Chris Sale, CEO of Nonacus
Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, and the University of Birmingham have partnered to develop a non-invasive urine test for bladder cancer. The test, which is expected to be available by mid-2022, will use highly sensitive liquid biopsy technology developed by Nonacus, and a panel of biomarkers validated by Dr Rik Bryan and Dr Douglas Ward from the university’s Bladder Cancer Research Centre, to diagnose the disease from urine samples.
Chris Sale, CEO of Nonacus, commented: “We expect this partnership to deliver better care and outcomes for patients by reducing the number of invasive procedures, providing earlier diagnosis and speeding up access to treatment for people with bladder cancer.”
Haematuria
Bladder cancer is the seventh most common cancer in the developed world [1]. In the UK, over 100,000 people a year are referred to hospital clinics that investigate for bladder cancer, usually after passing blood in their urine (haematuria). The first stage of investigation is usually cystoscopy, which involves inserting a camera into the bladder. Of these 100,000 patients, around 12% are subsequently diagnosed with bladder cancer, normally after a second invasive procedure to extract a biopsy.
Dr Bryan, Director of the Bladder Cancer Research Centre, commented: “While blood visible in the urine should always be investigated, over 80% of people who have a cystoscopy at a haematuria clinic are diagnosed with non-malignant conditions or have no abnormality. Unfortunately, the remaining 20% will need a further invasive procedure to confirm diagnosis. What is required is a highly sensitive and specific, non-invasive test that can rapidly determine those who need a biopsy and those who do not, and a urine test is the obvious place to start.”
While the ‘liquid biopsy’ approach is attractive, the low levels of tumour DNA in a background of DNA from normal tissues requires highly sensitive analytical techniques to obtain accurate results. However, researchers at the University of Birmingham started their work in the knowledge that Nonacus had successfully pioneered commercial non-invasive prenatal tests to identify low-levels of foetal DNA in maternal blood samples. Moreover, the company was developing methods to allow confident and sensitive calling of mutations from as little as 10ng of DNA.
Deep sequencing of tumour DNA
The researchers used ‘deep sequencing’ of tumour DNA to identify mutations that are present in the majority of urothelial bladder cancers (UBCs). Their work, which was funded by Cancer Research UK and an MRC Confidence in Concept grant, involved sequencing 23 genes from tumour samples collected from 956 newly diagnosed, treatment-naïve patients. This deep sequencing of genes identified 451 unique mutations that were present in over 96% of tumours. The researchers also demonstrated that these mutations were identifiable in urine samples collected at the same time as tumour sampling [2].
As the researchers have shown, mutated DNA in a urine sample can be extracted from cancer cells shed into the urine from the lining of the urinary tract, or can be found as cell-free DNA fragments [2]. However, extracting DNA from the cancer cells provides more reliable amounts of DNA for the test, especially when only small volumes of urine may be available. Coupling the mutation panel with the unique molecular identifiers and the proprietary target capture technology provided by the Nonacus Cell3 Target™ will provide a much more sensitive test than the existing PCR-based approach. The researchers are already working on validating this combination in a further 600 cases (including non-cancer cases) and they expect to publish data on sensitivity and specificity within six months.
Nonacus intends to launch the new bladder cancer test within 12 months, and the final product will include access to bioinformatics software to help with analysis. The company expects the test will provide high sensitivity for all stages and grades of disease, and will ensure the test is available worldwide to laboratories, hospitals and clinics.
Influence of mutations on cancer progression
Promisingly, the original research also determined the influence of the mutations on cancer progression, time to recurrence, and overall and disease-specific survival in patients with non-muscle-invasive bladder cancer (NMIBC), and disease-specific survival in patients with muscle-invasive bladder cancer (MIBC), raising the possibility that the test could be used to stratify patients according to risk.
Allen Knight, Chair of Trustees, Action Bladder Cancer UK, said: “This really is very exciting and has the potential to make an incredible difference for patients and for Bladder Cancer treatment. Currently urine tests do not accurately pick up bladder cancer, and invasive tests are required to confirm a diagnosis. A urine test that can rapidly determine who needs these tests will be a very welcome development. Many patients, myself included, find cystoscopies very uncomfortable at best, and they can have lasting side effects. This research could pave the way for routine screening, common in other cancers, but unavailable at present for Bladder Cancer.”
References
[1] Antoni, S. et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 2017; 71: 96–108.
[2] Bryan RT et al. Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA: a 23 gene panel with utility for non-invasive diagnosis and risk stratification. BJU Int 2019: 124; 532-544.
Speeding up flow cytometry in clinical development
, /in Featured Articles /by panglobalFlow cytometry is one of many analytical techniques used in clinical development to help discover new biomarkers and aid in development of new therapies. This article highlights how automated gating can expedite data processing and management, leading to improved productivity and insights in flow cytometry analysis for clinical research.
Developments in optical fibre imaging: nano-ultrasonography and more
, /in Featured Articles /by panglobalOptical fibres have revolutionized clinical practice in the form of the optical endoscope, and are now providing the framework for an entirely new endoscopic paradigm: all-optical ultrasound. Here we describe a phonon probe, which offers a route towards cellular resolution acoustic imaging – while also offering new capabilities such as label-free contrast and parallel spectroscopy […]
Basic Metabolic Panel. STAT.
, /in Advertenties /by Instrumentation LaboratoryHemostasis automation that works on so many levels
, /in Advertenties /by Instrumentation LaboratoryEpigenetic diagnostics and preventive medicine
, /in Featured Articles /by panglobalAlthough we have a reasonable understanding of a number of mechanisms of epigenetic regulation, we are still have a lot more to learn about the impact and influence of epigenetic regulation, particularly in relation to disease. CLI caught up with Professor Michael Skinner (Center for Reproductive Biology, Washington State University, USA) to find out more […]
We’ve got your back! Real human constituents,unreal stability.
, /in Advertenties /by Quantimetrix CorpNova POC Creatinine/eGFR Method is More Accurate than Laboratory Method: Large Medical Center Study
, /in Advertenties /by Nova Biomedical Corp.Porvair Sciences expands range of microplate products for SARS-CoV-2 nucleic acid purification
, /in Product News /by panglobalPorvair Sciences has further expanded its range of high-performance microplate products for SARS-CoV-2 nucleic acid purification.
The new KF deep well plate and tip comb plate combo are specifically designed to enhance the performance and productivity of the market-leading Thermo Scientific KingFisher range of nucleic acid purification systems.
Krzysztof Kielmann, microplates product manager at Porvair Sciences commented: “The Kingfisher Flex and Duo Prime systems have a number of design features that make the design of the deep well and the protective tip comb plate crucial to the correct operation of the instrument. Our optimised deep well plate has small gaps that align to locating pins on the Kingfisher instrument and the bottom profile of the 96 wells is designed to fit the heater block providing close contact and sample temperature control.
“The protective polypropylene tip comb is designed specifically for the 96 magnetic probes of the Kingfisher magnetic particle processor. The magnet slides into the disposable 96 well comb dips. Our KF deep well plate together with the protective tip comb plate has been shown to significantly improve the yield and quality of the isolated protein or nucleic acid when used on KingFisher systems.”
The KF range of low affinity deep well plates and protective tip cone plate are manufactured in a cleanroom production environment using ultra-pure polypropylene that has the lowest leachables, extractables and is free from DNase and RNase. This allows SARS-CoV-2 test samples to be purified with the confidence of no risk of contamination or interference during the magnetic particle processing used by KingFisher nucleic acid purification systems.
BBI Solutions markets first chimeric Jo-1 HumAb IgG
, /in Product News /by panglobalBBI Solutions has launched a new Jo-1 human chimeric antibody for use as a calibrator or positive control in assays to diagnose conditions such as connective tissue disease (CTD).
BBI has used cell culture technologies in response to the concerning situation, as hospital visits continue to be dominated by Covid-related cases, leading to a drop in supplies of positive patient materials for certain markers, which are commonly used for calibrators and controls in IVD assays.
Idiopathic inflammatory myopathies
Autoantibodies against the aminoacyl-tRNA synthetase Jo-1 can be found in up to 20% of patients with idiopathic inflammatory myopathies (IIM), a sub-form of CTD [1]. Jo-1 is therefore the most prevalent marker found in IIM.
Anti-synthetase autoantibodies, such as Jo-1 autoantibodies, are also strongly associated with interstitial lung disease (ILD) which makes an early diagnosis on a component level even more important.
It is the only commercially available Jo-1 human chimeric monoclonal antibody available on the market for companies which manufacture diagnostic tests.
Mario Gualano, CEO of The BBI Group, said: “The introduction of Jo-1 HumAb IgG further strengthens our wide portfolio of CTD products in our autoimmune range. This product will help support IVD companies to realise the growth in the autoimmune diagnostic testing market.”
Human chimeric monoclonal antibodies
Human chimeric monoclonal antibodies can be used as an alternative to characterised disease state plasma. They are produced in transgenic mouse strains in which the sequence for mouse IgG1 Fc region is substituted with the human sequence. After mouse immunisation and use of hybridoma technology, antibodies are generated that retain a human constant region required for recognition by the anti-human IgG detection antibody.
Simon Packer, Product Manager for Antigens at BBI Solutions, explained: “Currently fewer people are visiting hospitals for diseases and conditions other than Covid-19. This is affecting supplies of positive patient materials for certain markers, which are commonly used for calibrators and controls in IVD assays. That is why bringing new chimeric antibodies to the market, at this time, is crucially important to ensure a reliable sustained supply.
“Our Jo-1 HumAb IgG has been developed with the same rigour as our other human chimeric monoclonal antibodies. The mouse monoclonal variable region was carefully defined for Jo-1 and this was integrated with the human constant region in a stabilised cell line. The material is produced using cell culture In-Vitro, meaning there is a continuous steady supply and consistent assay performance, making it a reliable alternative to characterised disease state plasma.
“It has been proven to show equivalent sensitivity to anti-Jo-1 positive patient samples, even at high dilution using our Histidyl-tRNA Synthetase (Jo-1) antigen. So, you can be satisfied that our Jo-1 HumAb IgG works as effectively as characterised disease state plasma.”
Birmingham University, Nonacus partner to develop urine test for bladder cancer
, /in E-News /by panglobalChris Sale, CEO of Nonacus
Nonacus, a provider of genetic testing products for precision medicine and liquid biopsy, and the University of Birmingham have partnered to develop a non-invasive urine test for bladder cancer. The test, which is expected to be available by mid-2022, will use highly sensitive liquid biopsy technology developed by Nonacus, and a panel of biomarkers validated by Dr Rik Bryan and Dr Douglas Ward from the university’s Bladder Cancer Research Centre, to diagnose the disease from urine samples.
Chris Sale, CEO of Nonacus, commented: “We expect this partnership to deliver better care and outcomes for patients by reducing the number of invasive procedures, providing earlier diagnosis and speeding up access to treatment for people with bladder cancer.”
Haematuria
Bladder cancer is the seventh most common cancer in the developed world [1]. In the UK, over 100,000 people a year are referred to hospital clinics that investigate for bladder cancer, usually after passing blood in their urine (haematuria). The first stage of investigation is usually cystoscopy, which involves inserting a camera into the bladder. Of these 100,000 patients, around 12% are subsequently diagnosed with bladder cancer, normally after a second invasive procedure to extract a biopsy.
Dr Bryan, Director of the Bladder Cancer Research Centre, commented: “While blood visible in the urine should always be investigated, over 80% of people who have a cystoscopy at a haematuria clinic are diagnosed with non-malignant conditions or have no abnormality. Unfortunately, the remaining 20% will need a further invasive procedure to confirm diagnosis. What is required is a highly sensitive and specific, non-invasive test that can rapidly determine those who need a biopsy and those who do not, and a urine test is the obvious place to start.”
While the ‘liquid biopsy’ approach is attractive, the low levels of tumour DNA in a background of DNA from normal tissues requires highly sensitive analytical techniques to obtain accurate results. However, researchers at the University of Birmingham started their work in the knowledge that Nonacus had successfully pioneered commercial non-invasive prenatal tests to identify low-levels of foetal DNA in maternal blood samples. Moreover, the company was developing methods to allow confident and sensitive calling of mutations from as little as 10ng of DNA.
Deep sequencing of tumour DNA
The researchers used ‘deep sequencing’ of tumour DNA to identify mutations that are present in the majority of urothelial bladder cancers (UBCs). Their work, which was funded by Cancer Research UK and an MRC Confidence in Concept grant, involved sequencing 23 genes from tumour samples collected from 956 newly diagnosed, treatment-naïve patients. This deep sequencing of genes identified 451 unique mutations that were present in over 96% of tumours. The researchers also demonstrated that these mutations were identifiable in urine samples collected at the same time as tumour sampling [2].
As the researchers have shown, mutated DNA in a urine sample can be extracted from cancer cells shed into the urine from the lining of the urinary tract, or can be found as cell-free DNA fragments [2]. However, extracting DNA from the cancer cells provides more reliable amounts of DNA for the test, especially when only small volumes of urine may be available. Coupling the mutation panel with the unique molecular identifiers and the proprietary target capture technology provided by the Nonacus Cell3 Target™ will provide a much more sensitive test than the existing PCR-based approach. The researchers are already working on validating this combination in a further 600 cases (including non-cancer cases) and they expect to publish data on sensitivity and specificity within six months.
Nonacus intends to launch the new bladder cancer test within 12 months, and the final product will include access to bioinformatics software to help with analysis. The company expects the test will provide high sensitivity for all stages and grades of disease, and will ensure the test is available worldwide to laboratories, hospitals and clinics.
Influence of mutations on cancer progression
Promisingly, the original research also determined the influence of the mutations on cancer progression, time to recurrence, and overall and disease-specific survival in patients with non-muscle-invasive bladder cancer (NMIBC), and disease-specific survival in patients with muscle-invasive bladder cancer (MIBC), raising the possibility that the test could be used to stratify patients according to risk.
Allen Knight, Chair of Trustees, Action Bladder Cancer UK, said: “This really is very exciting and has the potential to make an incredible difference for patients and for Bladder Cancer treatment. Currently urine tests do not accurately pick up bladder cancer, and invasive tests are required to confirm a diagnosis. A urine test that can rapidly determine who needs these tests will be a very welcome development. Many patients, myself included, find cystoscopies very uncomfortable at best, and they can have lasting side effects. This research could pave the way for routine screening, common in other cancers, but unavailable at present for Bladder Cancer.”
References
[1] Antoni, S. et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 2017; 71: 96–108.
[2] Bryan RT et al. Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA: a 23 gene panel with utility for non-invasive diagnosis and risk stratification. BJU Int 2019: 124; 532-544.