact assay, Routinely tested).

Protocol

CTLA-4临床药物信息

资源分享

  • 背景
  • CTLA-4/CD28/B7-1/B7-2靶点应用
  • 靶点蛋白产品特点
  • 产品列表
  • 验证数据
  • CTLA-4临床药物信息
  • 相关产品推荐
  • 资源分享