Check specificity on PDL-1/PD1 interaction in-vitro, then move on to in-vivo!
Treating cancer by using our own defense mechanism, the immune system, is a rapidly developing concept known as immunotherapy.
Activated T cells are primary mediators whose activity is tightly regulated by a balance between co-stimulatory and inhibitory signals that are controlled by specific complexes known as immune checkpoints. The main regulators of immune activation, they play a key role in maintaining immune homeostasis.
In cancer, however, immune checkpoint mechanisms are often activated to suppress nascent anti-tumor immune response. This has led to the development of several checkpoint inhibitor antibody drugs that are currently being tested in clinical trials or already FDA approved. Impairing the interaction between programmed-death ligand 1 (PD-L1) and its receptor (PD1), one of the most well-described immune checkpoints, represents a very attractive immunotherapeutic approach. Molecular imaging is the gold standard technique for tracking tumor progression and checking treatment efficacy.
How can you easily detect tumors expressing a high level of PD-L1? Samit Chatterjee and his team developed a copper-64 labeled WL12 ([64Cu]WL12) peptide that binds to PD-1. By using recombinant tagged-proteins in a PD-L1/PD 1 binding inhibition assay, the team first confirmed the potency of this peptide in-vitro. Peptide up-take was also confirmed in CHO cells stably expressing human PD-L1. Lastly, they showed the specific distribution of this labelled peptide at the tumor site, in-vivo, using the molecular PET-CT imaging of mouse xenograft.
Do you need a probe to easily monitor the effect of therapeutics targeting PD1/PD-L1? WL12 peptide is the answer!
Molecular imaging can report on the status of the tumor immune microenvironment and guide immunotherapeutic strategies to enhance the efficacy of immune modulation therapies. Imaging agents that can rapidly report on targets of immunomodulatory therapies are few. The programmed death ligand 1 (PD-L1) is an immune checkpoint protein over-expressed in several cancers and contributes to tumor immune suppression. Tumor PD-L1 expression is indicative of tumor response to PD-1 and PD-L1 targeted therapies. Herein, we report a highly specific peptide-based positron emission tomography (PET) imaging agent for PD-L1. We assessed the binding modes of the peptide WL12 to PD-L1 by docking studies, developed a copper-64 labeled WL12 ([64Cu]WL12), and performed its evaluation in vitro, and in vivo by PET imaging, biodistribution and blocking studies. Our results show that [64Cu]WL12 can be used to detect tumor PD-L1 expression specifically and soon after injection of the radiotracer, to fit within the standard clinical workflow of imaging within 60 min of administration.
Biochemical Biophysical Research Communication. 2017 Jan 29;483(1):258-263.