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® - A novel platform for functional biomarkers
A platform technology that precisely quantifies protein functions in fixed tissue and cells:
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.
PD-L1 TPS correlates poorly with patient response
Instead, patient response clearly correlates with the level of PD-1/PD-L1 interactions measured by QF-Pro®
Stratifying by QF-Pro® could increase the efficacy of immunotherapy for lung cancer by a 280%
47% of patients with a diagnosed lung cancer are not being treated adequately (850.000 people per year)
Validated Biomarkers
As a versatile platform technology, QF-Pro® can be tailored to any functional protein target of interest. We work closely with clients to design and create novel functional biomarkers in a range of indications. We are constantly working to increase our off-the-shelf repertoire of biomarkers, of which you can find some examples below:
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.
Example 1: Interaction of the immune checkpoint TIGIT/CD155 between Jurkat T cells and CHO-K1 cells.
Example 2: Activation state of Akt in clear cell renal cell carcinoma tissue.
Example 3: Interaction state of HER2/HER3 in clear cell renal cell carcinoma tissue.
This project has been co-funded by the European Union’s Horizon Europe research and innovation programme under grant agreement Nº101161495.
“Co-funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them.”
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