In the Literature

Blogs about published peer-reviewed scientific studies.

HPK1 Identified as Emerging Immuno-oncology Drug Target

Posted on by Michele Arduengo

Antibody-based immune checkpoint inhibitors remain a major focus of immuno-oncology drug research and development efforts because of their recent success in providing long-term anti-tumor responses. However, the range of response of different tumor types to these drugs is hugely varied. Small molecule kinase inhibitors that block signaling pathways involved in regulation of tumor immunity at multiple points in the “cancer immunity cycle” may provide alternate, effective therapeutics. One kinase that may be a target for such small molecule inhibitors is Hematopoietic Progenitor Kinase 1 or HPK1; the potential of this kinase as a therapeutic target was reviewed by Sawasdikosol and Burakoff (1). HPK1, also known as MAP4K1, is a member of the MAP kinase protein kinase family that negatively regulates signal transduction in T-cells, B-cells and dendritic cells of the immune system.

Artist rendering of what target engagement might look like for kinases like HPK1.
NanoBRET™ Target Engagement Assay (artist rendering)
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COVID-19 Therapies: Are We There Yet?

Posted on by Ken Doyle

A year after COVID-19 was declared a pandemic, collaborative efforts among pharma/biotech and academic researchers have led to remarkable progress in vaccine development. These efforts include novel mRNA vaccine technology, as well as more conventional approaches using adenoviral vectors. While vaccine deployment understandably has captured the spotlight in the fight against COVID-19, there remains an urgent need to develop therapeutic agents directed against SARS-CoV-2.

COVID-19 therapeutic drugs

In the March 12 issue of Science, an editorial by Dr. Francis Collins, director of the U.S. National Institutes of Health (NIH), examines lessons learned over the past 12 months (1). Collins points out that many clinical trials of potential therapeutics were not designed to suit a public health emergency. Some were poorly designed or underpowered, yet they received considerable publicity—as was the case with hydroxychloroquine. Collins advises developing antiviral agents targeted at all major known classes of pathogens, to head off the next potential pandemic before it becomes one. A news feature in the same issue discusses the current state of coronavirus drug development (2).

The present crop of drug candidates is remarkably diverse, including repurposed drugs that were originally developed to treat diseases quite different from COVID-19. Typically, however, the mainstream candidates belong to two broad classes: small-molecule antiviral agents and large-molecule monoclonal antibodies (mAbs).

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Fighting Plant Pathogens Worldwide with the Maxwell® RSC PureFood GMO and Authentication Kit

Posted on by Ken Doyle

Among the one trillion or so species that share space on our planet, complex relationships have emerged over time. Such relationships, in which two or more species closely interact, are collectively termed symbiosis. Although it’s commonly assumed that symbiotic relationships are mutually beneficial, this example constitutes only one type of symbiosis (known as mutualism). The traditional predator-prey relationship, clearly a one-sided arrangement, is also an example of symbiosis.

Olive trees in Italy are being affected by the plant pathogen Xylella fastidiosa

The sheer diversity of microbial species has led to the development of many well-characterized relationships with plants and animals. Perhaps the best-known example of mutualism in this context is the process of nitrogen fixation. In this process, various types of bacteria that live in water, soil or root nodules convert atmospheric nitrogen into forms that are readily used by plants. On the other hand, some types of bacteria-plant relationships are parasitic: the bacteria rely on the plant for survival but end up damaging their host. Parasitic relationships can have devastating ecological and economic consequences when they affect food crops.

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A Bioluminescent Biosensor for Detection of Mycotoxins in Food

Posted on by Johanna Lee

3D artistic rendering of a NanoBiT assay, the system used in this study for detection of mycotoxins in food

Food contamination is a serious global health issue. According to the WHO, an estimated 600 million, almost 1 in 10 people globally, suffer from illness after eating contaminated food—and 420,000 die. Developing new technologies for more effective testing of food contaminants can help reduce that number and improve public health.

A recent application of bioluminescent technology could change the way we test for mycotoxins in the future. Dr. Jae-Hyuk Yu, Professor of Bacteriology at the University of Wisconsin-Madison, and his then graduate student, Dr. Tawfiq Alsulami, collaborated with Promega to develop a bioluminescent biosensor that enables simple and rapid detection of mycotoxins in food samples.

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Finding Signs of Cancer in Dinosaur Fossils

Posted on by Sara Klink
Centrosaurus is a herbivorous Ceratopsian dinosaur that lived in Canada in the Cretaceous Period. A recent report describes the characterization of cancer in a Centrosaurus dinosaur fossil.
Centrosaurus is a herbivorous Ceratopsian dinosaur that lived in Canada in the Cretaceous Period.

Did dinosaurs get cancer? That isn’t an easy question to answer. Finding and diagnosing cancer in dinosaur fossils has proven difficult. Any soft tissue, the typical location of tumors, has degraded over the millennia. Fossilized bones millions of years old are subject to wear and tear, making it hard to distinguish bone damage from possible pathology. By using the knowledge and expertise gained from diagnosing cancer in humans, a team reported in The Lancet Oncology that they found the first known case of osteosarcoma in a lower leg bone from a horned dinosaur found in southern Alberta, Canada.

This case of bone cancer discovered in a specimen of Centrosaurus apertus found in the Canadian Dinosaur Park Formation was confirmed by examining the bone surface along with radiographic and histological analysis. The 77–75.5-million-year-old case was compared to both a normal C. apertus fibula from the Oldman formation also in southern Alberta, Canada, as well as a human fibula with an osteosarcoma.

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Characterizing DNA Repair Proteins with Cell-Free Protein Expression

Posted on by Gary Kobs
Cell-free protein expression helped researchers take a closer look at DNA double-strand breaks.

A new article in Nature Scientific Reports answers open questions about TOPBP1, a protein involved in repairing DNA double-strand breaks (DSBs). The study used cell-free protein expression and a unique DSB system to identify domains that were important for activation of a protein kinase.

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Ten Things to Know about Inducible T Cell Co-stimulators (ICOS)

Posted on by Kari Kenefick

The term ICOS —inducible T cell co-stimulators— has been prominent in my work as a science writer at Promega, recently. Here is a brief look at ICOS, how it works, and how it can be used in therapeutics research and development.

T cells do amazing things, like driving or blocking production of B cells and their related antibodies and antibody maturation, and they are the primary drivers of innate immunity. T cells have a variety of surface molecules, the primary and omnipresent T cell receptor (TCR), as well as CD3.

Schematic diagram of a T cell receptor TCR. The TCR interacts with ICOS in the immune response.

In the past 15 years or so, researchers have identified other, inducible receptors on T cells. These receptors appear when T cells are stimulated, enabling interactions with other cell types. The following information is summarized from a Frontiers in Immunology review by Wikenheiser et al.

What is ICOS (inducible T cell co-stimulators)?

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Intranasal COVID-19 Vaccines: What the Nose Knows

Posted on by Ken Doyle

COVID-19 vaccine distribution efforts are underway in several countries. Recently, the Serum Institute of India celebrated the nationwide rollout of its Covishield vaccine, kicking off the country’s largest ever vaccination program. Meanwhile, many other vaccines against the coronavirus that causes COVID-19 are in either preclinical studies or clinical trials. At present, 19 vaccine candidates are in Phase 3 clinical trials, while 8 vaccines have been granted emergency use authorization (EUA) in at least one country.

intranasal covid-19 vaccine coronavirus

In the US, mRNA vaccines from Pfizer/BioNTech and Moderna are in distribution. Adenoviral vector vaccines authorized for distribution include Oxford/AstraZeneca AZD1222 in the UK (Covishield in India) and Gamaleya Sputnik V in Russia. A third type of vaccine consists of inactivated coronavirus particles, such as those developed by Sinopharm and Sinovac in China.

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Adenoviral Vector Vaccines for COVID-19: A New Hope?

Posted on by Ken Doyle

The global war against the coronavirus that causes COVID-19 rages on, spearheaded by efforts to develop effective and safe vaccines. At the time of writing, over 100 COVID-19 vaccine clinical trials were listed in the clinicaltrials.gov database. Recent attention has focused on mRNA vaccines developed by Pfizer/BioNTech and Moderna. If licensed, they would become the first mRNA vaccines for human use.

Other vaccine development efforts are relying on more conventional techniques—using an adenoviral vector to deliver a DNA molecule that encodes the SARS-CoV-2 spike (S) protein. Examples of these adenoviral vector vaccines include the vaccines from Oxford University/AstraZeneca (the UK), Cansino Biologics (China), Sputnik V (Russia) and Janssen Pharmaceuticals/Johnson & Johnson (the Netherlands and USA).

sars-cov-2 coronavirus covid-19 infection with antibodies from a vaccine attacking the virus; several vaccines are in development including adenoviral vector vaccines
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mRNA Vaccines for COVID-19: The Promise and Pitfalls

Posted on by Ken Doyle

Updated 8/25/2021, 4/29/2024

Multiple battles are being fought in the war against the SARS-CoV-2 coronavirus that causes COVID-19. Currently, there are nearly 5,000 clinical trials listed in the World Health Organization (WHO) database, either underway or in the recruiting stage, for vaccines and antiviral drugs. The Moderna mRNA vaccine and Janssen vaccine received emergency use authorization (EUA) from the Food and Drug Administration (FDA) and have since been fully approved; the Pfizer-BioNTech Vaccine (marketed as Comiraty) received FDA approval in August 2021.

mrna vaccines and coronavirus covid-19

Both the Moderna vaccine and Comiraty are mRNA-based, as opposed to most conventional vaccines against established diseases that are protein-based. Typically, the key ingredient in viral vaccines is either part of an inactivated virus, or one or more expressed proteins (antigens) that are a part of the virus. These protein antigens are responsible for eliciting an immune response that will fight future infection by the actual virus. Another approach is to use a replication-deficient viral vector (such as adenovirus) to deliver the gene encoding the antigen into human cells. This method was used for the coronavirus vaccine developed by Oxford University in collaboration with AstraZeneca; phase 3 interim data were announced on the heels of the Pfizer/BioNTech and Moderna announcements. All three vaccines target the SARS-CoV-2 spike protein, because it is the key that unlocks a path of entry into the host cell.

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