PD-1:PD-L1/L2/ & PD-L1: B7-1 Screening

BPS provides PD-1 biochemical and cell-based screening and profiling services. Biochemical screening services provide a great initial screen to find small molecules or biologics that prevent PD-1 from binding to its ligands; PD-L1, PD-L2, and B7-1. Then, the most promising hits can be further screened in our PD-1 reporter cell-based assay which offers a functional readout of the result (agonistic vs antagonistic) on PD-1 signaling. Trust us to provide you with high quality data with fast turnaround time. Our team of experts along with our broad services portfolio makes it easy to:

  • Screen for inhibitors/targets using our PD-1 assays
  • Select from IC50 determination and single point concentrations
  • Receive data within days of compound submission
  • Perform follow-up studies using the same soluble receptors manufactured in-house
  • Get questions answered or project guidance in a time-efficient manner

Contact BPS today to find out more about how we can assist you in your PD-1 related research.

Biochemical Assay Format:

Cell-Based Assay Format: 

Jurkat T cells stably expressing human PD-1 and NFAT responsive luciferase reporter are used as effector cells; HEK293 cells over-expressing PD-L1 or PD-L2 and an engineered TCR activator are used as target cells. When these two cells are co-cultivated, TCR complexes on effector cells are activated by TCR activator in target cells, resulting in expression of NFAT luciferase reporter. However, PD-1:PD-L1/PD-L2 ligation prevents TCR activation and suppresses the NFAT responsive luciferase activity (Fig. 1a). This inhibition can be specifically reversed by anti- PD1 or anti-PD-L1 Ab (Fig 1b). PD-1 or PD-L1 neutralizing Ab blocks PD-1:PD-L1 interaction and therefore promotes T cell activation, resulting in re-activated NFAT responsive luciferase reporter.

This reporter based PD-1 cell based assay provides a tool for PD-1 drug screening and characterization that complements BPS' PD-1 biochemical screens.

Background: 

Programmed cell death protein 1, or PD-1, is a protein which helps to regulate the immune system. PD-1 can bind to either PD-L1 or PD-L2 and as a result, inhibits T cell activation and other pro-inflammatory processes. This inhibition is accomplished through increasing apoptosis of T-cells and preventing apoptosis of suppressor T cells. PD-1 ligands are often over expressed in various types of cancer. Overexpression of PD-1 ligands helps cancer cells evade the immune system. As a result, PD-1 inhibitors have become an important target in immuno oncology.


In September of 2014, the first PD-1 antagonistic antibody, pembrolizumab (KeytrudaTM, Merck) was approved for the treatment of advanced melanoma under the FDA Fast Track Development Program[1] . In December of that same year, yet another PD-1 antagonistic antibody, nivolumab (OpdivoTM, Bristol-Myers Squibb) was approved for advanced melanoma[2] . Since their approval, PD-1 neutralizing antibodies have resulted in unprecedented response and survival rates in previously untreatable cancers. In addition to PD-1 neutralizing antibodies, the FDA recently approved the anti-PD-L1 antibody, atezolizumab (TecentriqTM, Roche) for the treatment locally advanced or metastatic urothelial carcinoma (mUC [3]).

BPS Bioscience offers many different types of PD-1 assay kits for screening inhibitors of PD-1:PD-L1 or PD-L2 interaction:

 

Not quite what you're looking for? We also offer custom assays for several other immunotherapy targets. Our Custom Assay Development Services allow for flexibility to meet your specific research needs

References

1. U.S. Food and Drug Administration (September 4, 2014). "FDA approves Keytruda for advanced melanoma". U.S. Food and Drug Administration. U.S. Food and Drug Administration. Retrieved 24 December2015.

2. Johnson DB, Peng C, Sosman JA (2015)."Nivolumab in melanoma: latest evidence and clinical potential"Ther Adv Med Oncol 7 (2): 97–106.doi:10.1177/1758834014567469PMC 4346215.PMID 25755682.

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