On 14th November 2019 a “continuing medical education course” is organized at the Leiden University Medical Center (LUMC) entitled “Prime time for precision diagnostics driven by unmet clinical needs”. During this symposium (inter)national experts will discuss health and disease at a molecular level on the basis of Clinical Proteomics. Case studies are presented to exemplify the potential for precision diagnostics. Furthermore, it will be emphasized that clinical needs need to be defined to contribute to patient care in an efficient and effective way. www.boerhaavecontinuingmedicaleducation.com
Start Codon, a new model of life science and healthcare business accelerator, has announced its first cohort of start-up companies. Start Codon aims to minimise risk and translate early stage research into successful start-ups, ready for funding and partnership. Start Codon has worked closely with four life science and healthcare companies that were enrolled into the programme in February this year.
- Enhanc3D Genomics, a functional genomics spin-out of the Babraham Institute (Cambridge, UK) whose platform technology links non-coding sequence variants to their target genes in order to identify novel therapeutic targets
- Drishti Discoveries, a start-up leveraging a proprietary gene silencing technology to develop therapies for rare inherited diseases
- Spirea, a spin-out from the University of Cambridge, who is developing the next generation of antibody drug conjugate cancer therapeutics which carry more drug payload to tumour cells, resulting in greater efficacy, tolerability and the ability to treat more cancer patients
- Semarion, a University of Cambridge spin-out, who is revolutionising cell-based assays for drug discovery and life science through its proprietary SemaCyte microcarrier platform, which leverages novel materials physics for assay miniaturisation, multiplexing, and automation
Start Codon plans to invest in and support up to 50 start-up companies over the next five years. The accelerator is now accepting applications for its second and third cohorts of companies. Early stage start-up companies in the life sciences and healthcare space are invited to apply via https://startcodon.co/application-form
Cambridge, UK-based Horizon Discovery Group, specializing in the application of gene editing and gene modulation for cell line engineering, has released an arrayed CRISPR knockout screening service for primary human B cells to its cell-based screening services.
The new B cell screening service, the first of its kind in the market, will enable researchers to identify genes that affect the function of B cells and examine how this impacts other immune cell types, particularly in infectious diseases, cancer, and auto-immune disorders, such as COVID-19, Burkitt’s lymphoma and multiple sclerosis respectively.
Primary human cells – cells that are freshly isolated from donors – are known to be difficult to study in the lab. However, working with these cells brings scientists one step closer to healthy or diseased micro-environments, enabling them to better understand disease etiology and therapeutic mechanisms, and thereby advance drug discovery and development programs.
“The interest in harnessing the immune system for effective therapies continues to grow, with the global cell therapy market predicted to reach $8.21bn by 2025. Expanding our services to encompass screening of both primary T and B cells is another example of our commitment to apply decades of gene editing experience in support of drug discovery and development for the treatment of human disease,” said Terry Pizzie, CEO, Horizon Discovery.
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During the course of the current coronavirus pandemic we have all been aware of the urgent need for nucleic acid testing to identify people currently infected with SARS-CoV-2. The second test that is needed, the serology test, to identify who has had the virus, is much more complex to produce. Dr Andy Lane, commercial director from The Native Antigen Company, discusses adaptive immunity and the production of antigens and antibodies for the creation of immunoassays that can be used for in vitro diagnostics.
What is The Native Antigen Company and what does it do?
The Native Antigen Company was founded in Oxford, UK, in 2010, with the goal of developing native viral and bacterial antigens to support the in vitro diagnostics (IVD) industry. The company was the first to release highly pure Zika virus NS1 antigens for the development of specific diagnostics in 2016, and has since built experience and capabilities to support the research community in pandemic scenarios. In February 2020, the company became one of the firstrecognized suppliers of antigens for SARS-CoV-2 (the virus that causes COVID-19), and has continued to develop a broad and expanding range of coronavirus reagents. Additionally, we offer a wide variety of native and recombinant antigens for over 60 infectious diseases and provide custom and contract services to the life sciences and biotechnology industries.
Our reagents are used by a wide range of researchers working in infectious diseases, but are predominantly sold into two major markets: the IVD industry, who use antigens and antibodies to develop immunoassays for serological diagnosis of infection, and the vaccine industry, who use antigens and antibodies to develop immunoassays for the qualification and quantification of animal and patient vaccine responses in clinical trials.
Briefly, how is immunity generated in response to infection?
It goes without saying that the human immune system is highly complex, but it can generally be broken down into the innate and adaptive immune responses. Innate immunity is our first line of defence. It provides a rapid, but somewhat makeshift response that is largely preoccupied with trying to kill infectious agents from the moment they enter the body, with a broad array of non-specific cells, proteins and biochemicals. While this is ongoing, the innate response alerts the adaptive response. Adaptive immunity (overview in Fig. 1) represents the elite troops of the immune system, which launch an attack that is specifically adapted to the infectious agent using more sophisticated weapons to mediate powerful downstream responses. The hallmark of the adaptive response is clonal expansion, where B and T lymphocytes that are able to recognize a pathogen will be positively selected for to rapidly build their numbers. Once these cells reach significant levels, the body is much better equipped to detect and clear the invading pathogen, and tends to form a long-lasting ‘memory’ of the pathogen to better prepare itself for future encounters.
After some viral infections, we develop lifelong immunity; however, after others we are only protected for a short period of time – why does this difference arise?
There are two major reasons for reinfection by a virus shortly after initial exposure. The first is due to the ability of viruses to mutate, which occurs via the natural accumulation of genetic changes over time (antigenic drift) or recombination of a virus’s genome with a related strain, causing it to rapidly mutate into a novel form (antigenic shift). These processes allow a virus to change its ‘appearance’, such that it is no longer recognizable by our immune system, and makes our previous exposure to the original virus of little use. This is best exemplified by the influenza A virus, which is notorious for mutating its surface proteins (hemagglutinins and neuraminidases) to evade immune recognition, resulting in a perpetual game of cat and mouse that requires the development of new vaccine formulations every flu season.
The second reason for ineffective immune responses is a bit more complex and tends to occur as a result of waning memory cell levels in the host’s immune system following initial infection. However, the cause of short-lived immunity is not entirely clear and largely depends on the virus in question as well as myriad influencing factors, such as genetics, age and previous exposure to pathogens. A very relevant example are the endemic coronaviruses, such as OC43-CoV and 229E-CoV, whose infections may result in only a few months of immunity. A study in the early 90s, for example, showed that exposure with 229E-CoV only one year after initial infection resulted in reinfection in the majority of patients and correlated with declining antibody titres . The reason for the decline in immune memory is not entirely clear but is often attributed to the mild pathogenicity of such viruses eliciting a somewhat lacklustre immune response in the first place.
Given the short-lived immunity of some coronaviruses, COVID-19 immunity has been a hot topic. Most patients have shown quite potent and lasting antibody responses, while some have little-to-no detectable antibodies following infection . While we are not yet sure whether this is an immune phenomenon or an issue of poor assay sensitivity, it will take some time before we are able to truly understand the human body’s response to this disease.
Serology testing is of great importance in clinical diagnostics. When doing serology testing to see if a person has had a disease, what exactly is being detected and how is this usually achieved?
By definition, serology is the scientific examination of blood serum and its components. However, in the context of the clinical diagnosis of infectious disease, it generally refers to the use of immunoassays that measure antigens or antibodies. Immunoassays are found in a wide variety of formats but are best exemplified by the enzyme-linked immunosorbent assay (ELISA), which uses plastic titer plates to bind antigens or antibodies from patient samples and produce a detectable signal.
The second major immunoassay format is the lateral flow assay (LFA), which uses an absorbent pad to absorb an analyte and run it through a series of specific antibodies to produce a detectable signal. These assays have the advantage of being inexpensive and portable and can typically provide results within minutes.
Emerging studies suggest that the serology of SARS-CoV-2 is highly complex and differs significantly from other betacoronaviruses. Antibody responses to SARS-CoV-2 appear to occur later and be of lower titres than are typically observed for viral infections, influencing the way in which assays are designed to diagnose both acute and historic infections. Another important consideration is the potential for antibody cross-reactivity to other co-circulating coronaviruses, requiring close attention to the binding specificity of antigens used.
In the current COVID-19 pandemic, serology testing will be crucial for discovering much about the disease – what will we be hoping to learn from this?
From the outset of the pandemic, the reverse-transcriptase polymerase chain reaction (RT-PCR) has been the predominant means of diagnosing active infection. However, as molecular methods rely on the presence of viral nucleic acids, they are limited to a narrow window during the acute phase of infection when the virus is present in the respiratory tract. This has left a major gap in the ability to detect previous cases and understanding the transmission dynamics of this disease. Antibodies to SARS-CoV-2, however, may last for some time after infection to allow for retrospective diagnosis once patients have recovered. This is particularly useful for multiple reasons.
First, as governments ease lockdown restrictions, high-quality epidemiological data is vital for keeping an eye on temporal and geographical disease dynamics, which will require frequent sampling of antibodies in populations (serosurveys). There is also a clear advantage in using serology tests for diagnosis at the point of care. Unlike high-throughput RT-PCR or ELISAs, LFAs present a highly practical and rapid alternative for acute-phase diagnosis and will be crucial in identifying asymptomatic carriers and infected individuals to ensure they are isolated from the general population.
Another major role of serology is in vaccine testing. So far, there are over 130 vaccine candidates currently in the pipeline . While these vaccines are based on a wide range of platforms, (including mRNA, DNA, nanoparticles, subunits, synthetic peptides and virus-like particles, to name a few), it can be said with near certainty, that a SARS-CoV-2 vaccine will elicit immune responses to the spike protein. However, considering that vaccine-induced anti-spike IgG levels may be indistinguishable from those conferred by natural infection, alternative antigens will be needed to design vaccine-specific assays. These assays will also be very useful in assessing the potential risk of vaccine-induced antibody-dependent enhancement, in which antibodies produced by a vaccine are able to facilitate a more aggressive pathogenesis when a patient gets a real SARS-CoV-2 infection.
How do you go about preparing reagents for a serology test for a new pathogen such as SARSCoV- 2 and why is it important that these reagents are ‘native-like’?
When developing any immunoassay, the most important components are the antigens and antibodies used to design it. The considerations for choosing these reagents are wide-ranging: antigens should include the most appropriate epitopes to facilitate high sensitivity and antibodies should be tested for high affinity to the antigen in question. When considering specificity, it is crucial to ensure than detector antibodies do not bind to the cross-reactive epitopes that are often found on more conserved regions of viral antigens.
To modulate the sensitivity and specificity of an assay, specific portions of a protein can also be used. In the case of SARS-CoV-2, researchers are investigating various different regions of its spike protein for use in immunoassays. The S1 and S2 subunits of the spike are a popular choice for the development of immunoassays as they are highly exposed to the virus’s external environment and can readily induce potent antibody responses. In particular, anti-spike antibodies that bind the receptor-binding domain (RBD) of S1 may be able to neutralize virus by preventing binding with ACE2. The spike RBD functions to mediate cell-surface attachment and internalization by binding human ACE2 receptors. Given RBD’s role in host-cell entry, it is able to elicit highly neutralizing antibody responses and is a popular target for the development of vaccines. The RBD also shows high sequence divergence between other coronavirus spike proteins, making it a popular antigen for the development of sensitive and specific immunoassays. The N-terminal domain of the SARS-CoV-2 spike protein shows the highest sequence variability across the coronavirus family, making it a popular choice of antigen for maximizing the specificity of diagnostic assays.
Given the biosafety implications of handling a live virus, recombinant antigens expressed from other organisms are the go-to for developing assays. However, not all expression systems are born equal. Simple organisms like Escherichia coli are easy to genetically manipulate but lack the necessary post-translational machinery to glycosylate proteins. Incidentally, each SARS-CoV-2 spike trimer contains up to 66 glycan sugars to facilitate folding and mediate viral tropisms, amongst other things. From the perspective of assay development, these glycans constitute many of the key surface epitopes that are recognized by detector antibodies and the use of unglycosylated spike risks the binding of non-specific, cross-reacting antibodies that can reduce diagnostic specificity.
To ensure that spike is produced with its full glycosylation pattern and is properly folded, more complex systems need to be used. At The Native Antigen Company, we use our VirtuE mammalian (HEK293) system that has been developed for the bespoke purpose of expressing high-quality antigens with proper folding and full glycosylation.
What’s your vision for the future for The Native Antigen Company and its collaboration with OXGENE?
After the SARS-CoV-2 genome was published in early January, it was an all-out race to develop and release reagents. After a tremendous effort by our R&D team, we managed to produce our first batch of S1 antigens in early February and began to ship them to our customers around the globe. However, the next challenge was manufacturing capacity. Given the demand from the IVD and vaccine industries, we soon began to struggle in meeting such large demand. Fortunately, we were able to reach out to some manufacturers who could support us with scale production.
Our first partner, OXGENE™ has been using their Protein Machine Technology to develop stable cell lines for the production of spike antigens. Their technology uses a proprietary adenoviral vector to carry SARS-CoV-2 DNA into human cells, where it delivers it to the nucleus for stable integration. From here, cell lines can be cultured en masse to produce large quantities of protein without the inherent limitations in yield of transient expression. Work is still ongoing to optimize expression, but we’re hoping for some positive data in the coming weeks.
Current mass-spectrometry-based strategies will allow us to understand the molecular phenotypes of disease, which will drastically improve the diagnostic power of new clinical tests. In this interview, Professor Cobbaert [head of the Department of Clinical Chemistry and Laboratory Medicine at the Leiden University Medical Center (LUMC), Leiden, The Netherlands] and Dr Van der Burgt (associate professor at the Center for Proteomics and Metabolomics, LUMC) give us their expert opinions on how a strong collaboration between biomarker researchers, clinicians and medical laboratory specialists is necessary to make the development process more efficient. Professor Cobbaert is driven to innovate the field of laboratory medicine: “The clinical lab will change from a care-relevant to a system-relevant cross-sectoral discipline which will greatly affect the development of the entire healthcare system”.
The clinical chemistry lab at the Leiden University Medical Center (LUMC) works closely together with researchers at the Center for Metabolomics and Proteomics (CPM) to develop new bioanalytical tests. The goal is to contribute to Precision Medicine through improved, molecular characterization of health and disease, for the sake of better patient management and patient outcome.
Christa Cobbaert heads the Department of Clinical Chemistry and Laboratory Medicine at LUMC, which encompasses clinical chemistry, hematology, coagulation and blood transfusion.
“In addition to regular patient diagnostics, our department also has responsibility for the hospital-wide central receipt of patient and research specimens. Our department supports research and biobanking from a large variety of clinical groups that want to use our services. Another core task is training and education of lab specialists and medical technicians.
“Some current numbers? Our routine lab works 24/7, we do about 4000 specimens per day, and produce over 4 million tests per year. We have 180 employees, about 140 full time equivalents. The majority are phlebotomists, who collect blood, and medical technologists, who run the analyses. We have an academic staff encompassing multiple laboratory specialists, who are responsible for the lab policy, lab organization, for state-of-the-art test menus, clinical consulting and post-academic training of lab specialists. Head medical technicians, quality control officers, as well as information and communication technology specialists and administrative personnel are a coaching layer between the academics and the operational co-workers.
“Since we are an academic institute, we are responsible for the traineeship of new lab specialists. We also contribute to the education of medical doctors. Teaching future medical doctors about the targeted use of lab diagnostics is key because approximately 70% of medical decisions in hospitals are based on lab results. We further provide teaching contributions in new disciplines such as clinical technology, and contribute to different Masters programmes.”
Dr Yuri van der Burgt is an associate professor at the CPM. “Trained as a chemist, I did a PhD in bioorganic chemistry and moved to the clinical field. At the LUMC I joined pioneering ‘omics’ research for medical care and patient research. For 50% of my time I work for the clinical chemistry lab, and from that position I bridge to the CPM research aiming for improved biomarker translation. CPM has approximately 50 researchers (PhD students postdocs, senior scientists, assistants and associates) and is headed by Manfred Wuhrer. We explore promising biomarkers that are discovered in basic research and aim to verify their potential for translation to the clinic. Mass-spectrometry (MS)-based omics studies have reported a wide variety of biomarkers or signatures, but only a few of these have been translated into a laboratory test. This limited translation is partly due to the lack of standardized protocols, robustness and reproducibility, but more importantly ill-defined or flawed study designs.”
Cobbaert: “We are happy with the cooperation with CPM because it’s very important to have analytical chemists connected to our lab. Once that lab specialists and clinicians have identified unmet clinical needs, analytical chemists support us with the assay development for molecular phenotyping of disease and health using MS-based technology. Together we attempt to bring promising biomarkers from the research field into the clinical arena. We believe that this collaboration should lead to a more robust and effective pipeline for developing medical tests. We also support research from various clinical groups at the LUMC, especially in the domains of Cardiovascular Diseases, Cancer Diagnosis and Kidney Diseases.”
Van der Burgt: “One of the main activities at CPM is the elucidation of modifications on existing protein biomarkers, with emphasis on glycosylation analysis. As we want to make sure that these biomarkers can be of use for the clinic, we do not only report discoveries, but rather aim for further development of our findings into something clinically useful. Therefore we first make an inventory of the unmet needs from the clinicians, and what is actually needed for improved patient care. Hence, the clinical need guides our -omics research. And it is my task to bring these two worlds together. My goal is not just to publish papers on new discoveries, but to contribute to finding more effective solutions: clinically effective, cost effective and safe tests for patient care.”
Cobbaert: “The current pipeline and the current process of financing research is in my perception a wasteful process because there is insufficient attention to the downstream consequences (utility) of the research findings for patient care. Currently the number of papers and citation indices are rewarded, rather than the impact for patient care. Subsidizers should stimulate the translation and implementation of newly discovered biomarkers by making the funding of translation and implementation research inclusive.
“To counteract this inefficient pipeline from discovery to application researchers, clinicians, biostatisticians and lab specialists should collaborate closely. The clinical needs should be the driver of the test development process, rather than the technological push. Once these needs are identified a more informed decision can be made with regard to priorities: ‘This is what we are setting up together and this is where we go for’. The European Federation of Laboratory Medicine (EFLM) Test Evaluation framework provides guidance and encompasses key elements for creating evidence regarding the clinical and cost-effectiveness of new medical tests.
“Our mantra is that our research efforts should lead to precision diagnostics and clinically effective medical tests. In our collaboration with CPM we aim to contribute to better patient management and patient outcome with a targeted approach. As it is essential to add value to clinical pathways and patient management, we need actionable results for better patient care.”
Cobbaert: “We try to educate stakeholders of the biomarkers-medical test pipeline about the usefulness of the Test Evaluation framework for guiding this development process.
“We have asked ourselves: Why is the process from research to application such a wasteful process? What should we do? Last November we organized a precision diagnostics symposium in which we shared our experiences on quantitative proteomics and proposed our solutions [‘Prime time for precision diagnostics driven by unmet clinical needs’ (LUMC, Leiden, The Netherlands, November 2019)]. We also shared our struggles: developing specific molecular tests for proteins is not an easy road. Several barriers had to be alleviated. And that’s difficult to do, sometimes we failed, sometimes we felt that it doesn’t go quick enough. But we all are dedicated to make it a success together.
“Once a medical test is available, and evidence regarding its clinical utility and value has been generated, medical tests have to be implemented in clinical practice, either as a Lab-Developed-Test (rare) or as a Conformité Européene in vitro diagnostic (CE-IVD) test (often). To be successful, clear guidance should be given to doctors regarding its intended use in the clinical care pathway of interest. As a rule of thumb, the average trajectory from promising biomarker to applied medical test in the clinic takes about 10 years.
“In the current curriculum of medical students limited education is given regarding medical test use, notwithstanding the 70% rule (medical decisions are to a large extent based on lab test results). Laboratory specialists have to demonstrate medical leadership by educating physicians on proper test use.
“Collaborations are necessary to innovate laboratory medicine. We all start to understand the need for cooperation between different areas of expertise. A smooth and fruitful interaction between different types of laboratory specialists (e.g. microbiology, pathology, geneticists, immunologists…), researchers and clinicians should help to overcome the old boundaries.”
Collaboration is key
Van der Burgt: “An example of such a collaboration between CPM and clinical chemistry is our work on glycoprotein markers that we recently presented at the symposium on precision diagnostics, ‘Prime time for precision diagnostics driven by unmet clinical needs’ (LUMC, Leiden, The Netherlands, November 2019).
“Structure refinement of the biomarker for prostate cancer, the prostate specific antigen (PSA) demonstrated the importance of glycosylation for further development. We have worked on PSA at the CPM together with the clinical chemistry lab and in that collaborative effort we have seen that we can add extra information on the PSA test readout. Additionally, we aim to discover novel biomarkers for early detection of cancers. We see an enormous worldwide effort there and the result is hundreds, if not thousands, of new markers without any clinical pre-knowledge or knowledge of urgent clinical needs, it was technology-driven.”
Cobbaert: “It should be the opposite, clinical needs and sustainable and affordable health care should be the drivers of the test menu. In that context, our quantitative proteomics based activities for precision diagnostics are becoming more and more appreciated. To make translational research more effective, the funding agencies should also be concerned that the research they support will be applied in the clinical lab and will improve patient care.”
Cobbaert: “In the 20th century, our technology did not enable molecular characterization of disease, at least not in the high-throughput manner that is needed in clinical practice. Now we live in the 21st century and technology and medical insights have evolved. I expect a paradigm shift whereby traditional diagnostic tests will be complemented with precision diagnostic tests which enable Predictive, Preventive, Personalized Medicine, with Participation of the patient.
“As we drill down to the molecular level of health and disease, we should be able to provide more refined diagnoses and treatments. In 10 or 20 years, we may expect to read out a patient’s complete molecular phenotype or ‘proteotype’ and we will be able to monitor changes from a personal baseline.
“To innovate lab medicine and to realize the ambitions for Precision Medicine, we also need to find interoperable information technology (IT)-solutions. To that end, we need strategically thinking people who align the different stakeholders of the test pipeline, strive to improve health and patient care and know how to find advanced technical ,IT and organizational solutions to disclose the billions of data. Standardization of IT and making databases interoperable will be key. Unfortunately, we seem to be very far away from standardized interoperable solutions owing to a very fragmented IT-landscape across and even within health institutions.”
In a new study, a team of researchers led by Charis Eng, M.D., Ph.D., Chair of Cleveland Clinic’s Genomic Medicine Institute, identified a metabolite that may predict whether individuals with PTEN mutations will develop cancer or autism spectrum disorder (ASD).
Germline mutations of the tumour suppressor gene PTEN are associated with a spectrum of rare genetic disorders that increase the risk of certain cancers, cognitive and behavioural deficits, benign growths and tumours (i.e., hamartomas), and macrocephaly. These disorders are referred to collectively as PTEN hamartoma tumour syndrome (PHTS), but clinical manifestations vary greatly among patients and often are difficult to anticipate.
For example, subsets of Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS), two well-defined disorders on the PHTS spectrum, are characterized by either a high risk of certain cancers or ASD. There are functional and structural differences between PTEN mutations associated with ASD and those associated with cancer. However, a biomarker that could proactively determine if a patient with CS/BRRS will develop cancer or ASD has not yet been identified.
Previous studies have established metabolic dysregulation as one of the hallmarks of cancer. Specifically, germline variants in the SDHx genes cause an accumulation of the metabolite succinate, which has been linked to tumorigenesis. Some patients with PTEN mutations have been found to have succinate accumulation despite the lack of SDHx mutations, suggesting that variations in metabolite levels may indicate susceptibility to cancer versus ASD.
To investigate this further, Dr. Eng’s team analyzed the metabolite levels of 511 patients with CS, BRRS, or Cowden-like syndrome compared to controls. The results suggest that certain metabolites are associated with specific mutations and/or clinical features.
In particular, they discovered that decreased levels of fumarate, a metabolite formed from succinate, was more strongly associated with ASD or other developmental disorders compared to cancer in individuals with PTEN mutations. These findings indicate that certain metabolites, such as fumarate, may serve as predictive biomarkers that could distinguish patients who will develop neurodevelopmental disorders from those who will develop cancer.
“By identifying a way to differentiate those with germline PTEN mutations who develop cancer and those who develop autism, this provides clinicians with a MedicalXpress.
NanoPass is sharing its proprietary MicronJet microneedle device with leading vaccine and immunotherapy companies around the world to assist in development of a Covid-19 vaccine.
The NanoPass device targets immune cells of the skin by harnessing the skin’s potent immune system to improve vaccines and/or to dramatically reduce the dose while achieving the same immunity.
“The human skin is our first layer of defence against many infectious diseases,” says Yotam Levin, MD, CEO of NanoPass. “The skin contains specialized Dendritic Cells that process and induce strong immune responses – that’s why microneedle injections enable reduction of vaccine doses by five-fold, thereby reducing overall cost, required capacity and production time. We believe a reliable injection into the skin is critical for successful activation of broad and effective immune responses, which should be explored for most injectable vaccines.”
The company’s technology is supported by more than 55 completed/ongoing clinical studies with various vaccines and vaccine platforms, including H1N1, H5N1 and live attenuated VZV vaccine, that have shown improved immunogenicity and significant dose-sparing. Pre-clinical evidence with mRNA and DNA vaccines showed promising results.
NanoPass has previously supported US CDC in a Phase 3 infant polio vaccination trial; with ITRC on PPD skin testing; in Type 1 Diabetes immunotherapy; and supported NIAID with devices to evaluate immunogenicity of a pandemic flu vaccine; and multiple vaccine pharma.
NanoPass Technologies flagship product, the 0.6 mm MicronJet, is the first true (<1 mm) microneedle to receive FDA clearance as an intradermal delivery device for substances approved for delivery below the surface of the skin. It is supported by extensive clinical data and regulatory approvals in most major markets including the US, Europe, China and Korea.
Grey Wolf Therapeutics, a drug discovery biotechnology company focused on developing first-in-class therapies for immuno- oncology (IO), has completed a £2.5 million ($3.3 million) Series A2 financing round with existing healthcare investors Andera Partners and Canaan.
The new funding will allow the company to accelerate development of therapies targeting endoplasmic reticulum aminopeptidase 2 (ERAP2), following many positive signals of its potential. Funds will also be used to continue to drive the lead endoplasmic reticulum aminopeptidase 1 (ERAP1) modulator program.
Both of Grey Wolf’s novel ERAP approaches are aimed at directly altering tumour cells, illuminating them for attack and destruction by the immune system. The goal is to exploit this increased tumour visibility in monotherapy and to extend the therapeutic benefit of already approved immunotherapies to many more cancers. The company is developing small molecule modulators of ERAP1 and ERAP2, two key proteins in the antigen presentation pathway, to change the antigen repertoire of tumours and thereby increase the number and range of cancer-related antigens, including neoantigens, presented on tumour cells available to engage an immune response. Grey Wolf is expanding efforts around ERAP2 for two reasons. First, clinical data continues to demonstrate that tumours which are more visible to the immune system show improved responses to checkpoint inhibitors. Second, the company has developed unique insight into the targeting of the ERAP enzymes through the lead program ERAP1 and validated the role for ERAP inhibition in modulating the cancer-related antigen repertoire.
“We have continued to generate data showing that modulation of both ERAP pathways drives change to the cancer-related antigen repertoire,” said Tom McCarthy, Executive Chairman and Co-Founder of Grey Wolf Therapeutics. “Data clearly demonstrates that modulation of ERAP2 drives an altogether different change to the antigen repertoire, when compared with ERAP1 modulation, due to ERAP2’s clearly differentiated peptide substrate specificities. With this investment and the prior knowledge base within Grey Wolf we will be able to accelerate the ERAP2 program quickly through optimization, building on our leading position in ERAP disease-related biology.”
Greiner Bio-One is supporting a Swiss Red Cross (SRK) project to modernize the blood donor service and the provision of safe blood supplies for Syrian refugees and the wider public in Lebanon.
Greiner Bio-One has been a project partner of the Swiss Red Cross since May 2019. Due to its extensive and long-term experience, SRK is in a strong position to provide support to several countries in establishing a professional blood donor service. One of these countries is Lebanon.
In addition to promoting quality assurance in the blood donor service, the goal of the Swiss Red Cross is to increase the stock of blood through regular donations. Because safe blood saves lives!
Giving blood is not (yet) necessarily the norm everywhere
In some regions of the world, people often only donate blood for family members so there is therefore not enough available or it needs to be paid for. There is a need to raise awareness here and encourage people to donate blood for others outside their own families. “If somebody needs my blood, I’m there for them,” says Said Mrad, a voluntary Lebanese blood donor. The 26-year-old is giving blood for the fourth time. Thanks to the work of the SRK in cooperation with the Lebanese Red Cross, he now sees it as completely natural to give his blood for other people.
Blood supplies need to be safe
A professional blood donor service not only needs donors but it also needs suitable products and expert knowledge to ensure high quality standards, maximum safety and wide coverage for this vital service. The SRK’s international experience helps the Lebanese Red Cross a great deal as it establishes this valuable service. Greiner Bio-One is supporting this project through its financial contribution, its products and its expertise. www.gbo.com