As the SARS-CoV-2 coronavirus continues to spread throughout the world, the race is on to produce antivirals and vaccines to treat and prevent COVID-19. One potential treatment is the use of human monoclonal antibodies, which are antibodies engineered to target and block specific antigens. A recent study by Wang, C. and colleagues published in Nature Communications showed that human monoclonal antibodies can be used to block SARS-CoV-2 from infecting cells.
In 2012, a 6-year-old girl named Emily Whitehead was battling acute lymphoblastic leukemia (ALL), one of the most common cancers in children. Her cancer was stubborn. After 16 months of chemotherapy, the cancer still would not go into remission. There was nothing else the doctors could do, and she was sent home. She was expected to survive only a few more months. Her parents would not give up and enrolled her into a clinical trial of a new immunotherapy treatment called chimeric antigen receptor (CAR) T cell therapy. She was the first pediatric patient in the program.
Doctors took T cells from Emily’s blood and reprogrammed them in a lab. They essentially sent her T cells to boot camp where they are trained to find cancer cells and destroy them. The reprogrammed T cells were then injected back into her body. A week into treatment, she started getting a fever, the first sign that the treatment was working and her reprogrammed T cells were fighting the cancer. But soon, she got very sick. All of the indicators suggested that she had cytokine release syndrome (CRS)—also known as the cytokine storm. This happens when cytokines are released in response to an infection but the process cannot be turned off. The cytokines continue to attract immune cells to the infection site, causing damage to the patient’s own cells and eventually resulting in acute respiratory distress syndrome (ARDS). (Learn more about the cytokine storm in this blog.)
Emily was soon on a ventilator. Tests showed that she had extremely high levels of one particular cytokine: interleukin-6 (IL-6). Desperate to keep her alive, her doctors gave her a known drug that specifically targets IL-6. The results were dramatic. After one single dose, her fever subsided within hours, and she was taken off the ventilator. On May 2nd, 2012, she woke up from an induced coma—it was her 7th birthday. Her doctors said they have never seen a patient that sick get better that quickly.
One of the biggest outstanding questions of the COVID-19 pandemic is why symptoms vary so much among patients. Some patients have no symptoms at all; some symptoms are mild, while others are extremely severe. Among the more severe cases, a common pattern of disease progression happens like this: A patient gets through the first week with some signs of recovery—then suddenly they rapidly deteriorate. In some cases, they go from needing just a tiny bit of oxygen to requiring a ventilator within 24 hours.
This pattern, often seen in young and otherwise healthy patients, has baffled doctors. What causes these patients to suddenly crash? Research now suggests that the patient’s own immune system may be to blame. It’s called cytokine release syndrome—also known as the “cytokine storm”.
Photo courtesy of National Institute of Allergy and Infectious Diseases
In December 2019, a new disease emerged from a seafood
market in Wuhan, China. People who were infected began experiencing fever, dry
cough, muscle aches and shortness of breath. The disease swept through China
like wildfire and quickly spread overseas to almost every continent. We now
know the virus that caused this disease, SARS-CoV-2, is a member of the severe
acute respiratory syndrome coronavirus, and the disease itself was officially
named COVID-19. According to the Johns Hopkins University Coronavirus Resource Center,
there are 877,422 confirmed cases of COVID-19 worldwide, and 43,537 total
deaths at the publication of this blog. Those numbers are only expected to
increase over the next few weeks.
In this moment of crisis, scientists all around the world are desperately trying to find ways to treat and prevent the disease. One strategy for preventing the spread of the virus is to block its entry into human cells. But first we need to understand how SARS-CoV-2 enters human cells. A research group at the German Primate Center led by Dr. Stefan Pohlmann provides some answers in a recent publication in Cell.
Snakebite is a serious public health issue in many tropical countries. Every year, roughly 2 million cases of poisoning from snakebites occur, and more than 100,000 people die. Snake venom is extremely complex, containing a cocktail of chemicals, many of which are undefined. This complicates the development of new therapeutics for treating snakebite.
Antivenom is the most effective treatment for snakebites,
but its production is complex and dangerous. It involves manually milking the
venom from different species of live snakes, then injecting small doses of the
venom into animals (mostly horses) to stimulate an immune response. After a
period of time, antibodies form in the animal’s blood, which is purified for
use as antivenom.
But what if we could produce snake venom in the lab, instead
of using live snakes? Recently, a group from the Netherlands did just that by
growing organoids derived from snake venom glands.
Last year, on Promega’s 40th anniversary, we received a generous gift from a friend in the industry: Eppendorf. That gift was an exchange program. The teenage child of any Promega employee was given the opportunity to visit an Eppendorf family in another country, and in return host the Eppendorf family’s child in their home. The goal was for both children to experience another culture and build a relationship with each other.
In 2019, 11 Promega children bid good-bye to their parents,
hopped on a plane, and flew to Germany. There they would stay for three weeks with
a family they’ve never met. For all involved, it proved to be a valuable and
positive learning opportunity. Here are a few takeaways from their experience:
We rely on insulin supplied by our pancreas at the right dose and at the right time to control our blood glucose levels and energy storage. Insulin works by regulating the energy usage of various cell types in the body. When this process goes awry, it can cause diabetes.
There are two types of diabetes, defined by how insulin is
dysregulated. In Type 1 Diabetes (T1D), the pancreas produces too little
insulin. Patients need to give themselves insulin in order to respond to
glucose in the diet. In Type 2 Diabetes (T2D), patients do not respond well to
the insulin produced in their body. Therefore, they need to give themselves
more to avoid hyperglycemia (high blood glucose).
Our innate immune system was meant to do good. Up until a
century ago, most humans died from infectious diseases like diarrhea,
tuberculosis and meningitis. Over millions of years, our immune system has
evolved to fight these life-threatening infections from pathogens. As a result,
we have developed a highly efficient response to these tiny invaders. But it
seems that our immune system may be turning against us.
You may have heard that antioxidants are good for you, but
in some cases, they can be harmful. In 2014, a study led by Dr. Martin Bergo at
the Karolinska Institutet in Sweden showed that antioxidant supplements, such
as vitamin E, accelerated tumor growth. This sparked much controversy as it was
previously believed that antioxidants prevented tumor progression.
Since then, more evidence suggest that antioxidants indeed
promote tumor progression by reducing reactive oxygen species (ROS) that block
tumor growth. In 2019, the same group published a follow-up study to further
explain how antioxidants promote lung cancer metastasis.
In recent years, great advances have been made in the field of immunotherapy to treat cancer. One of the most promising treatments involves engineering immune cells to express chimeric antigen receptors (CAR). These receptors are carefully designed to recognize antigens expressed on the surface of tumor cells. Once the target is recognized, the CAR-engineered immune cells can attack and kill the tumor cells. CAR T cells have been successfully used to treat certain blood cancers—three CAR T therapies for lymphoma and leukemia have gained US FDA approval. In these cases, T cells were taken from individual patients, grown and genetically-altered in the lab, then reintroduced into the same patient. Continue reading “Evaluating CAR NK Immunotherapy in Patient-Derived Colorectal Organoids”
