tyc122ccvip

针对癌症治疗的双特异性抗体靶向免疫调节检查点

免疫检查点抑制剂(ICIs)的开发彻底改变了癌症治疗标准,其中阻断 PD-1/PD-L1 信号是当前最成功的免疫治疗策略之一。然而,ICIs 的临床应用仍面临挑战:仅少数患者能获得持久应答,且正常组织中抑制性与共刺激性信号失衡,导致免疫相关不良反应(irAE)发生率较高及耐药性问题。
研究表明,开发靶向免疫检查点的新型双特异性抗体(bsAbs)是克服这些挑战的有效策略。这类双抗可同时结合两个不同表位,通过阻断多个免疫检查点解决其间的补偿机制,从而增强治疗效果。此外,与单抗及联合用药相比,双抗能更精准桥连免疫细胞与肿瘤细胞,避免 T 细胞广泛激活,降低脱靶效应,减少副反应及用药剂量。
为了助力相关研究,ACROBiosystemstyc122ccvip开发了500+免疫检查点蛋白tyc122ccvip、过表达/报告基因细胞系、抑制剂筛选试剂盒和PK血药浓度检测试剂盒,这一系列tyc122ccvip可满足从免疫、抗体筛选和表征、稳定性测定到后期的生产质控全流程,协助加速免疫疗法研发。
The bsAbs targeting immunomodulatory checkpoints

The bsAbs targeting immunomodulatory checkpoints. The checkpoint-targeted bsAbs are mainly divided into three categories: targeting dual inhibitory checkpoints (①); targeting co-stimulatory and inhibitory checkpoints (②); and targeting immunomodulatory checkpoints and non-checkpoint targets (③④).
Source:doi: 10.20892/j.issn.2095-3941.2023.0002

靶向免疫检查点双抗的分类

免疫检查点可分为共刺激和共抑制两类。癌细胞异常表达的抑制性检查点是免疫逃逸和药物耐药的基础。靶向免疫检查点的双抗主要可分为靶向双抑制性免疫检查点、靶向共刺激和抑制性检查点及靶向免疫调节检查点和非检查点这几类。
靶向双抑制性免疫检查点
靶向双抑制性免疫检查点
靶向双共刺激免疫检查点
靶向双共刺激免疫检查点
靶向共刺激和抑制性免疫检查点
靶向共刺激和抑制性免疫检查点
靶向免疫检查点和细胞因子及其受体
靶向免疫检查点和细胞因子及其受体
靶向免疫检查点和TAA
靶向免疫检查点和TAA
靶向免疫检查点和其他非免疫检查点
靶向免疫检查点和其他非免疫检查点

验证数据

SEC-MALS验证蛋白结构和纯度
SEC-MALS验证蛋白结构和纯度

The purity of Human CTLA-4, His Tag (Cat. No. CT4-H52H9) is more than 90% and the molecular weight of this protein is around 45-60 kDa verified by SEC-MALS.

SEC-MALS验证蛋白结构和纯度

The purity of Biotinylated Human 4-1BB, His,Avitag (Cat. No. 41B-H82E6) is more than 90% and the molecular weight of this protein is around 25-35 kDa verified by SEC-MALS.

与双抗结合活性经ELISA验证
与双抗结合活性经ELISA验证

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

与双抗结合活性经ELISA验证

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).

Protocol

与抗体的结合活性经ELISA验证
与抗体的结合活性经ELISA验证

Immobilized Human LAG-3, His Tag (Cat. No. LA3-H5222) at 2 μg/mL (100 μL/well) can bind Monoclonal Anti-Human LAG3 Antibody, Human IgG1 with a linear range of 0.2-4 ng/mL (QC tested).

Protocol

与抗体的结合活性经ELISA验证

Immobilized Human PD-1, His Tag (Cat. No. PD1-H5221) at 2 μg/mL (100 μL/well) can bind Nivolumab with a linear range of 0.1-3 ng/mL (Routinely tested).

Protocol

与抗体的结合活性经BLI/SPR验证
与抗体的结合活性经SPR/BLI验证

Loaded Anti-OX40 MAb(Human IgG1) on AHC Biosensor, can bind Human OX40 Protein, His Tag (Cat. No. OX0-H5224) with an affinity constant of 6.03 nM as determined in BLI assay (ForteBio Octet Red96e) (Routinely tested).

Protocol

与抗体的结合活性经SPR/BLI验证

Anti-LAG-3 MAb (Human IgG1) captured on CM5 chip via Anti-Human IgG Fc antibodies surface, can bind Human LAG-3, His Tag (Cat. No. LA3-H5222) with an affinity constant of 4.57 nM as determined in a SPR assay (Biacore T200) (Routinely tested).

Protocol

中和抗体筛选
中和抗体筛选

Serial dilutions of Human TIGIT Neutralizing antibody were added into Human TIGIT, Fc Tag (Cat. No. TIT-H5254): Biotinylated Human CD155, Fc,Avitag (Cat. No. CD5-H82F6) binding reactions. The half maximal inhibitory concentration (IC50) is 0.55834 μg/mL (Routinely tested).

Protocol

中和抗体筛选

FACS analysis shows that the binding of Human SIRP alpha, His Tag (Cat. No. SIA-H5225) to Jurkat expressing CD47 was inhibited by increasing concentration of neutralizing Anti-CD47 antibody. The concentration of SIRP alpha used is 1 μg/mL.

Protocol
药代动力学分析-PK分析
药代动力学分析-PK分析

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

药代动力学分析-PK分析

Quantitative Analysis of CTLA-4 x OX40 Bispecific Antibody in Human Serum by Intact Assay Immobilized Human CTLA-4, His Tag, active dimer (Cat. No.CT4-H52H9) at 2 μg/mL, add increasing concentrations of CTLA-4 x OX40 Bispecific Antibody in 50% Human serum and then add Biotinylated Human OX40, Avitag,His Tag(Cat. No. TN4-H82E4) at 1 μg/mL. Detection was performed using HRP-conjugated streptavidin with sensitivity of 4 ng/mL (Intact assay, Routinely tested).

Protocol

资源分享

  • 背景
  • 靶向免疫检查点双抗的分类
  • 验证数据
  • 资源分享