The first commercial PD1/PD-L1 interaction and phosphorylated PD1 in situ assays are now launched.

PD1/PD-L1 signaling has proven to be significant in cancer progression, and immune checkpoint inhibitors targeting PD1/PD-L1 have emerged as essential therapies for cancer patients.1 But despite the success, many patients do not benefit from these therapies, and predictive biomarkers improving patient stratification are needed.1-3 Today, the leading technology used to determine whether a patient is likely to benefit from PD1/PD-L1 immunotherapy is PD-L1 immunohistochemistry (IHC). However, existing PD-L1 assays are insufficiently standardized, and PD-L1 positivity of patient samples doesn’t directly correlate with activation of the inhibitory pathway or patient response to immune-check inhibitors.3 PD1/PD-L1 interaction has predictive value for patient prognosis and survival. Still, up until now, the possibilities to detect it in tissue samples have been very limited3.

PD1 activation is an essential step in the signaling pathway and requires PD1 to be both bound to PD-L1 as well as phosphorylated 4, 5, yet phosphorylation of PD1 in situ is not well studied, mainly due to a lack of specific methods.

Here is how our newly developed in situ assays make a difference. Navinci has developed two Proximity Ligation Assays for the specific detection of the PD1/PD-L1 interaction and phosphorylated PD1.

The NaveniTM PD1/PD-L1 was validated using human FFPE tissue. The PD1/PD-L1 interaction was verified in: Tonsil, Acinar Adenocarcinoma lung, Squamous cell lung carcinoma, Malignant Melanoma, Colon adenocarcinoma, and Pancreatic ductal adenocarcinoma.

Protein-protein interaction (PPI): Proximity Ligation assay for detection of PD1/PD-L1 interaction
PD1/PD-L1 interaction - Tonsil
PD1/PD-L1 interaction - Pancreatic ductal adenocarcinoma
PD1/PD-L1 interaction - Pancreatic adenocarcinoma
PD1/PD-L1 interaction - Squamous cell lung carcinoma
PD1/PD-L1 interaction - Malignant melanoma
PD1/PD-L1 interaction - colon adenocarcinoma
PD1/PDL1 interaction -Acinar adenocarcinoma lung

The NaveniTM pY PD1 was validated in human FFPE, Tonsil tissue, and compared with IHC. NaveniTM pY PD1 specifically detects phosphorylated PD1. IHC staining of phosphorylated PD1 gave unspecific staining.

Protein post-translational modifications (PTM): Proximity Ligation assay for detection of phosphorylated PD1
Phosphorylated PD1 - Tonsil
Naveni pY PD1 staining of pPD1 in tonsil tissue
Immunohistochemistry staining of pPD1 in the same tonsil tissue

Description of the kits 

The two target-specific Naveni kits are in situ proximity ligation assay kits with bright-field read-out. The kits give a high signal-to-noise ratio and are based on dual antibody recognition enabling high specificity. These target-specific kits have everything included and are optimized

The kits are based on our NaveniTM Proximity Ligation Technology, with two Navenibodies conjugated to proprietary oligo arms. The technology ensures specific and sensitive detection; learn more about our technology on Naveni platform. 

Included in the kit: 

  • Two Navenibodies targeting the protein of interest  
  • Detection with HRP or AP substrate. Choose your preferred detection system. 
  • Buffers for blocking and dilutions, and all detection reagents 
  • The Navenibody solution has a working volume of 4000µl (sufficient for approx. 100 reactions) 

Our PD1 products

Navinci Technology 

Learn how to maximize information from every analysis by localizing and quantifying proteins, their interactions, and modifications in situ at a molecular level. In situ methods are commonly used in the cancer research field, and studies of protein-protein interactions (PPI) and protein translational modifications (PTM) are essential for: 

  • Deep biological knowledge 
  • Biomarker discovery
  • Patient stratification
  • Drug testing
  • Treatment validation 

All our products are based on our proprietary Naveni Proximity Ligation technology with dual antibody recognition giving you more specific and sensitive detection of your target of interest. Click here to read about the technology. 

To our flexible products – to use with your primary antibodies 

To our specific products – for the precise detection of phosphorylated Met, VEGFR2, EGFR, HER2, and PDGFR-beta. 

References

1.Pu Y, Ji Q. Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression. Front Immunol. 2022 May 3;13:874589. ​

2.Robert C, A decade of immune-checkpoint inhibitors in cancer therapy. Nat Commun. 2020; 11: 3801​

3.Sánchez-Magraner L, et al. High PD-1/PD-L1 Checkpoint Interaction Infers Tumor Selection and Therapeutic Sensitivity to Anti-PD-1/PD-L1 Treatment. Cancer Res. 2020 Oct 1;80(19):4244-4257​

4.Patsoukis N, et al. Revisiting the PD-1 pathway. Sci Adv 2020 Sep 18;6(38)​

5.Patsoukis N, et al. Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. Commun Biol. 2020 Mar 17;3(1):128.