The PD-1/PD-L1 Axis and Co-signaling Networks: Orchestrating T Cell Responses in Cancer and Autoimmunity
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| 药物策略 | 策略类型 | 代表药物 / 方案 | 核心机制 / 目标 |
|---|---|---|---|
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靶向 PD-L1 ADC
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ADC
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1. PD-L1 ADC:复宏汉霖HLX43
2. PD-L1/αvβ6 整合素双靶点 ADC:康宁杰瑞 JSKN022
|
1. 以 PD-L1 为靶点,通过 ADC 的细胞毒性载荷实现靶向杀伤
2. 双重靶向 PD-L1 与 αvβ6 整合素,增强肿瘤靶向性与杀伤效果
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PD-1 Plus: 双抗
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免疫逃逸抑制 + 抗血管生成
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PD-1/VEGF 双抗:康方生物 依沃西单抗(AK112)
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同时阻断 PD-1 介导的免疫逃逸信号、抑制 VEGF 介导的肿瘤血管生成,改善肿瘤微环境,增强免疫治疗效果
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免疫逃逸抑制 + 免疫激动
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1. PD-1/IL-2 双抗:信达生物 IBI363
2. PD-L1/4-1BB 双抗:维立志博 LBL-024
|
在阻断免疫逃逸的同时,通过 IL-2/4-1BB 通路激活 T 细胞等免疫效应细胞,克服免疫治疗耐药
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多免疫逃逸抑制
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1. PD-1/TIGIT 双抗:阿斯利康 Rivegostomig
2. PD-1/CTLA-4 双抗:康方生物 卡度尼利单抗
|
同时阻断 PD-1 与 TIGIT/CTLA-4 等多个免疫抑制信号通路,强化对免疫逃逸的抑制作用
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PD-1/PD-L1 抑制剂与 ADC 药物联用
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联用
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PD-1 抑制剂 Keytruda +Nectin-4 ADC 药物 Padcev
|
借助 ADC 的靶向杀伤效应与 PD-1/PD-L1 抑制剂的免疫激活作用,实现协同抗肿瘤效果,提升治疗响应
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Human PD-L1, His Tag on SDS-PAGE under reducing (R) condition. The gel was stained with Coomassie Blue. The purity of the protein is greater than 98% (With Star Ribbon Pre-stained Protein Marker).
The purity of Human PD-L1, His Tag (Cat. No. PD1-H5229) is more than 90% and the molecular weight of this protein is around 30-50kDa verified by SEC-MALS.
Report
Loaded Human PD-1, Fc Tag, low endotoxin (Cat. No. PD1-H5257) on Protein A Biosensor, can bind Human PD-L1, His Tag (Cat. No. PD1-H5229) with an affinity constant of 5.3 μM as determined in BLI assay (ForteBio Octet Red96e) (QC tested).
Protocol
Immobilized cell surface PD-1 (5x104 of cells per well) can bind Human PD-L1, Fc Tag (Cat. No. PD1-H5258) with an EC50 of 0.029 μg/mL (Routinely tested).
Protocol
Immobilized Biotinylated Human PD-L1, Avitag,His Tag (Cat. No. PD1-H82E5) at 1 μg/mL (100 μL/well) on Streptavidin (Cat. No. STN-N5116) precoated (0.5 μg/well) plate, can bind Anti-PD-L1 MAb, Human IgG1 with a linear range of 0.2-3 ng/mL (Routinely tested).
Protocol
Anti-Human PD-L1 Mab (Human IgG1) captured on CM5 chip via anti-human IgG Fc antibodies surface, can bind Human PD-L1, His Tag (Cat. No. PD1-H5229) with an affinity constant of 0.286 nM as determined in a SPR assay (Biacore T200) (Routinely tested).
Protocol
Immobilized Human PD-1, His Tag (Cat. No. PD1-H5221) at 5 μg/mL, add increasing concentrations of Cadonilimab (PD-1 x CTLA-4 bispecific antibody) and then add Biotinylated Human CTLA-4, Fc,Avitag (Cat. No. CT4-H82F3) at 0.2 μg/mL. Detection was performed using HRP-conjugated Streptavidin (Acro, Cat. No. STN-NH913) with sensitivity of 2.99 ng/mL (Routinely tested).
Protocol
Immobilized Human VEGF165, His Tag (Cat. No. VE5-H5248) at 2 μg/mL, add increasing concentrations of Ivonescimab and then add Biotinylated Human PD-1 Protein, Avitag,His Tag (Cat. No. PD1-H82E4) at 2 μg/mL. Detection was performed using HRP-conjugated Streptavidin (Acro, Cat. No. STN-NH913) with sensitivity of 2.17 ng/mL (Routinely tested).
Flow Cytometry assay shows that Human PD-1 Protein, Fc Tag (Cat. No. PD1-H5257) can bind to 293 cell overexpressing human PD-L1. The concentration of PD-1 used is 1 μg/mL (Routinely tested).
Protocol
FACS analysis shows that the binding of Human PD-L1, Fc Tag (Cat. No. PD1-H5258) to 293 overexpressing PD-1 was inhibited by increasing concentration of neutralizing Anti-PD-L1 antibody. The concentration of PD-L1 used is 10 μg/mL. The IC50 is 12.92 μg/mL (Routinely tested).
Protocol
The Human PD-1 / PD-L1 Inhibitor Screening Kit (TR-FRET) (Cat. No. FRT-P019) is suitable for the detection of PD1/PD-L1 inhibitors. It shows that both Atezolizumab, Nofazinlimab and Pembrolizumab exhibit good inhibitory activity in this TR-FRET competition assay.
Protocol
Serial dilutions of Anti-PD-L1 Neutralizing antibody (Cat. No. EP133) (1:1 serial dilution, from 2 μg/mL to 0.015625μg/mL) was added into PD-L1: Biotinylated PD-1 binding reactions. The assay was performed according to the protocol described below. Background was subtracted from data points prior to log transformation and curve fitting (QC tested).
Protocol