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Researchers identify the switch that activates programmed death of cancer cells.

The UC Davis Comprehensive Cancer Center has conducted an in-depth research study. The focus was to activate programmed death of cancer cells. A crucial epitope has been identified on the CD95 receptor, and it triggers the death of cells. An epitope is a section of protein that activates the larger protein. As cell death can now be programmed, cancer treatment methods have become effective.

In molecular biology, CD95 receptors are known as Fas and death receptors. These receptors are proteins present in cell membrane. They evoke self-destruction of cells by releasing a signal. This happens when CD95 receptors are activated. By modulating the activity of Fas, researchers extended its benefits to CAR T-cell therapy. This was effective in destroying solid tumours of ovarian cancer.

Managing cancer with better therapies

The conventional method of treating cancer includes chemotherapy, radiotherapy, and surgery. In cases where cancer is diagnosed at an initial stage, these methods are effective. However, cancer cases may relapse, especially when they are therapy-resistant. Recently, CAR T-cell immunotherapy and an immune checkpoint receptor molecule have shown to activate antibodies, and thus they are promising candidates that destroy the cycle of cancerous growth.

These immunotherapeutic agents are effective against only few types of cancer cells, such as ovarian cancer, breast cancer, lung cancer, and pancreatic cancer. In CAR T-cell therapy, researchers engineer the specific type of immune cells, that is, T cells. They graft these cells on a specific antibody that targets specific tumours. The grafted T cells are quite effective in battling leukaemia and other types of blood cancer.

The engineered T cells have not been effective in combating solid tumours; the microenvironment of these tumours drives off T cells and other immune cells. Thus, they cannot provide a therapeutic effect to solid tumours. Although the immune receptor activates antibodies, the T cells cannot infiltrate without additional spaces.

The activity of death receptors

Now, let us understand the activity of death receptors. Through targeted therapy, we can trigger them into programming cell death of tumours. Thus, chemotherapeutic drugs should be such that they induce the activity of death receptors. Many pharmaceutical companies have been slightly successful in targeting the death receptor-5. But the clinical trials of Fas agonists have failed.

Developing the right target

The activity of immune cells is effectively regulated by Fas. However, researchers have proposed that cancer cells can be targeted selectively if they identify the correct epitope. After identifying the targeted epitope, researchers of this study have designed a new type of antibodies. These antibodies show selectivity while binding and activating Fas. With this strategy, specific tumor cells can be destroyed.

 

 

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In severe cases of COVID-19, autoantibodies cause havoc and even death

 

It is a well-known fact that the pandemic of COVID-19 can be controlled only by boosting the production of antibodies in the immune system of patients. However, a recent article in Nature magazine reports otherwise. According to scientists at Yale University, the immune system of patients with severe COVID-19 is impaired significantly and boosting the production of antibodies cannot really control the illness.

Diseases like lupus and rheumatoid arthritis are autoimmune disorders, which are treated by boosting the production of autoantibodies. These antibodies interact and target damaged tissues associated with autoimmune diseases. In patients afflicted with COVID-19, autoantibodies target multiple organ systems that are otherwise healthy. This means that healthy tissues in the brain, liver, and gastrointestinal tract are attacked by autoantibodies. Moreover, they also target blood vessels and platelets in the bloodstream. This implies that the severity of COVID-19 is directly proportional to the number of detected autoantibodies.

Scientists at Yale University also found out that these autoantibodies attack many proteins in the immune system, that is, proteins that otherwise effectively fight infections are damaged by autoantibodies. Therefore, the situation is like a double-edged sword in patients with severe COVID-19 infection. In general, antibodies are effective in combating infection, but when COVID-19 infection is severe, patients develop autoantibodies. These autoantibodies attack multiple types of cells and tissues.

In most cases of COVID-19, the infection became severe and led to the production of autoantibodies, which are antibodies that caused extensive damage. However, it must be noted that in most severe cases of COVID-19, patients already had a pre-existing disease that caused the production of autoantibodies. The observation was done after testing mice with pre-existing autoimmune disorders and who had developed COVID-19 infection. Such mice had a large concentration of autoantibodies. Such kind of sickly mice were more likely to succumb to COVID-19 infection as there is no effective cure till date.

Autoantibodies are also called rogue antibodies and are believed to be existing for a long period of time in patients with pre-existing autoimmune disorders. When such patients contracted COVID-19 infection, they developed severe form of the disease that could not be tackled with existing medications and injections. The medical symptoms of COVID-19 became severe and long lasting in these patients. In other words, the virus became a legacy in the bodies of these patients. Therefore, all patients with autoimmune disorder should immediately be vaccinated to prevent more cases of severe COVID-19.

In patients with autoimmune disorder, autoantibodies are produced even at a mild stage of COVID-19 infection. The study was conducted by an esteemed team of scientists and physicians working at Yale University. In their clinical practice, they made concerted efforts to tackle COVID-19 infection: they screened blood samples of 194 patients with COVID-19 infection; the extent of severity was different in different patients. Nevertheless, autoantibodies were detected in all the blood samples of these patients.

Yale scientists developed a novel technology to detect the extent of damage caused by autoantibodies to proteins of the immune system. The technology was named Rapid Extracellular Antigen Profiling (REAP), and it explored the interaction of autoantibodies with approximately 3,000 proteins of the human body.

The scientists at Yale believe that the study’s findings may be used to develop novel strategies to combat or even prevent the damage caused by autoantibodies in patients with severe infection of COVID-19. Moreover, REAP technology is not just restricted to measuring the response of autoantibodies to COVID-19 infection.

The technology can be used to determine the damage caused by autoantibodies in patients with many types of autoimmune disorders and chronic diseases. These scientists are now exploring whether the technology can be used to determine the damage caused by autoantibodies in cancer patients and in patients with neurological disorders.