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Discover how QF-Pro® is transforming clinical biomarker research
Understanding the intricate interactions of proteins is crucial for deciphering biological processes. Proteins govern a plethora of functions and serve as pivotal targets in health and disease. QF-Pro® not only enhances our understanding of biological pathways and protein functional states but also facilitates the identification of new biomarkers at single-cell resolution. Moreover, it enables deep phenotypic profiling in both cell and tissue models, providing early insights into drug mechanism of action and facilitating precise drug target engagement in tissues.
QF-Pro® can be used in order to quantify a range of protein-protein interactions (PPIs) within tissue samples.
This includes intracellular PPIs such as HER2/HER3 dimerisation or Akt/PDK1 interaction states. QF-Pro® can also quantify intercellular interaction states such as those of immune checkpoints, i.e., PD-1/PD-L1, CTLA-4/CD80, TIGIT/CD155.
These intercellular PPIs are quantified in-situ without the need for cell permeabilisation. Other interaction states that can be quantified include DNA-protein interactions.
Our intracellular PTM assays quantify events such as the phosphorylation or methylation states of intracellular proteins. The spatial mapping of these PTMs allows the user to quantify the functional states (e.g. activation) of proteins within samples. PTMs that can be quantified by QF-Pro® also include glycosylation and acetylation events. These readouts are particularly useful for gaining insights on intracellular signalling pathway dynamics and designing small molecule therapeutics.
Optimised biomarkers include Akt activation state, PD1 activation state and STAT3 (Y705 or S727) activation state quantification.
Immuno-Oncology
Our technology has demonstrated a direct clinical value in the domain of immuno-oncology. Immune checkpoints, such as PD-1/PD-L1, provide a key mechanism to target cancer, by re-enabling the hosts immune system to fight and destroy malignant cells. However, only 12-20% of solid tumour patients respond to these therapies and the lack of a robust biomarker to indicate which patients will or will not respond to these immunotherapies only contributes to worsen this situation.
Published in the Journal of Clinical Oncology in 2023, we have validated a QF-Pro® assay for the determination of PD-1/PD-L1 interaction state (functional checkpoint engagement) in non-small cell lung cancer (NSCLC). In this study of 188 patients, PD-1/PD-L1 interaction state measured by QF-Pro®, but not PD-L1 expression TPS, was highly predictive of patient outcome and response to immune checkpoint blockade treatments.
QF-Pro® identified that patients with a high PD-1/PD-L1 interaction state in their biopsy samples (as quantified by QF-Pro®) responded positively to immune checkpoint blockade, irrespective of their PD-L1 expression. This accounts for almost 25% of all NSCLC patients who would therefore not routinely be selected for therapy despite responding.
Our QF-Pro® analyses were compared to classical PD-L1 expression scores (TPS) determined by IHC. PD-L1 TPS alone did not predict response to immune checkpoint inhibitors. Moreover, in this study, 22.5% of NSCLC patients with high PD-L1 expression but low PD-1/PD-L1 interaction state QF-Pro® read-outsfailed to respond to therapies. Thus, if QF-Pro® would be used to stratify NSCLC patients to IO treatments, it could significantly boost patient response rates to these treatments.
Case Studies
QF-Pro® has also been validated in several clinical studies. Please view ‘Our Papers’ to see a selection of research outputs which have featured QF-Pro® technology.
QF-Pro® could predict patients’ response to immunotherapy in lung cancer. In a study published in Journal of Clinical Oncology in 2023, we showcased the ability of QF-Pro® to predict patient response to anti-PD-1/PD-L1 therapies by directly quantifying the interaction state of this immune checkpoint directly within patient biopsy samples. The results were ground-breaking. QF-Pro® could triple response rates and double overall survival rates compared to the current clinical gold-standard, PD-L1 TPS score.
Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation. In a novel study, published in the journal Cancers, QF-Pro® quantified the interaction states of PD-1/PD-L1 and CTLA-4/CD80 in radiofrequency ablations (RFA)-treated lung metastases. This was the first time CTLA-4/CD80 interaction states had been spatially quantified in tissue samples, and showcased a potential route to select patients who would benefit from RFA and ICI dual therapy treatments.
QF-Pro® was applied, for the first time, to quantify the interaction states of PD-1/PD-L1 (in cells and FFPE tissues) and CTLA-4/CD80 (in cells). In this study, QF-Pro® technology was validated as a proof of concept for these two interactions showing great sensitivity and specificity. Moreover, QF-Pro® could predict patient overall survival in melanoma and lung cancer. Strikingly, in renal cancer, QF-Pro® outperformed the Proximity Ligation Assay (PLA) technology for the detection and quantification of these interactions.
In this novel experimental set up, we spatially mapped the interaction state of PD-1/PD-L1 between melanoma cells and cell-membrane on tissue microarrays. This showcased the utility of membrane microarrays in combination with the quantification of spatial functional proteomics.
QF-Pro® quantified the activation (phosphorylation) state of the oncoprotein Akt/PKB in clear cell renal cell carcinoma (ccRCC). This provided a prognostic tool capable of predicting overall survival in patients, with those patients with a higher activation state of Akt/PKB showing significantly poorer survival. Akt/PKB was originally discarded as a prognostic biomarker by the scientific community when only its expression was measured. This study exhibited the power of using functional spatial proteomics to map biomarker functionality within samples.
What is QF-Pro®?
Learn about Quantifying Functions in Proteins (QF-Pro®) and how our advanced bio-imaging assay can further your research outputs. Find out about how QF-Pro® works and understand which protein functional events it can quantify.
Validated Biomarkers
Find out more about the wide range of QF-Pro® validated QF-Pro® assays that we offer, ranging from immune checkpoints to kinase activation states. Our flexible technology can be applied to quantify the function of any biomarker in any disease setting.
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